( AGARD-AG-l43-' ADVISORY GROUP FOR AEROSPACE RESEARCH 81 DEVELOPMENT 7 RUE ANCELLE 92 NEUILLY SUR-SEINE FRANCE I PART I I l '1 . AGARDograph No. 143 . 11 On __ L- -Non-Invasive Technique Assessment \ by - - -- D.M.Denison --\a Parts I and 11 are contained in an overall folder m I DISTRIBUTION AND AVAILABILITY ON BACK COVER AGARDograph No. 143 I NORTH ATLANTIC TREATY ORGANIZATION ADVISORY GROUP FOR AEROSPACE RESEARCH AND DEVELOPMENT (ORGANISATION DU TRAITE DE L'ATLANTIQUE NORD) A NON-INVASIVE TECHNIQUE OF CARDIO-PULMONARY ASSESSMENT ' by D. M. Denison Published in Two Parts PART I TEXT This paper has been sponsored by the Aerospace Medical Panel of AGARD - NATO ACKNOWLEDGMENTS Most of the original work described here was carried out at the R.A.F. Institute of Aviation Medicine, Farnborough Hants., with the help of Wing Commanders J.Ernsting and P.Howard, Squadron Leaders D.Glaister, A.MacMillan and D. Reader, Mr. W.Tonkins and Miss Maris Bradley. The Director-General, Medical Services, R.A.F. (Air Marshal Sir George Gunn) has kindly authorized inclusion of that part in this monograph. The cardiac catheter studies mentioned in Chapter I1 were done with John Ernsting, Peter Howard and Dr. A. Chaloner. Those described in Chapter IV were made with Dr. R.H.Edwards, Dr. G.Jones and Miss Helen Pope in the Department of Medicine at the Royal Postgraduate Medical School, London. The immersion experiments discussed in the last chapter are being carried out at the Department of Medicine of the University of California, San Diego. Some parts of Chapter I1 have been published in the Bulletin de Physio-Pathologie Respiratoire Vo1.3, pp.439-456 1967 and the catheter studies of Chapter IV have been Described in J. Physiol. Vo1.203, pp. 75-76P, 1969, and in Respiration Physiology Vol. 7, pp.326-334, 1969. Otherwise the work has not been published previously. Clearly the experimental studies were made possible by the colleagues named and I am most grateful for their very generous support. Errors of interpretation are mine. 612.17 Published August 1970 Printed by Technical Editing and Reproduction Ltd Harford House, 7-9 Charlotte St. London. VIP IHD ii PREFACE In medicine and physiology it is commonly necessary to penetrate an epithelial surface to discover the nature of a process. Once the process is understood it is often possible to identify an external reflection which allows it to be assessed by non-invasive means. Every field of physiology can provide examples of the sequence of invasive research leading to non-invasive testing. This monograph is concerned with a particular non-invasive test of cardiorespiratory function which has been the subject of little study until recently. There are theoretical reasons for believing,that a detailed knowledge of the gas tensions in mixed venous blood could be most informative but in the past they have attracted little interest because their measurement required cardiac catheterisation. In the last few years the development of rapid and accurate gas analysers has allowed mixed venous gas tensions to be estimated by respiratory means. Because of this technological advance it is worthwhile reviewing what can be learnt from studies of venous blood. The first chapter describes a theoretical exploration of the factors influencing the gas tensions in mixed venous blood, the second chapter tells how they may be measured, the third lists the effects of various cardio-pulmonary stresses and the fourth reviews the theoretically exciting.but controversial work done in this field in the last two years. The present studies have been directed to the effects of respiratory stresses of the sort seen in flying and diving but they are equally applicable to clinical practice. The theoretical analysis is relevant to the management of patients with indwelling catheters, where central venous blood can be sampled directly, as, for example, in and after cardiac surgery. Dans la medecine et la physiologie il est soubent ndcessaire de pdnktrer une surface dpitudliale pour ddcouvrir la nature d’un processus. Une fois compris ce processus, il est frkquemment possible d’ en identifier un reflet exterieur qui permet de l’dvaluer par, des moyens non envahissants. Dans tous les domaines de la physiologie on trouve des cas oh la suite des recherches envahissantes a conduit d l’essai non envahissant. Dans la prdsente monographie il s’agit d‘un essai particulier et non envahissant de la fonction cardio - respiratoire qui, jusque dans ces derniers temps, a &e, trhs peu dtudide. Du c6td thdorique il y a tout lieu de croire que des connaissances ddtailldes concernant les tensions des gaz du sang veineux mixte pourraient fournir des renseignements prkcieux, mais ces tensions ne prdsentaient autrefois que peu d’ interet & cause du fait qu’une cathdtdrisation cardiaque dtait ndcessaire pour les mesurer. La mise au point au cours de ces dernidres anndes d’appareils rapides et prkcis d’analyse des gaz a permis l’estimation des tensions de gaz du sang veineux mixte d l’aide de moyens respiratoires. GrEice A ces progrds technologiques il est utile de passer en revue les enseignements pouvant &re tirds des dtudes sur le sang veineux. Le premier chapitre ddcrit une exploration thdorique des facteurs influant sur les tensions de gaz survenant dans le sang veineux mixte; le deuxihme traite des moyens permettant de les mesurer; le troisidme indique les consdquences de diverses contraintes cardio-pulmonaires et le quatridme fait le point des travaux thdoriquement sensat ionnels mais controversables effectuds dans ce domaine au cours de ces deux dernihres anndes. Les prksentes dtudes ont portd sur les effets de contraintes respiratoires du type de ceux qui ont ktk constat& chez l’aviateur ou le plongeur, mais elles s’appliquent dgalement la pratique clinique. L’analyse thdorique prdsentde est pertinente d la gestion de malades ayant des cathkters intdrieurs, oh il est possible d’ kchantillonner directement le sang veineux central, par exemple, pendant ou aprds les interventions cardiaques. iii NOTATION The abbreviations and symbols used in this thesis have been adapted for typescript from those recommended by Pappenheimer et a1 1950. Their meanings are given below. Volumes of gas are represented by V, flows of gas by V, the inspired gas phases by I and the expireg phase by E. Alveolar values are shown by A. Quantities of blood are symbolised by Q, and of blood flow by Q. Arterial, venous and tissue values are indicated by the minuscules a, v and t. A bar over a symbol so, Z, shows a mean or mixed value. Examples and special cases are: VE expired volume. VE minute volume. expired volume of oxygen. oxygen uptake per minut e. "02 VD the volume of respiratory dead space. VT the tidal volume. VL the volume of the respiratory system. VB the volume of the rebreathing bag. VA alveolar ventilation per minute. the partial pressure of oxygen in the inspirate. the partial pressure of oxygen in mixed expirate. the partial pressure of oxygen in end-tidal expirate. the partial pressure of gas x in alveolar air. arterial oxygen tension. venous carbon dioxide tension. the tension of oxygen in mixed venous blood.. barometric pressure. the partial pressure of CO, in moist inspirate (PI;,, = 47 mm Hg). the fractional concentration of oxygen in dry inspirate. the fractional concentration in moist inspirate, similarly. , arterial oxygen saturation CO2 content of mixed venous blood. CO2 l Q l cardiac output. I 4 a, muscle blood flow. cardiac output estimated from facts about oxygen transfer. $2 Qco, cardiac output calculated from facts about CO, transfer. sv cardiac stroke volume. f respiratory rate (resphin). RV pulmonary residual volume. FRC pulmonary functional residual capacity. X individual value. X mean value SD standard deviation. r correlation coefficient. iv CONTENTS Page ACKNOWLEDGMENTS ii PREFACE iii RESUME iii NOTATION iv CHAPTER I. A USEFUL MODEL OF THE CARDIO-RESPIRATORY SYSTEM 1 Introductory concepts 1 Rest and exercise in normal surroundings 6 The role of the passive homeostats 9 Abnormal surroundings - hypercapnoea 13 - altitude hypoxia 13 Discussion and summary of the theoretical section 14 CHAPTER 11. A REBREATHING METHOD OF MEASURING THE GAS TENSIONS OF MIXED VENOUS BLOOD 15 Introduction 15 Details of the method 16 Results of experiments to check the method 19 Summary of the method 23 CHAPTER 111. THE EFFECTS OF VARIOUS STRESSES UPON THE GAS TENSIONS OF MIXED VENOUS BLOOD 25 Introduction, apparatus and methods 25 Statistical design, calculations 30 Results - adequacy of controls 32 - metabolic gas exchanges 33 - ventilation 33 - perfusion 34 - summary of homeostatic responses 35 , - the changes in venous blood 35 Summary and discussion 36 CHAPTER IV. A REVIEW OF RECENT WORK 39 REFERENCES 41 APPEND X I Tabulated summary of results from Chapter I11 47 Dissociation curve data 52 i Effective dead space 52 i The automatic timer 