FIRST VIENNA SHOCK FORUM Part A: Pathophysiological Role of Mediators and Mediator Inhibitors in Shock Proceedings of the First Vienna Shock Forum held May 1-3,1986

Editors Günther Schlag Heinz Redl Ludwig Boltzmann Institute for Experimental Traumatology Vienna, Austria

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Library of Congress Cataloging-in-Publication Data Vienna Shock Forum (Ist: 1986) First Vienna Shock Forum. (Progress in clinical and biological research ; 236) Contents: pt. A. Pathophysiological role of mediators and mediator inhibitors in shock pt. B. Monitoring and treatment of shock. Includes bibliographies and index. 1. Shock—Congresses. I. Schlag, Günther. II. Redl, Heinz. III. Title. IV. Series: Progress in clinical and biological research ; v. 236. [DNLM: 1. Monitoring, Physiologie—congresses. 2. Shock—physiopathology— congresses. 3. Shock—therapy—congresses. Wl PR668E v.236 / QZ 140 V662 1987f] RB150.S5V54 1987 616'.047 87-3921 ISBN 0-8451-5086-3 (set) ISBN 0-8451-0196-X (pt. A) ISBN 0-8451-0197-8 (pt. B) Contents Contributors xiii Contents of Part B xxiii Preface Günther Schlag and Heinz Redl xxv 1. THE PATHOPHYSIOLOGICAL ROLE OF MEDIATORS AND INHIBITORS THEREOF IN SHOCK 1.1. Complement—Granulocytes Complement Activity in Shock Mats Heideman and Anders Bengtson 3 Inflammatory Mediators in Patients With Ischemic Limbs Anders Bengtson, Pia Holmberg, and Mats Heideman 11 Granulocytes as Mediators of Tissue Injury in Shock: Therapeutic Implications Dale E. Hammerschmidt and Gregory M. Vercellotti 19 Role of Fibrin-Neutrophil Interactions in Lung Vascular Injury Asrar B. Malik 33 Quantitative Estimation of Leukostasis in the Posttraumatic Lung—Canine and Human Autopsy Data Heinz Redl, Hans P. Dinges, and Günther Schlag 43 Whole Body Inflammation in Trauma Patients; an Autopsy Study Hans K.S. Nuytinck, Xavier J.M.W. Offermans, Karel Kubat, and R. Jan A. Goris 55 White Cells in Shock Ischemia David H. Lewis, Anders Gidlöf, Kristina E-dr. Behm, Maj-Britt Bengtsson, and Angela Menschik 63 Neutrophil Protease Enzymes and Oxygen Free Radicals as Mediators of Pulmonary Membrane Damage Stephen Westaby 75 1.2. Proteases Studies on Shock Düring Extracorporeal Circulation Düring Aorto-Coronary Bypass Operations Wolfgang Heller, Günther Fuhrer, Hans-Eberhard Hoffmeister, and Michael J. Gallimore 87 Sii viii / Contents Biochemical Monitoring of the Lung Düring and After Extracorporeal Circulation Geza Horpacsy, Werner Hügel, Hugo Müller, and Alfred Geißler 95 Effect of Elevated Cl-Esterase Inhibitor Levels on Elastase Release In Vitro—A Proposed Model of Shock (ECC) Wolfgang Heller, Günther Fuhrer, Susanne Hoberg, Hans-Eberhard Hoffmeister, and Anton Philapitsch 107 Granulocyte Elastase and White Cell Counts in Septic Pigs M. Siebeck, H. Hoffmann, and R. Geiger 115 Influence of the Lysosomal Elastase Inhibitor Eglin on the Development of Interstitial Lung Edema in E. coli Bacteremia in Pigs H.F. Welter, M. Siebeck, O. Thetter, and M. Jochum 121 Evaluation of the Kinin-Induced Pathomechanisms in the Development of ARDS by Kallikrein Inhibition In Vivo O. Thetter, H. Hoffmann, M. Siebeck, H.F. Welter, and H. Fritz 127 Local Activation of the Kallikrein-Kinin System in the Lung Following E. coli Sepsis in Sheep Svenerik Andreasson, Lennart Smith, Ansgar O. Aasen, and Bo Risberg .... 133 Cl-Esterase Inhibitor in Early Septicemia M. Siebeck, A. Philapitsch, H. Wiesinger, and H.F. Welter 141 Anti-Proteases in Endotoxemia Daniel L. Traber 149 Effect of Aprotinin and Cl-Esterase Inhibitor on Activation of the Plasma Kallikrein-Kinin System In Vivo H. Hoffmann, M. Siebeck, O. Thetter, E. Fink, and A. Philapitsch 159 Cellular Effects of Aprotinin Heinz Redl, Anna Schiesser, Eva Paul, Claudia Wilfing, and Günther Schlag . 165 Feasibility Study of Very High Aprotinin Dosage in Polytrauma Patients C. Clasen, M. Jochum, and W. Mueller-Esterl 175 Hemodynamics and Proteolysis in Experimental Trypsin Induced Shock Froye Naess, Johan Pillgram-Larsen, Tom E. Ruud, Jan O. Stadaas, and Ansgar O. Aasen 185 Protease Inhibitor Infusion Improves Survival Rate and Hemodynamics in Experimental Pancreatic Shock Tom E. Ruud, Ansgar O. Aasen, Johan Pillgram-Larsen, and Jan O. Stadaas 193 Biologie Availability of Injected or Aerosolized Aiphai Proteinase Inhibitor R.M. Smith, R.G. Spragg, and K.M. Moser 203 Multitherapy: A New Treatment Regimen in Endotoxemia Ansgar O. Aasen, Tom E. Ruud, Johan Pillgram-Larsen, and Jan O. Stadaas 211 Hemodynamic Consequences of Multitherapy Pretreatment in Experimental Endotoxemia J. Pillgram-Larsen, T.E. Ruud, J.O. Stadaas, and A.O. Aasen 227 Contents / ix 1.3 Oxygen Radicals—Lipid Peroxidation Oxygen Radicals and Lipid Peroxidation in Experimental Shock Gerd O. Till and Peter A. Ward 235 Cytotoxic Lipid Peroxidation Products Hermann Esterbauer, Ernst Koller, Peter Heckenast, Robert Moser, and Claude Celotto 245 Oxidant Injury of Cultured Cells: Biochemical Consequences R.G. Spragg, I.U. Schraufstatter, P.A. Hyslop, D.B. Hinshaw, and CG. Cochrane 253 Oxygen Radicals Scavenging in Prophylaxis and Treatment of Experimental Shock G.P. Novelli, P. Angiolini, G. Martini, and R. Tani 259 Antioxidant Drugs and Shock Therapy O. Ortolani, M. Biasiucci, A. Trebbi, M. Cianciulli, and R. Cuocolo 271 Protection by Ebselen Against Endotoxin Shock in Rats or Mice Sensitized by Galactosamine K.-H. Konz, G. Tiegs, and A. Wendel 281 1.4. , Leukotriene«, and Platelet Activation Factor Activation of the Pulmonary Arachidonic Acid System and Its Consequences for Hemodynamics and Heinz Neuhof, Werner Seeger, and Norbert Suttorp 289 Leukotriene« as Mediators in Endotoxin Shock and Tissue Trauma Dietrich Keppler, Wolfgang Hagmann, and Claudio Denzlinger 301 Generation of Leukotriene« in Polytraumatic Patients With Adult Respiratory Distress Syndrome (ARDS) J. Knöller, W. Schönfeld, T. Joka, J. Sturm, and W. König 311 On the Pathogenesis of Adult Respiratory Distress Syndrome—The Role of Anaphylatoxins, Leukotrienes and Platelet Activating Factor U. Pison, K.P. Schmit-Neuerburg, and W. König 317 Increased Hemodynamic and Survival With Endotoxin and Septic Shock With Ibuprofen Treatment Roger C. Bone, Elizabeth Rogers Jacobs, and Frank J. Wilson, Jr 327 Effect of Ibuprofen on Components of an Acute Systemic Inflammatory Response Evoked by Intravenous Endotoxin Administration in the Conscious Sheep Gary J. Jesmok, Frederick Aono, Janet Simpson, and Julian Borgia 333 Effect of the Nonsteroidal Antiinflammatory Agent BW755C in Rat and Sheep Endotoxemia Soheyl Bahrami, Fred Mihm, Martin Thurnher, Christa Vogl, Anna Schiesser, Heinz Redl, and Günther Schlag 347 x / Contents Effectiveness of Ei in Adult Respiratory Distress Syndrome William C. Shoemaker 361 Efficiency of Prostacyclin in Rabbit Endotoxin Shock Heinrich Ditter, Peter Röttger, Reinhard Voss, and F. Reinhard Matthias . . . 369 1.5 Endotoxin Endotoxin: The Causative Factor of Mediator Release Düring Sepsis Daniel L. Traber 377 Endotoxin Shock Model in the Dog: A Reevaluation Jean-Louis Vincent, Marc Domb, Pascal Luypaert, Corinne De Boelpaepe, Philippe Van der Linden, and Serge Blecic 393 Perturbation of Transmembrane Signaling Mechanisms in Acute and Chronic Endotoxemia Judy A. Spitzer, Elena R. Turco, Ion V. Deaciuc, and Bryan L. Roth 401 Endotoxin-Induced Generation of Oxygen Free Radicals in Freshly Drawn Human Blood Hubert Reichle, Dagmar Langner, Peter Wendt, and Günther Blümel 419 Inhibition of Lipopolysaccharide-Mediated Activation of Neutrophils With Monosaccharide Derivatives of Lipid A Charles Lam, Elizabeth Basalka, Eberhard Schütze, and Hubert Walzl 427 2. RESULTS OF MEDIATOR RELEASE Physiologie and Metabolie Correlations in Human Septic Shock John H. Siegel 439 Multisystem Organ Failure Hans-Peter Schuster 459 Changes in Metabolie Control in Injury and Sepsis Rod A. Little and Keith N. Frayn 463 Catecholamines in the Serum of Multiple Trauma Patients—Mediators of ARDS? P. Sefrin 477 Increased Systemic Microvascular Permeability in Septic Shock A.B. Johan Groeneveld and Lambertus G. Thijs 487 Differences in Regional Oxygen Supply, Oxygen Consumption and Blood Flow Düring the Onset of E. coli Sepsis G.I.J.M. Beerthuizen, R.J.A. Goris, H.J.M. Beijer, and G.A. Charbon .... 495 Vascular Perfusion of the Ischemic Small Intestine Miklös Juhäsz, Jänos Hamar, Läszlö Dezsi, Erzsebet Feher, and Joachim Lutz 503 Reaction Pattern of Alveolar Cells in the Posttraumatic Lung Failure Theo Joka, Udo Obertacke, Wolfgang Schönfeld, Susanne Oberste-Beulmann, Ulrich Pison, Ernst Kreuzfelder, Marianne Jochum, and Gerda Zilow 509 Contents / xi Phospholipid Lung Profile in Adult Respiratory Distress Syndrome— Evidence for Surfactant Abnormality U. Pison, E. Gono, T. Joka, and U. Obertacke 517 Wound Inflammatory Mediators and Multisystem Organ Failure Robert H. Demling 525 Burn Shock and Its Resuscitation 3Davi. THd EN HEAR. HerndonT A, SJame A SPECIAs G. HiltonL TARGE, DanieTl LORGA. TraberN , IanN dSHOC RoberKt E. Barrow. 539 Evaluation of Heart Performance With Special Emphasis on Severe Hemodynamic Changes Düring Hypovolemic-Traumatic Shock Peter Krösl and Günther Schlag 561 Myocardial Dysfunction in Sepsis John J. Spitzer, Lani W. Smith, Edmund C. Burke, and Kathleen H. McDonough 573 Studies on Low Molecular Weight Inotropic Plasma Substances in Prolonged Hypovolemic Traumatic Shock Seth Hallström, Christa Vogl, Peter Krösl, Heinz Redl, and Günther Schlag . . 591 Cardiodepressant and Cardiostimulant Factors in Shock 599 SandorNagy Release of Myocardial Depressant Factor (MDF) Düring Cardiopulmonary Bypass (CPB): Influence of Corticosteroids (Methylprednisolone) and Protease Inhibitor (Aprotinin) Farag I. Coraim, Günther Laufer, Wilfried Ilias, Gregor Wollenek, 611 and Ernst Wolner Endogenous Nickel Release in Injured Patients: A Possible Cause of Myocardial Damage Kornel Szabö, Istvän Balogh, and Anna Gergely 621 Heart Rate Düring Hypotensive Central Hypovolemia Before and After Atropine in Man Käre Sander-Jensen, Jesper Mehlsen, Carsten Stadeager, Peter Bie, and Jorgen Warberg 629 Antioxidant Protection Against Free Radicals Mediated Myocardial Injury Elizabeth Roth, Bela Török, William Bär, and Susan Pollak 633 Index 641

Contributors Ansgar O. Aasen, Surgical Department, G. I. J. M. Beerthuizen, Department Ullevaal Hospital, University of Oslo, of General Surgery, University Hospital 0407 Oslo 4, Norway St. Radboud, Nijmegen, The [133,185,193,211,227] Netherlands [495] Svenerik Andreasson, Department of Kristina E-dr. Behm, Clinical Anesthesiology, East Hospital, Research Center, University Hospital, Göteborg, Sweden [133] Linköping, Sweden [63] P. Angiolini, Institute of Anesthesiology H. J. M. Beyer, Experimental and Intensive Therapy, University Laboratory for Peripheral Circulation, Policlinico di Careggi, 50134 Florence, University Hospital Utrecht, Utrecht, Italy [259] The Netherlands [495] Frederick Aono, Department of Life Anders Bengtson, Department of Sciences, Travenol Laboratories, Inc., Anesthesiology, Sahlgren's Hospital, Round Lake, IL 60073 [333] Göteborg, Sweden [3,11] Soheyl Bahrami, Ludwig Boltzmann Maj-Britt Bengtsson, Clinical Research Institute for Experimental Center, University Hospital, Linköping, Traumatology, Vienna, Austria [347] Sweden [63] Istvän Balogh, Institute of Forensic M. Biasiucci, Intensive Care Medicine, Semmelweiss Medical Department, II Faculty of Medicine, University, Budapest, Hungary 1082 University of Naples, Napoli, Italy [621] [271] Peter Bie, Department of Medical William Bär, Material Chemical Physiology, Panum Institute and Works, Budapest, Hungary 1734 [633] Hvidovre Hospital, University of Robert E. Barrow, Department of Copenhagen, Copenhagen, Denmark Research, Shriners Burns Institute, [629] Galveston, TX 77550 [539] Serge Bleck, Department of Intensive Elizabeth Basalka, Sandoz Care, Erasme University Hospital, Free Forschungsinstitut, A-1235 Vienna, University of Brüssels, Brüssels, Austria [427] Belgiüm [393]

The numbers in brackets are the opening page numbers of the contributors' articles. xiii xiv / Contributors Günther Blümel, Department of Corinne De Boelpaepe, Department of Experimental Surgery, Technical Intensive Care, Erasme University University, 8000 Munich 80, Federal Hospital, Free University of Brüssels, Republic of Germany [419] Brüssels, Belgium [393] Roger C. Bone, Rush-Presbyterian- Robert H. Demling, Longwood Area St. Luke's Medical Center, Chicago, Trauma Center, Harvard Medical Dlinois 60612 [327] School, Boston, MA 02115 [525] Julian Borgia, Department of Life Sciences, Travenol Laboratories, Inc., Claudio Denzlingen Biochemisches Round Lake, IL 60073 [333] Institut, University of Freiburg, D-7800 Edmund C. Burke, Department of Freiburg, Federal Republic of Germany Physiology, Louisiana State University [301] Medical Center, New Orleans, LA Läszlö Dezsi, Experimental Research 70112 [573] Department, Semmelweis University Claude Celotto, Institute of Medical School, Budapest, Hungary Biochemistry, University of Graz, [503] A-8010 Graz, Austria [245] Hans P. Dinges, Institute of Pathology, G. A. Charbon, Experimental University of Graz, Graz, Austria [43] Laboratory for Peripheral Circulation, University Hospital Utrecht, Utrecht, Heinrich Ditter, Department of Internal The Netherlands [495] Medicine, Justus-Liebig University, M. Cianciulli, Intensive Care D-6300 Giessen, Federal Republic of Department, II Faculty of Medicine, Germany [369] University of Naples, Napoli, Italy Marc Domb, Department of Intensive [271] Care, Erasme University Hospital, Free C. Oasen, Krankenhaus Itzehoe, 2210 University of Brüssels, Brüssels, Itzehoe, Federal Republic of Germany Belgium [393] [175] Hermann Esterbauer, Institute of C. G. Cochrane, Research Institute of Biochemistry, University of Graz, Scripps Clinic, San Diego, CA 92103 A-8010 Graz, Austria [245] [253] Erzsebet Feher, Department of Farag I. Coraim, Department of Anatomy, Semmelweis University Anaesthesiology and Intensive Care Medical School, Budapest, Hungary Medicine, The University of Vienna, [503] Vienna A-1090, Austria [611] R. Cuocolo, Intensive Care E. Fink, Abteilung für Klinische Department, II Faculty of Medicine, Chemie und Klinische Biochemie, University of Naples, Napoli, Italy Chirurgische Klinik Innenstadt der [271] Universität München, D-8000 München Ion V. Deaciuc, Department of 2, Federal Republic of Germany [159] Physiology, Louisiana State University Keith N. Frayn, MRC Trauma Unit, Medical Center, New Orleans, LA University of Manchester, Manchester 70112 [401] M13 9PT, United Kingdom [463] Contributors / xv H. Fritz, Abteilung für Klinische Wolfgang Hagmann, Biochemisches Chemie und Klinische Biochemie, Institut, University of Freiburg, D-7800 Chirurgische Klinik Innenstadt der Freiburg, Federal Republic of Germany Universität München, D-8000 München [301] 2, Federal Republic of Germany [127] Seth Hallström, Ludwig Boltzmann Günther Fuhrer, Department of Thoracic and Cardiovascular Surgery, Institute for Experimental University of Tübingen, D-7400 Traumatology, Vienna, Austria [591] Tübingen, Federal Republic of Germany Jänos Hamar, National Institute of [87,107] Traumatology, Semmelweis University Michael J. Gallimore, Department of Medical School, Budapest, Hungary Thoracic and Cardiovascular Surgery, [503] University of Tübingen, D-7400 Dale E. Hammerschmidt, Hematology Tübingen, Federal Republic of Germany Division, Department of Medicine, [87] University of Minnesota, Minneapolis, R. Geiger, Abteilung für Klinische MN 55455 [19] Chemie und Klinische Biochemie, Chirurgischen Klinik der Universität Peter Heckenast, Institute of München, D-8000 München 2, Federal Biochemistry, University of Graz, Republic of Germany [115] A-8010 Graz, Austria [245] Alfred Geißler, Institute for Mats Heideman, Department of Experimental Medicine, University of Surgery I, Sahlgren's Hospital, Cologne, D-5000 Cologne, Federal Göteborg, Sweden [3,11] Republic of Germany [95] Wolfgang Heller, Department of Anna Gergely, National Institute of Thoracic and Cardiovascular Surgery, Nutrition, Budapest, Hungary 1097 University of Tübingen, D-7400 [621] Tübingen, Federal Republic of Germany Anders Gidlöf, Clinical Research [87,107] Center, University Hospital, Linköping, David N. Herndon, Department of Sweden [63] Surgery, Shriners Burns Institute, E. Gono, Abteilung Arbeitsmedizin, Galveston, TX 77550 [539] Medizinische Einrichtungen der James G. Hilton, Department of Universität-Gesamthochschule Essen, Essen, Federal Republic of Germany Pharmacology, Shriners Burns Institute, [517] Galveston, TX 77550 [539] R. Jan. A. Goris, Department of D. B. Hinshaw, Research Institute of General Surgery, University Hospital St. Scripps Clinic, San Diego, CA 92103 Radboud, Nijmegen, The Netherlands [253] [55, 495] Susanne Hoberg, Department of A. B. Johan Groeneveld, Department Thoracic and Cardiovascular Surgery, of Internal Medicine, Medical Intensive University of Tübingen, D-7400 Care Unit, Free University Hospital, Tübingen, Federal Republic of Germany Amsterdam, The Netherlands [487] [107] xvi / Contributors H. Hoffmann, Abteilung für Klinische Theo Joka, Abteilung Unfallchirurgie, Chemie und Klunische Biochemie, Medizinische Einrichtungen der Chirurgische Klinik Innenstadt der Universität-Gesamthochschule Essen, Universität München, D-8000 München Essen, Federal Republic of Germany 2, Federal Republic of Germany [311,509,517] [115,127,159] Miklos Juhäsz, O. Korvin Hospital, Hans-Eberhard Hoffmeister, 1071 Budapest, Hungary [503] Department of Thoracic and Cardiovascular Surgery, University of Dietrich Keppler, Biochemisches Tübingen, D-7400 Tübingen, Federal Institut, University of Freiburg, D-7800 Republic of Germany [87,107] Freiburg, Federal Republic of Germany Pia Holmberg, Department of [301] Anesthesiology, Sahlgren's Hospital, J. Knöller, Institut für Medizinische, Göteborg, Sweden [11] Mikrobiologie und Immunologie, Geza Horpacsy, Institute for Bochum, Federal Republic of Germany Experimental Medicine, University of [311] Cologne, D-5000 Cologne, Federal Ernst Koller, Institute of Biochemistry, Republic of Germany [95] University of Graz, A-8010 Graz, Werner Hügel, Institute for Austria [245] Experimental Medicine, University of W. König, Institut für Medizinische, Cologne, D-5000 Cologne, Federal Mikrobiologie und Immunologie, Republic of Germany [95] Bochum, Federal Republic of Germany P. A. Hyslop, Research Institute of [311,317] Scripps Clinic, San Diego, CA 92103 K.-H. Konz, Medizinische Klinik, [253] Abteilung Kardiologie, University of Wilfried Dias, Second Surgical Tübingen, Tübingen, Federal Republic Department, The University of Vienna, of Germany [281] Vienna, Austria [611] Ernst Kreuzfelder, Medizinische Elizabeth Rogers Jacobs, University of Virologie und Immunologie, Arkansas for Medical Sciences, Little Universitätsklinikum Essen, Essen, Rock, AR 72205; present address: Federal Republic of Germany [509] Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612 [327] Peter Krösl, Ludwig Boltzmann Gary J. Jesmok, Department of Life Institute for Experimental Sciences, Travenol Laboratories, Inc., Traumatology, Vienna, Austria Round Lake, IL 60073 [333] [561,591] Marianne Jochum, Abteilung für Karel Kubat, Department of Pathology, Klinische Chemie und Biochemie, University Hospital St. Radboud, Chirurgischen Klinik Innenstadt der Nijmegen, The Netherlands [55] Universität München, D-8000 München Charles Lam, Sandoz 2, Federal Republic of Germany Forschungsinstitut, A-1235 Vienna, [121,175,509] Austria [427] Contributors / xvii Dagmar Langner, Department of Angela Menschik, Cardiovascular Experimental Surgery, Technical Research Laboratories, AB Hässle, University, 8000 Munich 80, Federal Mölndal, Sweden [63] Republic of Germany [419] Fred Mihm, Ludwig Boltzmann Günther Laufer, Second Surgical Institute for Experimental Department, The University of Vienna, Traumatology, Vienna, Austria [347] Vienna A-1090, Austria [611] K. M. Moser, University of California David H. Lewis, Clinical Research Medical Center, San Diego, CA 92103 Center, University Hospital, Linköping, [203] Sweden [63] Robert Moser, Institute of Rod A. Little, MRC Trauma Unit, Biochemistry, University of Graz, University of Manchester, Manchester A-8010 Graz, Austria [245] M13 9PT, United Kingdom [463] W. Mueller-Esterl, Abteüung für Joachim Lutz, Department of Klinische Chemie und Klinische Physiology, University of Würzburg, Biochemie, Chirurgische Klinik Würzburg, Federal Republic of Innenstadt, Universität München, 8000 Germany [503] München 2, Federal Republic of Pascal Luypaert, Department of Germany [175] Intensive Care, Erasme University Hugo Müller, Institute for Experimental Hospital, Free University of Brüssels, Medicine, University of Cologne, Brüssels, Belgium [393] D-5000 Cologne, Federal Republic of Asrar B. Malik, Department of Germany [95] Physiology, Albany Medical College of Froye Naess, Surgical Department, Union University, Albany, NY 12208 Ullevaal Hospital, University of Oslo, [33] Oslo, Norway [185] G. Martini, Institute of Anesthesiology Sandor Nagy, Institute of Experin^ntal and Intensive Therapy, University Surgery, University Medical Schoo, of Policlinico di Careggi, 50134 Florence, Szeged, Szeged, Hungary [599] Italy [259] Heinz Neuhof, Department of Internal F. Reinhard Matthias, Department of Medicine, Division of Clinical Internal Medicine, Justus-Liebig Pathophysiology and Experimental University, D-6300 Giessen, Federal Medicine, Justus Liebig University, Republic of Germany [369] 6300 Giessen, Federal Republic of Kathleen H. McDonough, Department Germany [289] of Physiology, Louisiana State G. P. Novelli, Institute of University Medical Center, Anesthesiology and Intensive Therapy, New Orleans, LA 70112 [573] University Policlinico di Careggi, 50134 Jesper Mehlsen, Department of Florence, Italy [259] Medical Physiology, Panum Institute Hans K.S. Nuytinck, Department of and Hvidovre Hospital, University of General Surgery, University Hospital Copenhagen, Copenhagen, Denmark St. Radboud, Nijmegen, The [629] Netherlands [55] xviii / Contributors Susanne Oberste-Beulmann, Hubert Reichte, Department of Unfallchirurgie, Universitätsklinikum Anaesthesiology, University of Munich, Essen, Essen, Federal Republic of 8000 Munich 70, Federal Republic of Germany [509] Germany [419] Udo Obertacke, Abteilung Bo Risberg, Department of Surgery I, Unfallchirurgie, Medizinische Sahlgrenska Hospital, Göteborg, Einrichtungen der Universität- Sweden [133] Gesamthochschule Essen, Essen, Federal Republic of Germany [509,517] Bryan L. Roth, Naval Medical Xavier J.M.W. Offermans, Research Institute, Bethesda, MD 20814 Department of General Surgery, [401] University Hospital St. Radboud, Elizabeth Roth, Department of Nijmegen, The Netherlands [55] Experimental Surgery, University of O. Ortolani, Intensive Care Medicine, Pees, Hungary 7643 [633] Department, II Faculty of Medicine, Peter Röttger, Department of University of Naples, Napoli, Italy Pathology, General Hospital, D-5160 [271] Düren, Federal Republic of Germany Eva Paul, Ludwig Boltzmann Institute [369] for Experimental Traumatology, Vienna, Tom E. Ruud, Surgical Department, Austria [165] Ullevaal Hospital, University of Oslo, Anton Philapitsch, Immuno 0407 Oslo 4, Norway Hämoderivate AG, A-1220 Wien, [185,193,211,227] Austria and Department of Thoracic and Kare Sander-Jensen, Department of Cardiovascular Surgery, University of Medical Physiology, Panum Institute Tübingen, D-7400 Tübingen, Federal and Hvidovre Hospital, University of Republic of Germany [107,141,159] Copenhagen, Copenhagen, Denmark Johan Pillgram-Larsen, Surgical [629] Department, Ullevaal Hospital, University of Oslo, 0407 Oslo 4, Anna Schiesser, Ludwig Boltzmann Norway [185,193,211,227] Institute for Experimental Ulrich Pison, Abteilung Traumatology, Vienna, Austria Unfallchirurgie, Medizinische [165,347] Einrichtungen der Universität- Günther Schlag, Ludwig Boltzmann Gesamthochschule Essen, Essen, Institute for Experimental Federal Republic of Germany Traumatology, Vienna, Austria [317,509,517] [xxv,43,165,347,561,591] Susan Pollak, Material Chemical K. P. Schmit-Neuerburg, Abteilung Works, Budapest, Hungary 1743 [633] Unfallchirurgie, Medizinische K.P. Heinz Redl, Ludwig Boltzmann Schmit-Neurburg, Abteilung Institute for Experimental Einrichtungen der Universität- Traumatology, Vienna, Austria Gesamthochschule, Essen, Federal [xxv,43,165,347,591] Republic of Germany [317] Contributors / xix Wolfgang Schönfeld, Institut Für Lani W. Smith, Department of Medizinische Mikrobiologie und Physiology, Louisiana State University Immunologie, Universität Bochum, Medical Center, New Orleans, LA Bochum, Federal Republic of Germany 70112 [573] [311,509] Lennart Smith, Department of Surgery I. U. Schraufstatter, Research Institute I, Sahlgrenska Hospital, Göteborg, of Scripps Clinic, San Diego, CA 92103 Sweden [133] [253] Hans-Peter Schuster, Medizinische R. M. Smith, University of California Klinik I, Städtisches Krankenhaus Medical Center, San Diego, CA 92103 Hildesheim, D-3200 Hildesheim, [203] Federal Republic of Germany [459] John J. Spitzer, Department of Eberhard Schütze, Sandoz Physiology, Louisiana State University Forschungsinstitut, A-1235 Vienna, Medical Center, New Orleans, LA Austria [427] 70112 [573] Werner Seeger, Department of Internal Judy A. Spitzer, Department of Medicine, Division of Clinical Physiology, Louisiana State University Pathophysiology and Experimental Medical Center, New Orleans, LA Medicine, Justus Liebig University, 70112 [401] 6300 Giessen, Federal Republic of R. G. Spragg, University of California Germany [289] Medical Center, San Diego, CA 92103 P. Sefrin, Institute of Anaesthesiology, [203,253] University of Würzburg, D-8700 Jan. O. Stadaas, Surgical Department, Würzburg, Federal Republic of Ullevaal Hospital, University of Oslo, Germany [477] 0407 Oslo 4, Norway William C. Shoemaker, Department of [185,193,211,227] Surgery, Los Angeles County King- Carsten Stadeager, Department of Drew Medical Center, University of Medical Physiology, Panum Institute California, Los Angeles, Los Angeles, and Hvidovre Hospital, University of CA 90059 [361] Copenhagen, Copenhagen, Denmark M. Siebeck, Chirurgische Klinik [629] Innenstadt, Universität München, D- 8000 München 2, Federal Republic of J. Sturm, Medzinische Hochschule Germany [115,121,127,141,159] Hannover, Hannover, Federal Republic John H. Siegel, Department of Surgery of Germany [311] Johns Hopkins University and Norbert Suttorp, Department of Department of Surgery, Maryland Internal Medicine, Division of Clinical Institute for Emergency Medical Pathophysiology and Experimental Services Systems, University of Medicine, Justus-Liebig University, Maryland, Baltimore, MD 21201 [439] 6300 Giessen, Federal Republic of Janet Simpson, Department of Life Germany [289] Sciences, Travenol Laboratories, Inc., Kornel Szabö, Burn Center, Central Round Lake, IL 60073 [333] Hospital, Budapest, Hungary 1553 [621] xx / Contributors R. Tani, Institute of Anesthesiology and Gregory M. Vercellotti, Hematology Intensive Therapy, University Division, Department of Medicine, Policlinico di Careggi, 50134 Florence, University of Minnesota, Minneapolis, Italy [259] MN 55455 [19] O. Thetter, Chirurgische Klinik Jean-Louis Vincent, Department of Innenstadt, Universität München, Intensive Care, Erasme University D-8000 München 2, Federal Republic Hospital, Free University of Brüssels, of Germany [121,127,159] Brüssels, Belgium [393] Lambertus G. Thijs, Department of Christa Vogl, Ludwig Boltzmann Internal Medicine, Medical Intensive Institute for Experimental Care Unit, Free University Hospital, Traumatology, Vienna, Austria Amsterdam, The Netherlands [487] [347,591] Martin Thurnher, Ludwig Boltzmann Reinhard Voss, Department of Internal Institute for Experimental Medicine, Justus-Liebig University, Traumatology, Vienna, Austria [347] D-6300 Giessen, Federal Republic of Germany [369] G. Tiegs, Physiologisch-Chemisches Institut, University of Tübingen, Hubert Walzl, Sandoz Tübingen, Federal Republic of Germany Forschungsinstitut, A-1235 Vienna, [281] Austria [427] Jorgen Warberg, Department of Gerd O. Till, Department of Pathology, Medical Physiology, Panum Institute University of Michigan Medical School, and Hvidovre Hospital, University of Ann Arbor, MI 48109 [235] Copenhagen, Copenhagen, Denmark Bela Török, Department of [629] Experimental Surgery, University of Peter A. Ward, Department of Medicine, Pees, Hungary 7643 [633] Pathology, University of Michigan Daniel L. Traber, Department of Medical School, Ann Arbor, MI 48109 Anesthesiology and Physiology, [235] University of Texas Medical Branch; H. F. Welter, Chirurgische Klinik and Department of Anesthesia Research, Innenstadt, Universität München, D- Shriners Burn Institute, Galveston, TX 8000 München 2, Federal Republic of 77550 [149,377,539] Germany [121,127,141] A. Trebbi, Intensive Care Department, A. Wendel, Physiologisch-Chemisches II Faculty of Medicine, University of Institut, University of Tübingen, Naples, Napoli, Italy [271] Tübingen, Federal Republic of Germany Elena R. Turco, Department of [281] Physiology, Louisiana State University Peter Wendt, Department of Medical Center, New Orleans, LA Experimental Surgery, Technical 70112 [401] University, 8000 Munich 80, Federal Philippe Van der Linden, Department Republic of Germany [419] of Intensive Care, Erasme University Stephen Westaby, Royal Postgraduate Hospital, Free University of Brüssels, Medical School, Hammersmith Brüssels, Belgium [393] Hospital, London, UK [75] Contributors / xxi H. Wiesinger, Pathologisches Institut, Gregor Wollenek, Second Surgical Universität München, D-8000 München Department, The University of Vienna, 2, Federal Republic of Germany [141] Vienna A-1090, Austria [611] Ernst Wolner, Second Surgical Claudia Willing, Ludwig Boltzmann Department, The University of Vienna, Institute for Experimental Vienna A-1090, Austria [611] Traumatology, Vienna, Austria [165] Gerda Zilow, Department of Frank J. Wilson, Jr., University of Immunologie, Universität Heidelberg, Oklahoma Health Sciences Center, Heidelberg, Federal Republic of Oklahoma City, OK 73104 [327] Germany [509]

Contents of Part B: Monitoring and Treatment of Shock 1. MONITORING OF SHOCK 1.1. Prognostic Indices and Scoring Scoring Systems and Predictors of ARDS and MOF / R. Jan A. Goris, Hans K.S. Nuytinck, and Heinz Redl The Use of Scoring Systems as Prognostic Parameter After Surgery and Trauma / Peter Lehmkuhl, M. Ludwig, and I. Pichlmayr Prediction of Outcome in Sepsis /H.B. Stoner Prognostic Indices in Septic Shock / Jesus Villar, Miguel A. Blazquez, Jose A. Bolanos, Juan J. Manzano, and Jose Quintana 1.2. Biochemical Parameters Quantification of Granulocyte Enzymes/Proteins With Immunoassays / H. Lang, S. Neumann, W. Rautenberg, H. Fritz, Marianne Jochum, and D. Inthorn Studies of Granulocyte Function (Chemiluminescence Response) in Postoperative Infection / Dietrich Inthorn, Thomas Szczeponik, Dieter Mühlbayer, Marianne Jochum, and Heinz Redl Elevated D-erythro-Neopterin Levels in Intensive Care Patients With Septic Complications / Wolfgang Strohmaier, Heinz Redl, Günther Schlag, and Dietrich Inthorn The Influence of Septic Shock on Plasma Proteins, Lymphocytes and Metabolie Parameters / Erich Roth, Rudolf Steininger, Ingrid Schindler, Gerhard Hamilton, Walter Mauritz, Friedrich Zekert, Manfred Mattausch, Eva Schönthal, Paul Sporn, and Josef Funovics Inhibition of Beta-FXIIa in Plasma of Volunteers and Polytraumatized Patients / Günther Fuhrer, Michael J. Gallimore, Wolfgang Heller, and Hans-Eberhard Hoffmeister Can the Outcome After Trauma of Sepsis be Predicted From Biochemical or Hormonal Parameters? / Thomas Pasch, Jörg Mahlstedt, Josef Pichl, Gernot Buheitel, and Edgar Pscheidl The Proenzyme Functional Inhibition Index as a Predictor in Septicemia / Ansgar O. Aasen 1.3. Hemodynamic Parameters Physiologie Monitoring and Therapy of High Risk Surgical Patients / William C. Shoemaker Hämodynamic Pattern in Septic Peritonitis / Heinz Köhler, W. Reichow, J. Martell, G. Köveker, and A. Schafmayer Early Metabolie and Vascular Tone Patterns in Lethal Sepsis / Ivo Giovannini, Giuseppe Boldrini, Carlo Chiarla, Marco Castagneto, and Giancarlo Castiglioni Judgement of Central Haemodynamics With and Without Swan Ganz Catheter in Septic Shock States / Gerhard Redl, Ernst Zadrobilek, Ingrid Schindler, Walter Mauritz, and Paul Sporn Hemodynamic Characterization of Sepsis / K. Lenz, A. Laggner, W. Druml, G. Graninger, G. Grimm, and B. Schneeweiß 1.4. Extra vascular Lung Water Intravascular Starling Forces and Extravascular Lung Water in Advanced Septic Shock States / Ernst Zadrobilek, Ingrid Schindler, Gerhard Redl, Walter Mauritz, Hermann Gilly, Paul Sporn, and Karl Steinbereithner Dynamics of Extravascular Lung Water in Major Burns / Anton N, Laggner, Kurt Lenz, Gernot Sommer, Wilfred Druml, Bruno Schneeweisz, Georg Grimm, and Gunter Kleinberger Extravascular Lung Water and Pulmonary Artery Pressure With Acute Respiratory Failure— Effect of Ketanserin Administration / W. Heinrichs, U. Fauth, and M. Halmägyi xxiii xxiv / Contents of Part B 2. TREATMENT OF SHOCK 2.1. Basic Supportive Therapy Prävention of ARDS and MOF by Prophylactic Mechanical Ventilation and Early Fracture Stabilisation / R.J.A. Göns Modern Strategies of Ventilatory Management in Shock / H. Benzer, M. Baum, J. Koller, W. Koller, G. Kroesen, and N. Mutz Therapeutic Approaches: Haemodynamic and Respiratory Complications in Septic Shock / P. Lawin, H.J. Lübbesmeyer, M. Möllmann, N. Mertes, and H. Van Aken 2.2. Volume Replacement Fluid Resuscitation in Canine Traumatic-Hemorrhagic Shock: Long-Term Comparison of Hydroxyethyl Staren vs. Ringer's Lactate / Uwe B. Brückner, Michael Albrecht, Lorenz Frey, and Lars-G. Hein Treatment of Experimental Mesenteric Shock by Different Fluids / Jänos Hamar, Joachim Lutz, Laszlö Dezsi, and Miklös Juhäsz Does Isovolemic Hemodilution Predispose to Infection? / Wolfgang Graninger, Franz X. Lackner, Reswan Khosropour, Christine Hlozanek, and Robert Kurz 2.3. Plasmapheresis and Hemofiltration Plasma Exchange in Septic Shock / Lars J. Bjertnaes Continuous Pump Driven Hemofiltration (CPDHF) in Septic Renal Failure / Paul Sporn, Walter Mauritz, Gerhard Redl, Ingrid Schindler, Karl Steinbereithner, and Ernst Zadrobilek Continuous Arterio-Venous Hemofiltration for the Treatment of Acute Renal Failure in Septic Shock / Wolfgang Reichow, Heinz Koehler, Klaus Dietrich, and Anton Schafmayer The Continuous Arterio-Venous Hemofiltration in Shock / H.C. Rau, K.H. Staubach, C. Hohlbach, and W. Klingler 2.4. Corticosteroids Corticosteroids in the Treatment of Septic Shock / William Schumer Effect of Methylprednisolone, Prednisolone and Dexamethasone on Granulocyte Function and Complement Activation / Heinz Redl, Herbert Lamche, Eva Paul, Anna Schiesser, and Günther Schlag Comparison of Different Corticosteroids in Rat Endotoxemia / Soheyl Bahrami, Anna Schiesser, Heinz Redl, and Günther Schlag Can Preoperative High Dose Corticosteroids Preserve Normal Pulmonary Permeability and Homeostasis? / Lennart Smith, Svenerik Andreasson, Tom Saldeen, and Bo Risberg 2.5 Specific Measures Influence of Parenteral Nutrition on Lung Surfactant in the Traumatized Rat / Soheyl Bahrami, Harald Gasser, Wolfgang Strohmaier, Heinz Redl, and Günther Schlag Effects of Surfactant Replacement on Respiratory Failure Induced by Free Oxygen Radicals / B. Lachmann, O.D. Saugstad, and W. Erdmann Glucose-Insulin-Potassium (GIK) in Hypodynamie Septic Shock / Walter Mauritz, Ingrid Schindler, Ernst Zadrobilek, and Paul Sporn Non-Adrenergic Inotropic Support in Septic Shock / Marc Domb, Corinne De Boelpaepe, and Jean-Louis Vincent Effects of Endotoxin and Gadolinium Chloride on Acute Septic Peritonitis and Septic Shock in Rats / George Lazar, Jr., Elizabeth Husztik, and George Lazar First Vienna Shock Forum, Part A: Pathophysiological Role of Mediators and Mediator Inhibitors in Shock, pages 121-125 © 1987 Alan R. Liss, Inc.

INFLÜENCE OF THE LYSOSOMAL ELASTASE INHIBITOR EGLIN ON THE DEVELOPMENT OF INTERSTITIAL LUNG EDEMA IN E.COLI BACTEREMIA IN PIGS

H.F. Welter, M. Siebeck, 0. Thetter, M. Jochum

Chirurgische Klinik Innenstadt und Chirurgische Poli• klinik der Universität München, Abteilung für Klinische Chemie und Klinische Biochemie in der Chirurgischen Klinik der Universität München

INTRODUCTION

The importance of unspecific proteolysis in inflamma- tory disease processes is currently gaining common inte- rest. An imbalance between the endogenous inhibitor/ Protease ratio in favour of the proteases might be the reason for extensive proteolysis of tissue structures and humoral factors. Eglin c, an 8100 Da miniprotein from the medical leech, is a potent inhibitor of the lysosomal proteinases elastase and cathepsin G. Its resistance against oxidation and proteolysis (Seemüller et al. 1981) suggested its use for an antiproteolytic therapy. The production of sufficient amounts of eglin c (r-eglin c) by recombinant DNA technology (Rink et al. 1984) made such studies possible. We wanted to examine whether eglin medi- cation could be of potential benefit during a complex inflammatory Situation such as an experimentally induced E.coli septicemia with respiratory failure in pigs.

MATERIALS AND METHODS

Weaned domestic pigs (body weight around 20 kg) spon- taneously respirating under pentobarbital anesthesia were used. Catheters were placed to monitor blood pressures, cardiac Output and extravascular lung water (EVLW, double indicator method, Lewis et al. 1979) and to collect blood and samples. All pigs (n = 14) were given an in- 122 / Weiteretal fusion of 3 x 10 live cells obtained from freshly cultured E.coli (ATCC 20399), in 24 ml saline over a period of 2 hrs. In addition, 7 animals were given 200 ml 0.9% saline (group 1) and 7 animals r-eglin c in a dosis of 3.85 mg / kg x h in 200 ml 0.9% saline (group 2), each for 4 hrs. All intravenous infusions were started simulta- neously, 60 min after the end of the Operation. r-Eglin c concentration in plasma and urine samples was determined by radial immunodiffusion. Alpha-2-macroglobulin (alpha-2- M) and antithrombin III (AT III) levels were estimated by chromogenic Substrate assays (Boehringer, Mannheim), factor XIII (F XIII) by a coagulation method (Behring- werke, Marburg). Observation was terminated at death or after 30 hrs and lung tissue was fixed immediately. Severity of lung tissue damage was assessed in hematoxy- line-eosine stained sections and graded into severe, moderate, or absent interstitial edema. For comparison of lung damage, the Mantel-Haenszel test was used. Unpaired data were compared with the two-tailed t-test.

RESULTS

Antithrombin III and Factor XIII. Significant con- sumption of these proteins was observed in the bacteremia group 1 but was clearly reduced by administration of r- eglin c (group 2). The mean of the last measured AT III level was 80.9 + 12.8% in group 1 vs. 97.4 + 10% in group 2 (p < 0.02). The mean of the last measured FX III level was 53.9 + 15.7% in group 1 and 76.3 + 13.2% in group 2 (p < 0.015). Light microscopical evaluation of long tissue. Severe interstitial edema (3 cases) or moderate interstitial edema (4 cases) and accumulation of nucleated cells was noted in all tissue sections of group 1 animals. Other typical features were not constant, e.g. peribronchial, perivascular and alveolar edema, atelectasis and intravas- cular clot formation. In group 2, moderate edema was found in 2 animals and 5 animals showed no sign of increased vascular permeability. The difference was significant (Fisher's exact p < 0.01). Plasma levels and urinary excretion of eglin. Maximum levels of r-eglin c in plasma were attained after 4 hrs and ranged from 1.9 to 5.1 umol/1. Plasma levels remained high in animals with impaired renal elimination. In ani• mals with normal renal function, maximum plasma levels R-Eglin C and E. coli Septicemia in Pigs / 123 ranged from 2.9 to 3.7 umol/1 and eglin was not detectable any more after 6 to 12 hrs. In these animals, 75 up to 95% of the total administered eglin doses were found in the urine within 12 hrs. Mortality. In group 1, 3 out of 7 animals survived the Observation period, 4 died after 3.5, 6.7, 6.8, and 8.4 hrs, respectively. In group 2, 4 out of 7 animals survived the 30 hrs Observation period, 3 died after 15.1, 15.3 and 18.4 hrs, respectively. Mean arterial blood pressure (AP). In all animals, AP dropped initially by 20 to 30 mm Hg. However, after the first 2 to 3 hrs AP recovered in group 2 animals and declined further until death in group 1 animals (n.s.). Extravascular lung water« In group 1, EVLW rose steeply from 16 + 4.2 ml/kg at zero hrs to 24 + 10 ml/kg at 7 hrs whereas it increased only slightly during this time interval in group 2 from 13 + 1.8 ml/kg to 17 + 3.7 ml/kg (n.s.). Alpha-2-macroglobulin. alpha-2-M decreased signifi- cantly in all experiments indicating activation of proteo• lysis. However, consumption of alpha-2-M was considerably less severe in group 2 animals. Other parameters. The following measurements dis- played a typical response of the animals to septicemia: White blood cells showed a deep initial leucocytopenia followed by leucocytosis. Platelet counts dropped to 11% up to 50% of the starting values. Arterial blood gas analyses showed hypoxemia, acidosis and hypocapnia. The pulmonary circulation reacted with an enormous pulmonary arterial hypertension and decreased cardiac Output. All these parameters were not substantially influenced by eglin administration. Urine Output decreased and was better maintained in group 2 than in group 1 animals.

DISCUSSION The light microscopical observations and the measure• ments of EVLW clearly indicate that the accumulation of interstitial fluid can be prevented by r-eglin c treat• ment. This favours the assumption that at least elastase from polymorphonuclear granulocytes (PMN) is involved in the pathophysiology of lung tissue damage during septic• emia (Lee et al. 1981). AT III and F XIII plasma levels were better maintained under eglin treatment. We prefer to interpret this finding as an indication of an effectively 124 / Welter et al

inhibited unspecific proteolysis (Fritz et al. 1984) rather than an inhibition of coagulation. In humans and in dogs, fatal septicemia was also associated with an exten• sive systemic proteolysis as assesssed by F XIII and AT III activity in plasma (Jochum et al. 1981, Jochum et al. 1984). Correspondingly, protection of these proteins from proteolysis as tried in this study apparently im- proves prognosis. Alpha-2-M, a potent inhibitor of various lysosomal and other proteinases, is also a highly suscep- tible Substrate for both PMN elastase and PMN cathepsin G. The observed difference between the groups in the plasma levels of alpha-2-M may be explained therefore by a re- duced consumption of this inhibitor due to the protective effect of eglin c. Remarkably, eglin c levels in plasma between 2 and 5 umol/1 seem to be sufficient to inhibit the liberated lysosomal proteinases substantially. The actual eglin c level is, however, strongly influenced by the kidney function because elimination of this inhibitor occurs chiefly by renal excretion.

SUMMARY

Infusion of 3 x 1010 live E.coli cells into anesthe- tized piglets induced severe septicemia with characteris- tic alterations in systemic and pulmonary circulation, lung function and morphology, blood cell counts and plasma protein composition. The simultaneous infusion of the elastase-cathepsin G inhibitor, r-eglin c, in a dosis of 3.85 mg / kg x h for 4 hrs, reduced mortality, plasma protein consumption, and accumulation of interstitial fluid in the lungs. These findings are in favour of the concept that during septicemia the balance between libe• rated lysosomal proteinases and their extracellular inhi- bitors is severely disturbed. It can be at least partially restored by administration of an exogenous elastase inhi• bitor.

ACKNOWLEDGEMENTS

This work was financed in part by the Deutsche Forschungsgemeinschaft (WE-1002/2-1). The authors wish to thank Prof. Dr. H. Fritz for valuable discussions, Prof. Dr. L. Schweiberer for generous support, Dr. H. Wiesinger for light microscopy of lungs, M. Gogl, R. Hell, S. Lenk, R-Eglin C and E. coli Septicemia in Pigs / 125 M. Meier and E. Schaller for excellent technical assis- tance, U. Elster, M. v. Kramolin and P. Schombert for valuable help and Plantorgan-Werk and Ciba-Geigy for pro- viding us with r-Eglin c.

REFERENCES

Jochum M, Witte J, Schiessler H, Selbmann KH, Ruckdeschl G, Fritz H (1981). Clotting and other plasma factors in experimental endotoxemia: Inhibition of degradation by exogenous Proteinase inhibitors. Eur Surg Res 13: 152-168. Jochum M, Duswald H, Neumann S, Witte J, Fritz H (1984). Proteinases and their inhibitors in septicemia - basic concepts and clinical implications. In Hörl WH, Heidland A (eds): "Proteases", Plenum, pp 391-404. Fritz H, Jochum M, Duswald KH, Dittmer H, Kortmann H (1984). Granulocyte proteinases as mediators of unspecific proteolysis in inflammation: a review. In Goldberg DM, Werner M (eds): "Selected Topics in Clinical Enzymology, Vol. 2", Berlin: W. de Gruyter, pp 305-328. Lee CT, Fein AM, Lippman M, Holtzman H, Kimbel P, Weinbaum G (1981). Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory distress Syndrome. N Engl J Med 304: 192-196. Lewis FR, Elings VB, Sturm JA (1979). Bedside measurement of lung water. J Surg Res 27: 250-261. Rink H, Liersch M, Sieber P, Meyer F (1984). A large fragment approach to DNA synthesis: total synthesis of a gene for the protease inhibitor eglin c from the leech Hirudo medicinalis and its expression in E.coli. Nucl Acids Res 12: 6369-6387. Seemüller U, Fritz H, Eulitz M (1981). Eglin: Elastase- cathepsin G inhibitor from leeches. Methods Enzymol 80: 804-816. Index A23187 calcium ionophore, 290, 314, 315 heart Stimulation, 599-600, 603-607 Acidosis, cardiodepressant, 600 Antihistamines, multitherapy regimen for en• ADP-iron, cytotoxic lipid peroxidation prod- dotoxemia, pigs, 212, 213, 222, 228 ucts, rat liver microsomes, 247-249 Antioxidant drugs in shock therapy, 271-279 Adrenal gland, catecholamines, multiple ascorbic acid, 276 trauma, and ARDS, 479 BHT, 276 Adrenaline. See Epinephrine vs. granulocyte aggregation, 276-277 arAdrenergic receptors, transmembrane sig- iron role, 272 naling perturbation, endotoxemia, rat lipid peroxidation, 274-275 hepatocyte, 406-407, 415 vs. malondialdehyde formation, 276, 278 0-Adrenergic Stimulation, myocardial dys- a-MPG, 276 function in sepsis, 576-577 natural Systems, 272 isoproterenol, 577, 578 loss in shock, 273-275 Albumin flux, microvascular permeability, propyl-gallate, 276 septic shock, 490-491 a-tocopherol, 276 Aldehydes, lipid peroxidation products, rat see also Oxygen free radical scavengers, liver microsomes, 245-249; see also Prophylaxis and treatment of ex• Malondialdehyde (MDA) perimental shock, rat Alveolar cell reactions, posttraumatic lung Antioxidant protection vs. free radical me- failure and ARDS, 509-514 diated myocardial injury, dogs, AaD02, 510 633-639 bronchoalveolar lavage, 509-513 ECG, 635 chemiluminescence of neutrophils, 510, GSH, 635-639 511 ischemia-repertusion, 634-639 complement, 510, 512 lipid peroxidation, 633-635, 638-639 elastase, 510-513 MDA, 635-636 cf. vascular proteins, 513 MTDQ-DA, 633, 636, 639 extravascular lung water, 510-512 SOD, 635-639 leukotrienes, 510-512 Antiplasmin Polytrauma score, 510 multitherapyregimen for endotoxemia, see also Bronchoalveolar lavage pigs, 216, 219 Alveolar cells, type II, 103 ot2-y very high dosage aprotinin in Poly• Alveolar hypoxia, arachidonic acid System trauma, 177, 180 activation, isolated lung, 294-295 Antiproteases. See Protease inhibitors in en• a-Amanitin, 302, 306, 307 dotoxemia; specific inhibitors Amylase, aprotinin and Cl esterase inhibitor Antithrombin III, 40 infusion and pancreatic shock, pig, Cl-esterase inhibitor 195 early E. coli septicemia, pigs, 142, Anaphylatoxins (C3a and C5a). See under 144 Complement activation and elastase release, extracorporeal Angiotensin II, 382, 402 circulation, 108, 111

641 642 / Index eglin, elastase inhibitor, and lung edema, Aprotinin, very high dosage, Polytrauma, septic pigs, 122-124 175-182 kallikrein-kinin System activation, lung, a2-antiplasmin, rocket immunoelectro- E. coli septic sheep, 134, 136-138 phoresis, 177, 180 multitherapy regimen for endotoxemia, feasibility study, 176 pigs, 212, 213, 216, 217, 220, 221, infusion, 176-178, 181 228 kallikrein inhibition, 175-181 ai-Antitrypsin, Cl-esterase inhibitor, early lung function, 180, 182 E. coli septicemia, pigs, 144 plasma levels, 178-181 Aortic endothelium, oxidant injury, cultured plasmin inhibition, 179 cells, 254-255 renal function, 180-182 Aorto-coronary bypass. See Cardio-pulmo- Creatinine, 181 nary bypass urine Output, 180-181 Apnoe, extracorporeal circulation, biochemi• tolerance, 182 cal lung monitoring during CPB, 96, Aptoglobin, 272 98-100, 103-104 Arachidonic acid, 170, 260, 302, 305-307 Apple H, 568 ibuprofen and ETX-stimulated inflamma- Aprotinin tion, 334, 342, 344 and kallikrein lipid peroxidation products, cytotoxic, rat activation, and Cl-esterase inhibitor, liver microsomes, 235, 247 159-163 see also Eicosanoids; Prostaglandin en- activation during CPB, 87-89, 91, 93 tries; Thromboxanes infused, kinin-induced pathology in Arachidonic acid System activation, isolated ARDS development, pig, rabbit lung, 289-298 alveolar hypoxia, 294-295 127-130 bacterial toxins, 295-296 MDF release during CPB, 611-615, complement, 292-293, 295 617-618 granulocytes, 292, 296-298 multitherapy regimen for endotoxemia, elastase, 296 pigs, 212, 218, 220, 228 oxygen radicals, 296 Aprotinin and Cl-esterase inhibitor infusion and hemodynamics, pulmonary, 289-298 and pancreatic shock, pig 193-200 PAP, 292-295 amylase, 195 kallikrein-kinin System, 289, 291, 292 hemodynamics, improved, 193 leukotrienes, 291, 293, 296 arterial pressure, 193, 195 Prostaglandins, 289, 291, 294-296 cardiac Output, 194-195 thromboxanes, 291, 293-297 kallikrein, 194, 196-200 ARDS (adult respiratory distress Syndrome) inhibition, 193-197, 199 and complement in shock, 4, 6 kinin, 199 development, kinin-induced pathology, kininogen, 199 kallikrein infusion, pig, 127-130 prekallikrein, 194, 196, 199, 200 elastase and leukocyte counts, septic pig survival rate, 193 lung, 115, 118 Aprotinin, ceilular effects, 165-171 granulocyte mediation of tissue injury, granulocyte function, 165-168, 170-171 23-24 elastase release, 166-169 pulmonary membranes, 75, 76, 78, phagocytosis, 169, 171 83-84 platelets, 165, 170, 171 leukostasis, quantitative estimation, 50 Superoxide radical, 165, 166, 169 limb ischemia, C3a and C5a as mediators SOD, 166 of inflammation, 11 Index / 643 microvascular permeability, septic shock, infusion and pancreatic shock, pig, 487 193, 195 MOF, wound inflammatory mediators plasma kallikrein-kinin System activa• and, 534 tion, 160-161 oxidant injury, cultured cells, 253 eglin, elastase inhibitor, and lung edema, physiologic-metabolic correlations, septic septic pigs, 123 shock, 441, 446 ETX shock (£. coli), dog model, 394, a, -proteinase inhibitor bioavailability, in- 395, 398 jected vs. aerosolized, 203-204 multitherapy regimen for endotoxemia, whole body inflammation, trauma patient hemodynamics, 229-230 autopsy study, 55-60 oxygen and blood flow, regional differ• see also Alveolar cell reactions, posttrau- ences in early sepsis, 501 matic lung failure and ARDS; Cat- trypsin-induced shock, hemodynamics echolamines, multiple trauma, and and proteolysis, 189-191 ARDS; Leukotrienes and lipid me• Body temperature diators in ARDS pathogenesis; BW755C in endotoxemia, 355, 357, 355, Phospholipid lung profile, ARDS 357 in Polytrauma patients; Prostaglan• ibuprofen and ETX-stimulated inflamma• din Ei administration in ARDS, tion, 340, 341 septic and post-surgery patients Bradykinin, 93, 185, 190, 192, 289, 292 Aryl sulfatase, 379 ETX, cause of mediator release in sepsis, Ascorbic acid, 276 380, 385, 387, 388 ATP, oxidant injury, cultured cells, 254 kallikrein-kinin System activation, lung, Atrium, left, extracorporeal circulation, bio• E. coli septic sheep, 137-138 chemical lung monitoring during multitherapy regimen for endotoxemia, CPB, 96-98, 101, 102, 104 pigs, 220-221 Atropine and heart rate in hypotensive cen• Branched chain amino acids tral hypovolemia, 629-631 cardiovascular abnormalities, septic Autopsy, leukostasis estimation, posttrau- shock, 449, 451,454-456 matic lung, 45-49 leucine as heart depressant factor, 601 diagnoses, 46-47 Bronchoalveolar lavage see also under Inflammation, whole body alveolar cell reactions, posttraumatic lung failure and ARDS, 509-513 Bacterial toxins, arachidonic acid System ac• elastase-apPI complex and leukocyte tivation, isolated lung, 295-296 counts, septic pig lung, 116-117, Bacteroides fragilis, 447 115 B cells,5, 380 leukotriene generation, Polytrauma pa• BHT, 276 tients with ARDS, 312-314 Bilirubin, 11, 13-15, 17 and phospholipid lung profile, ARDS, Bioavailability. See al-Proteinase inhibitor 518, 520 bioavailability, injected vs. a \ rproteinase inhibitor bioavailability, in• aerosolized jected vs. aerosolized, 203-205 Blood. See Coagulation; Oxygen and blood Bronchoscopy, 205 flow, regional differences, early sep- Burns sis; Oxygen free radicals, LPS gener- MOF, wound inflammatory mediators ation, fresh human blood and, 525, 526, 528, 532 Blood pressure infected cf. uninfected, 527 aprotinin and Cl esterase inhibitor nickel 644 / Index and heart depressant factors, 600 homeostasis, altered, myocardial dysfunc• myocardial damage, 622 tion in sepsis, 579, 581, 583, 584, Burn shock and resuscitation, 539-552 587 compliance, pulmonary, 550 transmembrane signaling perturbation, dog, 541, 550 endotoxemia, rat hepatocyte, extravascular lung water, 548-550 401-405, 409-410, 413-416 fluid resuscitation, 543, 544, 552 IP3-stimulated release, 413-415 hemodynamics, 540-543 Camera, gamma,microvascular permeability, human, 542, 543, 551 septic shock, 487, 491 inhalation injury, 544-552 Capillaries. See Microvascular permeability, C02, 546, 547, 551 endotoxemia/septic shock intubation, 551-552 Carbohydrate oxidation, flow or catabolic Surfactant, 550-551 phase, 465, 466 Ventilation, 551 Carbon monoxide, inhalation injury, burn lymph, 549-550 shock and resuscitation, 546, 547, 551 microvascular permeability, 539-541, 549 Cardiac Output mortality, 544, 545 aprotinin and Cl esterase inhibitor infu• plasma volume, 540-542 sion and pancreatic shock, pig, PMNs, 539-540, 547-549 194-195 pulmonary dysfunction, 544, 546 ETX edema, 548-550, 552 cause of mediator release in sepsis, sheep, 548, 551 377, 381,382, 385, 387, 388 shock (E. coli), dog model, 393-394, thromboxanes, 541, 548 396-398 Verapamil, 542 ibuprofen andETX-stimulated inflamma• Butylated hydroxytoluene, 276 tion, 338, 340 BW755C (NSAID) effect on endotoxemia, multitherapy regimen for endotoxemia, 302, 347-358 hemodynamics, 216-218, 229, 233 body temperature, 355, 357 myocardial dysfunction in sepsis, 575, cf. corticosteroids, 356-357 579, 584 hemodynamics, 356-357 oxygen and blood flow, regional differ- leukocytes, 347-350, 352, 353, 357 ences in early sepsis,496, 498 lipooxygenase and cyclooxygenase inhibi• PGE, administration in ARDS, 361 tion, 302, 347, 358 physiologic-metabolic correlations, septic lymph flow, 347, 349, 353-355, 357 shock, 440-442 microvascular permeability, 348, 354, trypsin-induced shock, hemodynamics 357 and proteolysis, 189-191 platelets, 348, 351 see also Heart entries rats, 347-352, 357 Cardiopulmonary bypass. See Kallikrein- mortality, 349, 350 kinin System activationduring aorto- sheep, 347-349, 353-357 coronary bypass (CPB); under Extra- MPAP, 353, 357 corporeal circulation; Granulocytes, thromboxane, 347, 350, 352, 355-357 mediation of pulmonary membrane damage; Myocardial depressant factor Calcium Cardiovascular abnormalities, metabolic ba- binding, inotropic plasma substances, sis, 446-453, 455-456; see also LMW, prolonged shock, 596 Hemodynamics Channel blockers, burn shock and resusci• Catabolic phase, metabolic changes in injury, tation, 542; see also Verapamil 463, 465-469 Index / 645 cf. starvation, 465-466 antithrombin III, 142, 144 Catalase, oxygen free radicals and lung in• «i-antitrypsin, 144 jury, 238, 240, 272, 274 factor XDJ, 142, 144 Catecholamines leukocyte count, 143, 145 heart Stimulation, 599-600, 603-607 lung edema, 144 injury cf. sepsis, 469, 470 a2-macrogiobulin, 142, 143, 145 see also Epinephrine (adrenaline) platelets, 144 Catecholamines, multiple trauma, and prokallikrein, 142, 143, 145 ARDS, 477-481,483-486 Chemiluminescence activation of neutrophils, alveolar cell reactions, post- complement, 477, 478 traumatic lung failure and ARDS, kallikrein-kinin System, 477 510-511 activation of coagulation system, 477, oxygen free radicals, LPS generation, 479-481 blood, 420-422 fibrin, 480-481 lucigenin, 420, 422, 425 fibrinogen, 480-481 luminol, 420-424 thrombin, 479, 480, 485-486 epinephrine, 478, 483-486 Superoxide radical, 422 erythrocytes,479 Chemotaxis and thrombin, lung microvascu• norepinephrine, 478, 483-486 lar injury, 33 pituitary and adrenal glands, 479 Chromatography, HPLC trauma scores, 478, 480, 484 leukotriene generation, Polytrauma pa• Cathepsin G, 124 tients with ARDS, 312-313 Ceruloplasmin, 272 lipid peroxidation products, cytotoxic, rat Cl-esterase inhibitor, 191 liver microsomes, 246-247 and aprotinin, plasma kallikrein-kinin and phospholipid lung profile, ARDS, system activation, 159-163 517-521 and complement in shock, 4 reverse phase, inotropic LMW plasma and endotoxemia, 153 substances, prolonged shock, 594 multitherapy regimen, pigs, 212, 213, Chromogenic Substrates, 185, 186, 191, 220, 221, 228 213-215 kallikrein system activation during CPB, Chronotropic effects, myocardial dysfunction 89, 92, 93 in sepsis, 576-578 see also Aprotinin and Cl-esterase inhibi• Cirrhosis, 365 tor infusion and pancreatic shock, Clinical trial, PGEj administration in ARDS, Pig 361-366 Cl-esterase inhibitor and elastase release, ex- Coagulation tracorporeal circulation, 107-113 activation, catecholamines, multiple antithrombin III, 108, 111 trauma, and ARDS, 477, 479-481, complement system inhibitor, 107 485-486 elastase-ai-proteinase inhibitor complex, DIC, 59 107, 112, 113 MOF, 460, 462 0-factor XHa, 108, 110 Protease inhibitors in endotoxemia, heparin, 108 153-154 kallikrein-kinin system inhibitor, see also specific factors and system 107-110, 113 Cobra venom, 236-240, 380 prekallikrein, 107-109, 113 Colony stimulating factor, granulocyte- Cl-esterase inhibitor, early E. coli septi• monocyte, 432-433 cemia, pigs, 141-146 Complement activation, 3-7 646 / Index alveolar cell reactions, posttraumatic lung Cyclooxygenase inhibition failure and ARDS, 510, 512 BW755C in endotoxemia, 302, 327, 358 arachidonic acid system activation, iso- ibuprofen, 327-328 lated lung, 292-293, 295 and ETX-stimulated inflammation, B cell function, 5 334, 344 C3a, 3-6, 77, 78, 85, 510, 512 prostacyclin in ETX shock, 369-370 C3b opsonization, 15, 20 Cysteinyl leukotrienes, 301, 303-307, 323 C5a, 3-6,20, 22-23, 77, 80, 81, 235, hepatobiliary elimination inhibited by 237, 238, 274 ETX, 304, 305, 307 C5-derived chemotactic activity, 236-238 catecholamines, multiple trauma, and Degranulation, leukostasis, quantitative esti- ARDS, 477, 478 mation, 48-49 Cl esterase inhibitor, 4 Dextran sulfate, 160-163 ETX, cause of mediator release in sepsis, Dialysis-associated neutropenia, 21 379 Diarrhea, ETX shock (£. coli), dog model, granulocyte mediation of tissue injury, 394, 396 20-24 Disseminated intravascular coagulation, 59 during CPB, 77-78, 84 DNA, Single Strand breaks, oxidant injury to inhibition, Cl-esterase inhibitor and elas• tase release, extracorporeal circu- cultured cells, 256-257 lation, 107 Dog model, E. coli endotoxin shock, macrophages, 5 393-398 methylmethacrylate cement in hip sur• gery, 6 Ebselen (selenium Compound), protection vs. MOF, 3, 4, 7 endotoxin shock ingalactosamine-sen- ARDS, 4, 6 sitized rodents, 281-287 oxygen free radicals and lung injury, eicosanoid metabolism interactions, dia• 235-238 gram, 287 whole body inflammation, trauma patient glutathione peroxidase, 282, 285, 286 autopsy study, 59-60 hemodynamics, 282, 283 see also under Ischemia hepatitis, 281,284, 285 Computers, 568 leukotrienes, 281, 284-286 Apple II, 568 liver, 283, 284, 286 Software, LAMS, 335, 337 ECG Contractility, 321-322, 567, 569, 574, 576, antioxidant protection vs. free radical me- 579, 581, 584 diated myocardial injury, 635 Corticosteroids cf. BW755C in endotoxemia, Ni release, myocardial damage, 621-623, 356-357; see also specific Steroids 625 Cortisol, 467, 470 Eglin, elastase inhibitor, influenae on lung CPAP, burn shock and resuscitation, 551 edema, septic pigs, 121-124 Creatinine antithrombin III, 122-124 aprotinin, very high dosage, Polytrauma, blood pressure, 123 181 E. coli, 121-122 limb ischemia, C3a and C5a as mediators extravascular lung water, 123 of inflammation, 13-15, 17 factor Xffl, 122-124 CSF, granulocyte-monocyte, 432-433 a2-macroglobulin, 122-124 Cyclic AMP and cyclic GMP, transmem- plasma levelsand urinary excretion, brane signaling perturbation, endotox• 122-123 emia, rat hepatocyte, 402, 403 Eicosanoids Index / 647 ibuprofen and ETX-stimulated inflamma• and platelets, 26 tion, 334, 342, 344 neutrophil adherence to, fibrin-neutrophil metabolism, ebselen protection vs. ETX interactions, lung microvascular shock in galactosamine-sensitized injury, 40 rodents, 287 oxygen free radicals and lung injury, 236, see also Arachidonic acid entries; specific 238 eicosanoids Endotoxemia. See also BW755C Elastase, granulocyte (NSAID)effect on endotoxemia; Pro• alveolar cell reactions, posttraumatic lung tease inhibitors in endotoxemia; Mi• failure and ARDS, 510-513 crovascular permeability, aprotinin, cellular effects, 166-169 endotoxemia/septic shock; Transmem• arachidonic acid system activation, iso- brane signaling perturbation, endotox• lated lung, 296 emia, rate hepatocyte extracorporeal circulation, biochemical Endotoxemia, multitherapy regimen, pigs, lung monitoring during CPB, 96, 211-222, 227-233 97, 100-104 antihistamine (Promethazin), 212, 213, leukostasis, quantitative estimation, 50 222, 228 Proteinase inhibitor bioavailability, in- antiplasmin, 216, 219 jected vs. aerosolized, 203, 207 gentamicin, 222 release during CPB, mediator of pulmo• hemodynamics, 216-221, 227-233 nary membrane damage, 82-83 arterial blood pressure, 229-230 see also Cl-esterase inhibitor and elastase cardiac Output, 216-218, 229, 233 release, extracorporeal circulation; left ventricular stroke work, 230, 231, Eglin, elastase inhibitor, influence 233 on lung edema, septic pigs mean pulmonary artery pressure, 230 Elastase-ofj-proteinase inhibitor complex, oxygen tension/saturation, 232, 233 PCWP, 232 and leukocyte counts, septic pig lung, pulmonary vascular resistance, 218, 115-118 220, 230, 231 ARDS, 115, 118 Swan-Ganz catheter, 228 bronchial washings, 116-117 systemic vascular resistance, 216, bronchoalveolar lavage, 115 218, 219, 230 E. coli, 116-118 kallikrein-kinin system activation, 212- ELISA, 115-116 215,220, 221,227 Electron microscopy, Ni release and myocar• bradykinin, 220-221 dial damage, 622, 625 ketanserin, 212, 213, 222, 228 Electron spin, PBN, oxygen radical scaven- methylprednisolone, 212, 213, 220-222, gers, 261,262, 267, 268 228 resonance, 261, 262, 267, 268 naloxone, 212, 213, 227, 228 trapping, 261-268 plasma endotoxin, chromogenic Substrate ELISA, 115-116, 127, 130 measurement, 213-215 Endorphins, 212, 227 Protease inhibitors /3-, 385, 389 antithrombin III, 212, 213, 216, 217, Endothelium/endothelial cells 220,221,228 aortic, oxidant injury, cultured cells, aprotinin, 212, 213, 220, 228 254-255 Cl-esterase inhibitor, 212-213, 220, damage after endotoxin activation, granu• 221, 228 locyte mediation of tissue injury, Endotoxemia, thromboxane synthetase inhib• 25-28 itors, 328-329 648 / Index Endotoxin (ETX) cardiac Output, 393-398 endothelial damage, granulocyte media- diarrhea, 394, 396 tion of tissue injury, 25-28 fluid infusion, 394, 395, 398 and platelets, 26 heart rate, 394, 395 leukotrienes as mediators of shock and lactate, 394, 3%, 397 tissue trauma, rat, 311-316 vascular resistance, systemic, 3%, MOF, wound inflammatory mediators 397 and, 527-532, 534 ibuprofen, increased survival, 327-330 myocardial dysfunction in sepsis, 576, see also Prostacyclin, intravenous, in 584 endotoxin shock, rabbit; Septic cell membrane effect, 576 shock entries oxygen radical scavengers, Prophylaxis Epinephrine (adrenaline), 467, 472, 473 and treatment, 262-264 catecholamines, multiple trauma, and receptor competition,lipid X inhibition of ARDS, 478, 483-486 LPS neutrophil activation, 434 transmembrane signaling perturbation, Salmonella abortus equi, 282 endotoxemia, rat hepatocyte, see also Ebselen (selenium Compound), 409-412 protection vs. endotoxin shock in Erythrocytes, catecholamines, multiple galactosamine-sensitized rodents; trauma, and ARDS, 479 Ibuprofen effect on ETX-stimula- Escherichia coli, 328, 402, 404, 420, 423, ted inflammation 447 Endotoxin, cause of mediator release in sep• sis, overview, 377-389 eglin, elastase inhibitor, and lungedema, B cells, 380 septic pigs, 121-122 bolus cf. infusion of pulses, 381-384, elastase and leukocyte counts, septic pig 386, 388 lung, 116-118 bradykinin, 380, 385, 387, 388 ETX shock, dog model, 393-398 cardiac Output, 377, 381-382, 385, 387, MOF, ETX and, 528-529, 531 388 see also Cl-esterase inhibitor, early E. leukotrienes, rat, 311-316 coli septicemia, pigs; Kallikrein- lymph flow, 379, 388, 389 kinin system activation, lung, microvascular permeability, 377, 379- E. coli septic sheep 381,387, 388 Esterase stain, leukostasis, quantitative esti- shear rate, 387-388 mation, 45, 49 myocardial depression, 387 Extracorporeal circulation opiates, endogenous, 385, 389 biochemical lung monitoring during CPB, naloxone, 385, 389 95-104 PMNs, 378, 379, 387, 388 apnoe, 96, 98-100, 103-104 prostacyclin, 385 elastase, granulocyte, 96, 97, 100-104 sheep model, 378-380, 384-384 lysozyme, 97, 99-100, 104 T cells, 380, 388 NAG, 97-99, 101-104 thromboxane, 382 PEEP, 96, 98, 100, 103, 104 vascular resistance vena cava superior cf. left atrium, peripheral, 377, 381-382, 385 96-98, 101, 102, 104 systemic, 377 kallikrein system activation during CPB, Endotoxin shock 87 dog model (£. coli), 393-398 MDF release during CPB, 611-619 arterial pressure, systemic and pulmo• see also Cl-esterase inhibitor and elastase nary, 394, 395, 398 release, extracorporeal circulation; Index / 649 Kallikrein-kinin system activation chemotactic domain, 33 during aorto-coronary bypass himdin, 39 (CPB) platelet, response, 35 Extravascular lung water Fibrinogen, catecholamines, multiple trauma, alveolar cell reactions, posttraumatic lung and ARDS, 480-481 failure and ARDS, 510-512 Fibrinopeptide A, 274 burn shock and resuscitation, 548-550 Flow phase, changes in injury, 463, 465-469 eglin, elastase inhibitor, and lung edema, cf. starvation, 465-466 septic pigs, 123 Fluid resuscitation leukotriene generation, Polytrauma pa• burn shock, 543, 544, 552 tients with ARDS, 312-313 ETX shock (£. coli), dog model, 394, see also Microvascular permeability, en- 395, 398 dotoxemia/septic shock microvascular permeability, septic shock, 0-Factor XHa 487-488, 490 Cl-esterase inhibitor and elastase release, FMLP, 166-168, 429 extracorporeal circulation, 108, Free radicals. See Antioxidant entries; Lipid 110 peroxidation entries; Oxygen free rad• prekallikrein activation, 93 icals entries Factor XII (Hageman factor), 159, 162, 539, Galactosamine, 301, 303, 306, 307 540 -sensitized mice, lipid X inhibition of Factor Xllf, prekallikrein activation, 93 LPS neutrophil activation, Factor XIÜ 431-432 Cl-esterase inhibitor, early E. coli septi• see also Ebselen (selenium Compound), cemia, pigs, 142, 144 protection vs. endotoxin shock in eglin, elastase inhibitor, and lung edema, galactosamine-sensitized rodents septic pigs, 122-124 Gamma camera, microvascular permeability, Fatoxidation, flow or catabolic phase of in• septic shock, 487, 491 jury, 464, 465, 469 Gastrointestinal system in MOF, 460, 532 Fatty acids, polyunsaturated, 245-246 Gebexate mesilate, 154-155, 389 4-hydroxynonenal, 246-250 Gentamicin, multitherapy regimen for endo• see also Arachidonic acid entries toxemia, pigs, 222 Fibrin Glasgow Coma Scale, 622 catecholamines, multiple trauma, and Glomerular fibrin deposits, prostacyclin in ARDS, 480-481 ETX shock, 371, 374, 375 deposits, glomerular, prostacyclin in ETX Glucose shock, 371, 374, 375 cardiovascular abnormalities, septic Fibrin-neutrophil interactions, lung micro• shock, 447, 449-451, 454-455 vascular injury, 33-41 injury cf. sepsis, 470-472 HETEs, 40-41 ischemia, small intestine, vascular perfu- leukotriene B4, 40-41 sion, 504-505 neutrophil oxidation, flow or catabolic phase, adherence to endothelium, 40 464-466 aggregation, 39 /3-Glucuronidase,ETX, cause of mediator re• Sequestration, lung, 37-39 lease in sepsis, 379 permeability, increased, 34-35, 39 Glutathione peroxidase, ebselen protection protein exchange, 34, 35, 39 vs. ETX shock in galactosamine-sen• pulmonary lymph flow, 34, 35, 38-40 sitized rodents, 282, 285, 286 thrombin, 33-41 Glutathione, reduced (GSH) 650 / Index antioxidant protection vs. free-radical me- post-perfusion Syndrome, 75, 83, 84 diated myocardial injury, 635-639 «i-Proteinase inhibitor, 83-84 oxygen radical scavengers, Prophylaxis whole body inflammation, 84 and treatment, 261 Granulocytes, mediation of tissue injury, Glycerol, injury cf. sepsis, 472, 473 19-28 Glycogen Phosphorylase a, transmembrane activation and shock lung, 23-24 signaling perturbation, endotoxemia, aggregation, 21-23 rat hepatocyte, 404, 405, 411-413, complement system activation, 20-24 416 endothelial damage after endotoxin acti• Granulocytes (PMNs) vation, 25-28 accumulation in myocardial shock is• and platelets, 26 chemia, 63-70 free iron, 27-28 lidocaine, 65, 67-69 frustrated phagocytosis, 19-20 oxygen free radicals, 64 intravascular activation, 20-21 reperfusion, 65-66 oxygen radicals, 26-28 activation, 253-254, 260 pharmacology, 24-25 oxygen free radicals, LPS generation, Steroids, 24-26 blood, 419, 422, 424, 425 a-1-Proteinase inhibitor, 27 aggregation, antioxidant drugs, 276, 278 GSH (reduced glutathione) aprotinin, cellulareffects, 165-171 antioxidant protection vs. free-radical me- arachidonic acid system activation, iso- diated myocardial injury, 635-639 lated lung, 292, 296-298 oxygen radical scavengers, Prophylaxis oxygen radicals, 296 and treatment, 261 burn shock and resuscitation, 539-540, Hageman factor (factor Xu), 159, 162, 539, 547-549 540 ETX, cause of mediator release in sepsis, Hannover Trauma Scale, 521 378, 379, 387, 388 Heart leukotriene generation, Polytrauma pa• depressant factors, 599-603 tients with ARDS, 311, 314-315 acidosis, 600 limb ischemia and inflammation, 14-15 isolated papillary muscle, 602, 603 aggregation, 11, 16 leucine, 601 -monocyte CSF, 432-433 MDF, 591, 592, 596, 601-604 whole body inflammation, trauma patient nickel, 600 autopsy study, 55, 58 , 601 see also Elastase, granulocyte; Leuko- myocardial depression, physiologic-meta• cyte(s); Neutrophils bolic correlations, septic shock, Granulocytes, mediation of pulmonary mem- 446, 454 brane damage, 75-85 rate ARDS, 75, 76, 78, 83, 84 and atropine, in hypotensive central cardiopulmonary bypass, 76-85 hypovolemia, 629-631 complement activation during, 77-78, ETX shock (E. coli), dog model, 80, 84-85 394-395 elastase release during, 81-83 myocardial dysfunction in sepsis, intrapulmonary Sequestration, 79-81, 574-578, 587 85 stimulant factors in shock, 599-600, MDA levels, 79-80 603-607 oxygen free radical peroxidation, catecholamines and angiotensin U, 79-81, 83-84 603 Index / 651 histamine, 604 dotoxemia, multitherapy regimen, inotropic, 603, 604 pigs MSF, shock-induced, 604-607 Hemorrhage, atropine effect on heart rate, ventricular function 629, 630 hypovolemic-traumatic shock, 561, Heparin, extracorporeal circulation 567 Cl-esterase inhibitor and elastase release, multitherapy regimen for endotox• 108 emia, 230,231, 233 kallikrein-kinin system activation during physiologic-metabolic correlations, CPB, 87-89, 91 septic shock, 444 Hepatitis, ebselen protection vs. ETX shock see also Cardiac Output; Hemodynamics; in galactosamine-sensitized rodents, Myocardial entries; Nickel re• 281,284, 285 lease, endogenous, myocardial Hepatocytes. See Transmembrane signaling damage perturbation, endotoxemia, rat Heart Performance evaluation, hypovolemic- hepatocyte traumatic shock, 561-570 HETE and HPETE, 40-41, 334 cardiodynamics, Schema, 562-563 Hip surgery, methylmethacrylate cement in, closed-loop feed-back control circuits, 6 561,569 Hirudin and thrombin, lung microvascular Computers, 568 injury, 39 contractility, 567, 569 Histamine, 162, 212, 227 myocardium Performance, 561 antihistamine in multitherpy regimen for Separation of control circuits, 569 endotoxemia, pig, 212, 213, 222, isolated heart-lung preparation, 228 569-570 heart Stimulation, 604 ventricular Performance, 561, 567 leukotrienes and lipid mediators in ARDS Hemodialysis, MOF, 460, 461 pathogenesis, 318, 321, 322 Hemodynamics Hospital Trauma Index, 56 aprotinin and Cl-esterase inhibitor infu• HPLC. See Chromatography, HPLC sion and pancreatic shock, pig, 5HT. See Serotonin 193-195 Hydrogen peroxide arachidonic acid system activation, iso• injury lated lung, 289-298 cultured cells, 253-254 PAP, 292-295 lung, 238-249 BW755C in endotoxemia, 356-357 -myeloperoxidase, oxygen free radicals, ebselen protection vs. ETX shock in gal- LPS generation, blood, 422 actosamine-sensitized rodents, Hydroxyl radical, oxygen free radicals and 282-283 lung injury, 238-241 ibuprofen, 327-328 and iron chelators, 239-240 kallikrein-kinin system activation, lung, 4-Hydroxynonenal, lipid peroxidation prod- E. coli septic sheep, 135, 137 ucts, cytotoxic, rat liver microsomes, MDF release during CPB, 612-616, 246, 248-250 618-619 Hyperdynamic/hypermetabolic State PGE, administration in ARDS, 363-365 MOF, wound inflammatory mediators see also Hyperdynamic/hypermetabolic and, 525-526, 531-532 State; Trypsin-induced shock, sepsis Syndrome, 526-528, 533-534 hemodynamics and proteolysis, myocardial dysfunction in sepsis, 574, pigs; Vascular entries; under En• 584, 585, 587 652 / Index physiologic-metabolic correlations, septic Multiple organ failure, wound in• shock, 404-442, 454 flammatory mediators; under Is• Hypovolemic shock. See Heart Performance chemia evaluation, hypovolemic-traumaticsh- Inhalation injury. See under Burn shock and ock; Inotropic plasma substances, resuscitation LMW, prolonged hypovolemic poly- Injury Severity Score, 622 traumatic shock, dog whole body inflammation, trauma patient Hypoxia, alveolar, arachidonic acid system autopsy study, 56-57 activation, isolated lung, 294-295 Inositol phospholipid turnover, transmem- brane signaling perturbation, endotox• Ibuprofen, 378, 389 emia, rat hepatocyte, 401-404, MOF, wound inflammatory mediators 407-409, 416 and, 534 Inotropic plasma substances,LMW, pro• see also BW755C (NSAID) effect on longed hypovolemic polytraumatic endotoxemia shock, dog, 591-596 Ibuprofen effect on ETX-stimulated inflam• calcium-binding, 596 mation, 333-344 HPLC, reverse phase, 594 arachidonic acid and eicosanoids, 334, cf. myocardial depressant factor, 591, 342, 344 592, 596 body temperature, 340-341 and papillary muscle, guinea pig bioas- cardiac index, 338, 340 say, 592, 595 cyclooxygenase inhibition, 334, 344 sodium Chloride, 591-594 general NSAID mechanism, 334 see also Myocardial depressant factor lymph flow, 334, 335, 337, 344 Insulin, flow or catabolic phase, 466-469, microvascular permeability, 340, 342, 472 343 Interleukin-1 neutropenia, 333-334, 340 changes in injury, 463, 469, 472 oxygen consumption, 337, 339-341, 344 MOF, wound inflammatory mediators plasma volume, 337 and, 531-534 prophylactic/therapeutic, 335 Protease inhibitors in endotoxemia, 150 pulmonary vascular tone, 336 Interleukin-2, 447 systemic vascular resistance, 337, 338, Intestinal ischemia, vascular perfusion, rat, 340,344 503-507 Immunoelectrophoresis, rocket, 177, 180 Intravascular activation, granulocyte media• Infant respiratory distress Syndrome, 517, tion of tissue injury, 20-21 521 IP3, transmembrane signaling perturbation, Inflammation, whole body endotoxemia, rat hepatocyte, 413-415 granulocyte mediators of pulmonary Iron membrane damage, 84 ADP-, lipid peroxidation products, cyto- trauma patient autopsy study, 55-60 toxic, rat liver microsomes, complement, 59-60 247-249 liver, 58 antioxidant drugs, 272 MOF and ARDS, 55-60 chelators, oxygen free radicals and lung organ weights, 56-60 injury, 239-240 PMNs, 55, 58 free, granulocyte mediation of tissue in• thromboplastin and DIC, 59 jury, 27-28 see also BW755C (NSAID) effect on en• Ischemia dotoxemia; Ibuprofen effect on limbs, C3a and C5a as mediators of in• ETX-stimulated inflammation; flammation, 11-17 Index / 653 ARDS, 11 Kallikrein-kinin system activation during bilirubin (liver function), 11, 13-15, aorto-coronary bypass (CPB), 87-93 17 aprotinin, 87-89, 91,93 Creatinine (kidney function), 13-15, Cl-esterase inhibitor, 89, 92, 93 17 extracorporeal circulation, 87 granulocytes, 14-15 heparin, 87-89, 91 granulocytes, aggregation, 11, 16 kallikrein, 87-90, 92 oxygen radicals, 15 inhibition, 87-89, 91-93 platelets, 14-16 kininogen, HMW, 87-90 respiratory function, 11, 13-15, 17 prekallikrein, 87-90, 93 myocardial shock-, granulocyte accumu- activators, 93 lation, 63-70 Kallikrein-kinin system activation, lung, reperfusion, 65-66 E. coli septic sheep, 133-138 -reperfusion, antioxidant protection vs. antithrombin m, 134, 136-138 free-radical mediated myocardial bradykinin, 137-138 injury, 634-639 hemodynamics, 135, 137 Isoproterenol, myocardial dysfunction in sep• kallikrein inhibition, 134, 136-137 sis, 577, 578 lymph flow, 134, 135, 137 prekallikrein, 134, 136, 137 Kallikrein Prothrombin, 134, 136-138 aprotinin and Cl-esterase inhibitor infu• Ketanserin, multitherapy regimen for endo• sion and pancreatic shock, pig, toxemia, pigs, 212, 213, 222, 228 194, 196-200 Kidney inhibition, 193, 194, 196, 197, 199 aprotinin, very high dosage, Polytrauma, aprotinin inhibition, very high dosage, 180-182 Polytrauma, 175-181 Creatinine, 181 infusion, kinin-induced pathology in urine Output, 180-181 ARDS development, pig, 127-130 function (Creatinine), limb ischemia, C3a bolus injection cf. continuous infu• and C5a as mediators of inflamma• sion, 128-129 tion, 13-15, 17 trypsin-induced shock, hemodynamics glomerular fibrin deposits, prostacyclin in and proteolysis, 185-188, 191 ETX shock, 371, 374, 375 inhibition, 186, 189, 191 MOF, 460-462 Kallikrein-kinin system Kinin aprotinin and Cl-esterase inhibitor, aprotinin and Cl-esterase inhibitor infu• 159-163 sion and pancreatic shock, pig, arachidonic acid system, isolated lung, 199 289, 291-292 -induced pathology in ARDS develop• catecholamines, multiple trauma, and ment, kallikrein infusion, 127-130 ARDS, 477 inhibition, Cl-esterase inhibitor and elas• inhibition, Cl-esterase inhibitor and elas• tase release, extracorporeal circu• tase release, extracorporeal circu• lation, 107-110, 113 lation, 107-110, 113 see also Kallikrein-kinin entries multitherapy regimen for endotoxemia, Kininogen pigs, 212-215, 220-221, 227 aprotinin and Cl-esterase inhibitorinfu- Protease inhibitors in endotoxemia, 149, sion and pancreatic shock, pig, 152-153 199 see also specific components ARDS, pig, 127-129 654 / Index HMW fibrin-neutrophil interactions, lung mi• aprotinin and Cl-esterase inhibitor, crovascular injury, 40-41 159, 161-162 MOF, wound inflammatory mediators during CPB, 87-90 and, 531 Krebs-Henseleit Solution, 503-507 Leukotrienes and lipid mediators in ARDS Kupffer cells, 534 pathogenesis, 317-324 andC5a, 317, 318, 320-324 Lactate and neutrophils, 324 ETX shock (£. coli), dog model, 394, and smooth muscle contraction, 396, 397 321-322 physiologic-metabolic correlations, septic histamine, 318, 321, 322 shock, 446, 452 PAF, 317-323 Lactoferrin, 510 chemical structure, 318, 319, 321 LAMS Computer Software, 335, 337 Schema, 324 Langendorff perrused hearts, myocardial vascular permeability, 320-322 dysfunction in sepsis, 577 Leukotrienes asmediators of ETX shock and Leucine, heart depressant factor, 601 tissue trauma, rat, 301-307 Leukocyte(s) cysteinyl, 303-307, 323 BW755C in endotoxemia, 347-350, 352, hepatobiliary elimination inhibited by 353, 357 ETX, 304-305, 307 count, Cl-esterase inhibitor, early E. coli LPS, pathogenesis mechanism, 306-307 septicemia, pigs, 143, 145 prostacyclin in ETX shock, 370, 372, Leukotrienes, generation, Polytrauma pa• 375 tients with ARDS, 311-316 see also Elastase-approteinase inhibitor bronchoalveolar lavage, 312-314 complex, and leukocyte counts, extravascular lung water, 312-313 septic pig lung; Granulocytes en• granulocytes, 311, 314-315 tries; Neutrophils HPLC, 312, 313 Leukocytosis, MOF, wound inflammatory RIA, 312, 313 mediators and, 530-531 Lidocaine, granulocyte accumulation in myo• Leukostasis, quantitative estimation, post- cardial shock ischemia, 65, 67-69 traumatic lung cf. controls, 43-51 Limb ischemia. See under Ischemia ARDS and MOF, 50 Lipid(s) degranulation, 48-49 cardiovascular abnormalities, septic dogs, 43-45, 50 shock, 447, 452-455 reinfusion, 44, 48, 50 fat oxidation in injury, 464, 465, 469 elastase, 50 see also Leukotrienes and lipid mediators esterase stain, 45, 49 in ARDS pathogenesis human autopsy cases, 45-49 Lipid peroxidation, 274, 275 diagnoses, 46-47 antioxidant protection vs. free-radical me- labeling, 44, 45, 48, 50-51 diated myocardial injury, 633-639 Leukotrienes MDA, 635, 636 alveolar cell reactions, posttraumatic lung oxygen free radicals and lung injury, failure and ARDS, 510-512 239-241 arachidonic acid system activation, iso- Lipid peroxidation products, cytotoxic, rat latedlung, 291,293,296 liver microsomes, 245-250 ebselen protection vs. ETX shock in gal- ADP-iron, 247-249 actosamine-sensitized rodents, aldehyde, 245-248 281,284-286 malondialdehyde, 247, 249 Index / 655 HPLC, 246, 247 Lungs PUFAs, 245, 246 aprotinin, very high dosage, Polytrauma, 4-hydroxynonenal, 246, 248-250 180,182 toxic second messengers, 249 biochemical monitoring during CPB, Lipid X inhibition of LPS neutrophil activa• 95-104 tion, 427-434 infant RDS, 517, 521 ETX receptor competition, 434 lipid X inhibition of LPS neutrophil acti• galactosamine-sensitized mice, 431-432 vation, 431,433 lungs, 431,433 MOF,460-462 cf. other lipid A monosaccharide deriva• tives, 427, 429, 430, 432 phospholipid profile, ARDS in Poly• oxygen free radicals, 427, 432 trauma patients, 517-521 Superoxide, 427-429, 431 postperfusion, 100, 102, 104 Lipopolysaccharide, 378, 380, 385, 387, 389 Surfactant leukotrienes as mediators of ETX shock ARDS, 517, 520 and tissue trauma, 306-307 phospholipids, burn shock and resus• see also Lipid X inhibition of LPS neu• citation, 550-551 trophil activation; Oxygen free ventilatory management, 455, 551 radicals, LPS generation, fresh hu• see also Alveolar entries; Arachidonic man blood acid system activation, isolated Lipoxygenäse inhibition, BW755C in endo• rabbit lung; ARDS (adult respira• toxemia, 302, 347, 358 tory distress sydrome); Eglin, Liver elastase inhibitor, influence on cirrhosis, PGEj administration in ARDS, lung edema, septic pigs; Elastase- 365 ot\ -proteinase inhibitor complex, cysteinyl leukotriene elimination inhibited and leukocyte counts, septic pig by ETX, 304, 305, 307 lung; Fibrin-neutrophil interac- ebselen protection vs. ETX shock in gal• tions, lung microvascular injury; actosamine-sensitized rodents Granulocytes, mediation of pulmo• enzymes, 283, 284, 286 nary membrane damage; Leukos- toxicity, 284 tasis, quantitative estimation, function, limb ischemia, C3a and C5a as posttraumatic lung cf. controls; mediators of inflammation, 11, Oxygen free radicals and lung in• 13-15, 17 jury, rat; Pulmonary entries; Res• MOF, 460, 462 piratory entries Kupffer cell, 534 Lymph flow wound inflammatory mediators and, 534 BW755C in endotoxemia, 347, 349, 353- whole body inflammation, trauma patient 355, 357 autopsy study, 58 ETX, cause of mediator release in sepsis, see also Lipid peroxidation products, cy- 379, 388, 389 totoxic, rat liver microsomes; ibuprofen and ETX-stimulated inflamma• Transmembrane signaling pertur• tion, 334, 335, 337, 344 bation, endotoxemia, rat kallikrein-kinin system activation, lung, hepatocyte E. coli septic sheep, 134, 135, 137 Lucigenin, oxygen free radicals, LPS genera• microvascular permeability, septic shock, tion, blood, 420, 422, 425 490 Luminol, oxygen free radicals, LPS genera• MOF, wound inflammatory mediators tion, blood, 420-424 and, 531 656 / Index pulmonary, fibrin-neutrophil interactions, see also Hypodynamic/hypermetabolic lung microvascular injury, 34, 35, State; Septic shock, physiologic 38-40 and metabolic correlations, Lysophosphatidylcholine, ARDS in Poly• humans trauma, 519-521 Methylmethacrylate cement in hip surgery, 6 Lysosomal enzymes, extracorporeal circula• Methylprednisolone tion, biochemical lung monitoring MDF release during CPB, 611, 613-615, during CPB, 95, 96, 102-103 617-618 lysozyme, 97, 99-100, 104 multitherapy regimen for endotoxemia, NAG, 97-99, 101-104 pigs, 212, 213, 220-222, 228 see also Elastase, granulocyte cf. PBN, oxygen radical scavengers, Pro• Lysozyme, 97, 99-100, 104 phylaxis and treatment, 263, 268 Microsomes. See Lipid peroxidation prod- Macaca mulatta, 115 ucts, cytotoxic, rat liver microsomes «2-Macroglobulin, 92, 199 Microvascular injury. See Fibrin-neutrophil binding, trypsin-induced shock, hemody• interactions, lung microvascular namics and proteolysis, 191 injury Cl-esterase inhibitor, early E. coli septi• Microvascular permeability, endotoxemia/ cemia, pigs, 142, 143, 145 septic shock, 347-352, 357, 487^91 eglin, elastase inhibitor, and lung edema, albumin flux, labeled, E. coli septic septic pigs, 122-124 shock, 490-491 Protease inhibitors in endotoxemia, 151 ARDS, 487 Macrophage(s) BW755C, 348, 354, 357 and complement in shock, 5 ETX, cause of mediator release in sepsis, -like cell line P388D,, oxidant injury, 377, 379-381, 387, 388 254-256 shear rate, 387-388 myocardial dysfunction in sepsis, 587 fluid resuscitation, 487-488, 490 Malondialdehyde (MDA) gamma camera, 487, 491 antioxidant protection vs. free radical me- ibuprofen and ETX-stimulated inflamma• diated myocardial tion, 340, 342, 343 injury, 635-636 leukotrienes and lipid mediators in formation, and antioxidant drugs, 276, ARDS, 320-322 278 lymph flow, 490 granulocyte mediators of pulmonary plasma volume, 489-490 membrane damage, CPB, 79-80 Protease inhibitors, 150-151 rat liver microsomes, 247, 249 transcapillary escape rate, 489 Membrane Mitochondria, 253, 260, 267 damage. See Granulocytes, mediation of MOF. See Multiple organ failure entries pulmonary membrane damage; Monitoring. See under Extracorporeal Lipid peroxidation entries circulation stabilization, ibuprofen, 329 Mortality, Ni release, myocardial damage, Mercaptopropionylglycine, 276 623 Mesenteric artery, superior, ischemic small a-MPG, 276 intestine, vascular perfusion, 503 MTDQ-DA, 633, 636, 639 Metabolic control changes in injury, 463-474 Multiple organ failure (MOF, MSOF) flow or catabolic phase, 463, 465-469 and complement in shock, 3, 4, 7 cf. starvation, 465-466 ARDS, 4, 6 cf. sepsis, 465, 469-472 leukostasis, quantitative estimation, 50 Index / 657 physiologic-metabolic correlations, septic smooth, contraction, leukotrienes and shock, 442,443, 451,455 lipid mediators in ARDS patho• septic patients, 459-462 genesis, 321-322 whole body inflammation, trauma patient see also Myocardial entries autopsy study, 55-60 Myeloperoxidase, 422, 510 Multiple organ failure, wound inflammatory Myocardial depressant factor, 591, 592, 596, mediators, 525-535 601-604 ARDS, 534 inotropic, 602 burns, 525, 526, 528, 532 release during CPB, 611-619 infected cf. uninfected, 527 aprotinin effect, 611, 613-615, ETX, 527-532, 534 617-618 Gl permeability, 532 effects, 616-617 Prostaglandins, 529-530, 532, 534, hemodynamics, 612-616, 618-619 535 methylprednisolone effect, 611, recurrent low-dose endotoxemia, 613-615, 617-618 hemodynamics, 528-529, 531 postperfusion Syndrome, 616 thromboxanes, 529-531 Myocardial dysfunction in sepsis, rat, hyperdynamic, hypermetabolic State, 573-587 525-526, 531-532 jS-adrenergic Stimulation, 576-577 sepsis Syndrome, 526-528, 533-534 isoproterenol, 577-578 interleukin-1, 531-534 calcium homeostasis, altered, 579, 581, leukocytosis, 530-531 583, 584, 587 leukotrienes, 531 cardiac Output, 575, 579, 584 liver, 534 chronotropic effects, 576-578 lymph flow, 531 contractility, 574, 576, 579, 581. 584 mediators listed, 527 endotoxin, 387, 576, 584 oxygen consumption, 525-527, 532 cell membrane effect, 576 prevention, 534-535 heart rate, 574-578, 587 ibuprofen, 534 hyperdynamic, hypermetabolic State, 574, sheep, 527, 531 584, 585, 587 Multiple trauma. See Aprotinin, very high Langendorff perfused hearts, 577 dosage, Polytrauma; Catecholamines, left atrial filling pressure, 580 multiple trauma, and ARDS; Inotropic macrophage, 587 plasma substances, LMW, prolonged oxygen consumption, 579, 585, 586 hypovolemic polytraumatic shock, phosphate inadequacy, 579, 585 dog; Leukotrienes, generation, Poly• physiologic-metabolic correlations, septic trauma patients with ARDS; Phospho• shock, 446, 454 lipid lung profile, ARDS in stroke volume, 574-576 Polytrauma patients ventricular Performance, 573, 577, 579, Multitherapy regimen. See Endotoxemia, 581, 582 multitherapy regimen, pigs compliance, 581 Muscle see also Antioxidant protection vs. free papillary, 592, 595, 602, 603 radical mediated myocardial in• P02, oxygen and blood flow, regional jury, dogs; Nickel release, endoge- differences in early sepsis, 495, nous, myocardial damage; under 496, 501 Granulocytes (PMNs) skeletal, cardiovascular abnormalities, Myocardial Performance, hypovolemic-trau• septic shock, 447-449 matic shock, 561 658 / Index Myocardial Stimulation factor, shock-in- Oxidant injury of cultured cells, 253-258 duced, 604-607 ARDS, 253 and ATP content, 254 NAD, 255-257 bovine aortic endothelial cells, 254-255 NADPH oxidase, 253, 260 DNA, SSB, 256-257 Naja naja cobra, 236-240 H202, 253-254 Naloxone, 212, 213, 227, 228, 385, 389 mouse macrophage-like cell line P388D], Neutropenia 254-256 dialysis-associated, 21 ibuprofen and ETX-stimulated inflamma• and NAD content, 255-257 tion, 333-334, 340 poly-ADP-ribose Polymerase, 255-257 Neutrophils Oxidative inactivation, arproteinase inhibi• chemiluminescence, alveolar cell reac• tor, injected vs. aerosolized, 203-204 tions, posttraumatic lung failure Oxygen and ARDS, 510-511 consumption, 337, 339-341, 344, 500 leukotrienes and lipid mediators in ARDS MOF, wound inflammatory mediators pathogenesis, 324 and, 525-527, 532 oxygen free radicals and lung injury, myocardial dysfunction in sepsis, 579, 235-239 585, 586 Proteinase release, 238-239 physiologic-metabolic correlations, d\ -Proteinase inhibitor bioavailability, in- septic shock, 444, 454 jected vs. aerosolized, 203-204 delivery and consumption, PGEi admin- see also Fibrin-neutrophil interactions, istration in ARDS, 361, 364-367 lung microvascular injury; Granu• pressure locytes entries; Lipid X inhibition alveolo-arterial difference (AaD02), of LPS neutrophil activation posttraumatic lung failure and Nickel release, endogenous, myocardial ARDS, 510 damage, 600, 621-626 partial, 495-497, 501, 504-505 burns, 622 tension/saturation, multitherapy regimen cause of death, 623 for endotoxemia, 232, 233 ECG records, 621-623, 625 Oxygen and blood flow, regional differences, EM, 622, 625 early sepsis, 495-502 serum levels, 621, 624 arterial blood pressure, 501 Nitrogen loss, flow or catabolic phase, arterial oxygen transport, 499 465-469 cardiac Output, 496, 498 No reflow phenomenon, 63 maldistribution, 501-502 Norepinephrine, multiple trauma, and POz, 495-497 ARDS, 478, 483-486 muscle, 495-496, 501 NSAID mechanism, 334; see also BW755C Oxygen free radicals (NSAID) effect on endotoxemia; Ibu• arachidonic acid system activation, iso- profen entries lated lung, 296 ETX, cause of mediator release in sepsis, Opiates, endogenous (endorphins), 212, 227, 379, 380 385, 389 granulocyte Organ failure. See Multiple organ failure accumulation in myocardial shock is• entries chemia, 64 Organ weights, whole body inflammation, mediation of tissue injury, 26-28 trauma patient autopsy study, 56-60 limb ischemia, C3a and C5a as mediators Ouabain, 581, 583 of inflammation, 15 Index / 659 lipid X inhibition of LPS neutrophil acti• vation, 427, 432 MOF, 461 peroxidation, granulocyte mediators of see also Aprotinin and Cl-esterase inhibi• pulmonary membrane damage, tor infusion and pancreatic shock, CPB, 79-81, 83, 84 Pig MDA levels, 79-80 Papillary muscle, 595, 595, 602, 603 Protease inhibitors in endotoxemia, Parenteral nutrition, injury cf. sepsis, 470 150-151 Partial oxygen pressure (PO2) see also Lipid peroxidation entries; Oxi• ischemia, small intestine, vascular perfu- dant injury of culturedcells sion, 504-505 Oxygen free radicals and lung injury, rat, regional differences in early sepsis, 235-241 495-497 catalase, 238, 240, 272, 274 muscle, 495, 496, 501 cobra venom factor, 236-240 PBN, oxygen radical scavenger, Prophylaxis complement, 235-238 and treatment, 261-268 endothelial cells, 236, 238 PEEP, burn shock and resuscitation, 551 H202, 238-239 Permeability, Gl, MOF, 532; see also Micro• hydroxyl radical, 238-241 vascular permeabüity, endotoxemia/ and iron chelators, 239-240 septic shock lipid peroxidation, 239-241 Peroxidation, lipid. See Lipid peroxidation neutrophils, 235-239 entries Proteinase release, 328-239 platelets, 235-236 PH SOD, 238, 272, 274 heart depressant factor, acidosis, 600 Superoxide radical, 238-239 ischemia, small intestine, vascular perfu- Oxygen free radicals, LPS generation, fresh sion, 504-505 human blood, 419-425 Phagocytosis chemiluminescence, 420-422 aprotinin, cellular effects, 169, 171 lucigenin, 420, 422, 425 frustrated, granulocyte mediation of tis• luminol, 420-424 sue injury, 19-20 Superoxide radical, 422 Phenyl-t-butyl-nitrone (PBN), oxygen radical PMN activation, 419, 422, 424, 425 scavenger, Prophylaxis and treatment, Oxygen free radical scavengers, Prophylaxis 261-268 and treatment of experimental shock, Phosphate inadequacy, myocardial dysfunc• rat, 259-268 tion in sepsis, 579, 585 ETX, 262-264 Phosphatide acid PBN, 261-268 ARDS in Polytrauma, 519, 521 electron spin reponse, 261, 262, transmembrane signaling perturbation, 267-268 endotoxemia, rat hepatocyte, 402, cf. methylprednisolone, 263, 268 404, 408 reduced glutathione, a-tocopherol, SOD, Phosphatidylcholine, phosphatidylethanol- 261 amine, 519-521 SMAO, 262-264 Phosphatidylglycerol, 517-521 trauma, 262-267 Phosphatidylinositol see also Antioxidant entries ARDS in Polytrauma, 517, 519-521 PAF, 317-323 transmembrane signaling perturbation, endotoxemia, rat hepatocyte, 402- chemical structure, 318, 319, 321 404, 408, 409, 416 Pancreatitis, 127, 128, 130 Phosphatidylserine, 519, 521 Phospholipase 660 / Index A2, 170 Poly-ADP-ribose Polymerase andoxidant in• C, transmembrane signaling perturbation, jury, 255-257 endotoxemia, rat hepatocyte, 404, Polytrauma scale, 510; see also Multiple 407 trauma Phospholipid lung profile, ARDS in Poly• Poiyunsaturated fatty acids, 245-246 trauma patients, 517-521 4-hydroxynonenal, 246-250 bronchoalveolar lavage, 518, 520 see also Arachidonic acid entries HPLC, 517-519, 521 Postperfusion Syndrome, 75, 83, 84 cf. infant RDS, 517, 521 lung, 100, 102, 104 and Surfactant abnormality, 517, 520 MDF release during CPB, 616 PIP and PIP2, transmembrane signaling per• Prazosin, 407 turbation, endotoxemia, rat hepato• Prekallikrein cyte, 404, 407, 409, 414 Cl-esterase inhibitor Pituitary, 479 and aprotinin, 159, 161-162, 194, Plasma 196, 199, 200 eglin, elastase inhibitor, and lung edema, early E. coli septicemia, pigs, 142, septic pigs, 122-123 143, 145 volume and elastase release, extracorporeal burn shock and resuscitation, 540-542 circulation, 107-109, 113 microvascular permeability, septic during CPB, 87-90, 93 shock, 489, 490 lung, E. coli septic sheep, 134, 136 see also Inotropic plasma substances, trypsin-induced shock, hemodynamics LMW, prolonged hypovolemic and proteolysis, 186, 188 polytraumatic shock see also Kallikrein-kinin system entries Plasmin inhibition, aprotinin, very high dos• Promethazin, multitherapy regimen for endo• age, Polytrauma, 179 toxemia, pigs, 212, 213, 222, 228 Platelet(s) Propyl-gallate, 276 activating factor, 317-323 Prostacyclin, 385 chemical structure, 318, 319, 321 Prostacyclin,intravenous, in endotoxin aggregation, PGEi administration in shock, rabbit, 369-375 ARDS, 367 cyclooxygenase product, 369-370 aprotinin glomerular fibrin deposits, 371, 374, 375 cellular effects, 165, 170, 171 hemodialysis product, 371, 373-375 and Cl-esterase inhibitor, plasma kal• leukocytes, 370, 372, 375 likrein-kinin system activation, PGI2 infusion, 362-375 160 platelets, 370-375 BW755C in endotoxemia, 348, 351 and thromboxane, 369-375 Cl-esterase inhibitor, early E. coli septi• vasodilation, 369 cemia, pigs, 144 Prostaglandin Ei administration in ARDS, granulocyte mediation of tissue injury, 26 septic and post-surgery patients, limb ischemia, C3a and C5a as mediators 361-367 of inflammation, 14-16 cardiac index, 363, 365-367 oxygen free radicals and lung injury, cardiac Output, 361 235-236 cirrhosis, 365 prostacyclin in ETX shock, 370-375 hemodynamics, 363-365 and thrombin, lung microvascular injury, oxygen delivery and consumption, 361, 35 364-367 PMNs. See Granulocytes entries plateletaggregation, 367 Index / 661 pulmonary vascular resistance, 363, Pseudomembranes, inhalation injury, 547 365-367 Pseudomonas, 378 trial, 361-366 aeruginosa, 295 vasoconstriction, 366 Pulmonary artery pressure Prostaglandins, 15, 16, 212, 222, 305, 307 arachidonic acid system activation, iso- arachidonic acid system activation, iso- lated lung, 292-295 lated lung, 289, 291, 294-296 BW755C in endotoxemia, 353, 357 flow or catabolic phase, 469 ETX shock (E. coli), dog model, 394, MOF, ETX and, 529-530, 532, 534, 535 395, 398 PGI2 infusion in ETX shock, 372-375 multitherapy regimen for endotoxemia, Protease inhibitors in endotoxemia, 149-155 hemodynamics, 230 arantiprotease, 151-152 Pulmonary capillary wedge pressure, 232 blood coagulation cascade, 153-154 Pulmonary compliance, burn shock and re• Cl-esterase inhibitor, 153 suscitation, 550 interleukin-1, 150 Pulmonary edema, Cl-esterase inhibitor, kallikrein-kinin system, 149, 152-153 early E. coli septicemia, pigs, 144; a2-macroglobulin, 151 see also Eglin, elastase inhibitor, in- microvascular permeability, 150-151 fluence on lung edema, septic pigs neutrophils, oxygen free radicals and lung Pulmonary lymph flow, fibrin-neutrophil in• injury, 238-239 teractions, lung microvascular injury, oxygen free radicals, 150-151 34, 35, 38-40 proteases in endotoxemia, 149-151 Pulmonary membrane damage. See under see also Endotoxemia, multitherapy regi• Granulocytes, mediation of pulmonary men, pigs; specific proteases and membrane damage inhibitors Pulmonary vascular resistance. See under arProteinase inhibitor, 151-152, 253 Vascular resistance deficiency, 207 Pulmonary vasculartone, ibuprofen and granulocyte mediation of tissue injury, 27 ETX-stimulated inflammation, 336 pulmonary, 83-84 Pyruvate dehydrogenase, cardiovascular ab- oc\ -Proteinase inhibitor bioavailability, in- normalities, septic shock, 447-449, jected vs. aerosolized, dogs, 203-209 451-452 ARDS, 203-204 bronchoalveolar lavage, 203-205 Quin-2, calcium measurement, 405 bronchoscopy, 205 neutrophils, 203-204,207 Radioimmunoassay, leukotriene generation, oxidative inactivation, 203-204 Polytrauma patients with ARDS, 312, pulmonary penetration, 204-209 313 Protein exchange, fibrin-neutrophil interac• Regional flow. See Oxygen and blood flow, tions, lung microvascular injury, 34, regional differences, early sepsis 35, 39 Reperfusion Protein kinase C, transmembrane signaling granulocyte accumulation in myocardial perturbation, endotoxemia, rat hepato• shock ischemia, 65-66 cyte, 403 ischemia-, antioxidant protection vs. free Proteolysis inducing factor, 447; see also radical mediated myocardial in• Trypsin-induced shock, hemody• jury, 634-639 namics and proteolysis, pigs Resistance. See Vascular resistance Prothrombin, kallikrein-kinin system activa• Respiratory function, limb ischemia, C3a and tion, lung, E. coli septic sheep, 134, C5a as mediators of inflammation, 11, 136-138 13-15, 17 662 / Index Respiratory quotient, flow or catabolic MOF, 442, 443,451,455 phase, 464, 465 Protease inhibitors, 453 protein reprioritization, 453-454 Salmonella myocardial depression, 446, 454 abortus equi, 282, 421, 423 patterns of sepsis, cf. reference control minnesota, 301, 303 State, 443-446 Scavengers. See Antioxidant entries; Oxygen oxygen consumption, 444, 454 free radical scavengers,prophylaxis ventricular function, 444 and treatment of experimental shock, therapy, 454-456 rat ventilatory management, 455 Second messengers, toxic, lipid peroxidation see also Endotoxin shock products, 249 Serotonin (5HT), 162, 212, 227 Selenium. See Ebselen (selenium Com• antagonist ketanserin, 212, 213, 222, 228 pound), protection vs. endotoxin Signaling. See Transmembrane signaling per• shock in galactosamine-sensitized turbation, endotoxemia, rathepatocyte rodents Simplified Acute Physiologic Score, 622 Sepsis/septicemia Small intestine, ischemia, vascular perfusion, cf. changes in injury, 465, 467-472 503-507 multiple organ failure, 459-462 SMAO, oxygen radical scavengers, Prophy• Syndrome, MOF, wound inflammatory laxis and treatment, 262-264 mediators and, 526-528, 533-534 Sodium Chloride, 591-594 see also Cl-esterase inhibitor, early E. Sphingomyelin, ARDS in Polytrauma, coli septicemia, pigs; Eglin, elas• 519-521 tase inhibitor, influence on lunge- Spin resonance, oxygen radical scavengers, dema, septic pigs; Elastase-ap Prophylaxis and treatment, 261, 262, proteinase inhibitor complex, and 267, 268 leukocyte counts, septic pig lung; Staphylococcal a-toxin, 295-296 Kallikrein-kinin system activation, Starvation cf. flow or catabolic phase of in• lung, E. coli septic sheep; Micro• jury, 465-466 vascular permeability, endotox- Steroids, granulocyte mediation of tissue in• emia/septic shock; Myocardial jury, 24-26; see also specific Steroids dysfunction in sepsis, rat; Oxygen Superoxide dismutase (SOD), 428, 429 and blood flow, regional differ- antioxidant protection vs. free radical ences, early sepsis; Prostaglandin mediated Ei administration in ARDS, septic myocardial injury, 635-639 and post-surgery patients aprotinin, cellular effects, 166 Septic shock, ibuprofen, increased survival, and lung injury, 238, 272, 274 327-330 prophylaxis/treatment, 261 Septic shock, physiologic and metabolic cor• Superoxide radical relations, humans, 439-456 aprotinin, cellular effects, 165, 166, 169 A-D states, 446 lipid X inhibition of LPS neutrophil acti• ARDS, 441, 446 vation, 427-429, 431 cardiac abnormalities, metabolic basis, LPS generation, blood, 422 446-453, 455^56 and lung injury, 238-239 hemodynamics, 440-442, 454 see also Oxygen free radicals entries cardiac Output, 440-442 Surgery, hip, 6; see also Prostaglandin Ei vascular tone, 442, 444 administration in ARDS, septic and lactate, 446, 452 post-surgery patients Index / 663 Survival receptors, 405-406, 415 aprotinin and Cl esterase inhibitor infu• Trauma. See Heart Performance evaluation, sion and pancreatic shock, pig, hypovolemic-traumatic shock; Leu- 193 kostasis, quantitative estimation, post• traumatic lung cf. controls; ibuprofen increases, 327-330 Leukotrienes as mediators of ETX T cells, 380, 388 shock and tissue trauma, rat; Multiple Temperature, body. See Body temperature trauma; under Inflammation, whole Thrombin body catecholamines, multiple trauma, and Trauma scores, catecholamines, and ARDS, ARDS, 479, 480, 485, 486 478, 480, 484 and fibrin-neutrophil interactions, lung Triglyceride abnormalities, septic shock, microvascular injury, 33-41 447, 452^55 Thromboplastin, 59 Trypsin-induced shock, hemodynamics and Thromboxanes, 305, 307 proteolysis, pigs, 185-192 arachidonic acid system activation, iso- blood pressure (MAP), 189-191 latedlung, 291,293-297 cardiac Output, 189-191 burn shock and resuscitation, 541, 548 chromogenic peptide Substrate analysis, BW755C in endotoxemia, 347, 350, 352, 185, 186, 191 355-357 kallikrein, 185-188, 191 ETX, cause of mediator release in sepsis, inhibition, 186, 188, 191 382 a2-macroglobulin Dinding, 191 MOF, ETX and, 529-531 prekallikrein, 186, 188 prostacyclin in ETX shock, 369-375 trypsin, plasma activity, 186, 187 Thromboxane synthetase inhibitors, rat ETX, vascular resistance, systemic, 190-191 328-329 Tyrosine, 442 TNF, 469, 472 a-Tocopherol, 261, 272, 276 Urinary excretion Transferrin, 272, 274 eglin, septic pigs, 122-123 Transmembrane signaling perturbation, en• very high dosage aprotinin, Polytrauma, dotoxemia, rat hepatocyte, 401-416 180-181 aradrenergic receptors, 406-407, 415 Ca2+, 401-405, 409-410, 413-416 Vagal activity, atropine effect on heart rate, IP3-stimulated release, 413-415 629, 631 Quin-2 measurement, 405 Vascular perfusion, intestinal ischemia, rat, cAMP, 402 503-507 cGMP, 402-403 Vascular permeability. See Microvascular epinephrine, 409-412 permeability, endotoxemia/septic glycogen Phosphorylase a, 404, 405, shock 411-413,416 Vascular resistance inositol phospholipid turnover, 401-404, ETX, cause of mediator release in sepsis 407-409 peripheral, 377, 381, 382, 385 phosphatidic acid, 402, 404, 408 systemic, 377 phosphatidylinositol, 402^04, 408- ibuprofen and ETX-stimulated inflamma• 409, 416 tion, 337, 338, 340, 344 PIP and PIP2, 404, 407-409, 414 multitherapy regimen for endotoxemia, protein kinase C, 403 hemodynamics, 216, 218, 219, phospholipase C, 404, 407 230 Vasopressin, 402, 404, 407-412, 415 pulmonary 664 / Index multitherapy regimen for endotox• physiologic-metabolic correlations, septic emia, hemodynamics, 218, shock, 455 220, 230, 231 Ventricular Performance PGE1 administration in ARDS, 363, hypovolemic-traumatic shock, 561, 567 365-367 multitherapy regimen for endotoxemia, systemic, ETX shock (£. coli), dog 230, 231, 233 model, 3%, 397 myocardial dysfunction in sepsis, 573, trypsin-induced shock, hemodynamics 577, 579, 581, 582 and proteolysis, 190, 191 compliance, 581 Vascular tone, physiologic-metabolic corre• physiologic-metabolic correlations in sep• lations, septic shock, 442, 444 tic shock, 444 Vasopressin, 382, 601 Verapamil, 581, 583, 584 transmembrane signaling perturbation, burn shock and resuscitation, 542 endotoxemia, rat hepatocyte, 402, White blood cells. See Leukocyte(s); specific 404, 407-412, 415 types receptors, 405-406, 415 Wound. See Multiple organ failure, wound Vena cava superior, lung monitoring during inflammatory mediators CPB, 96-98, 101, 102, 104 Ventilatory management Xanthine oxidase, 260 inhalation injury, burn shock and resusci• tation, 551 ZAP, 166-168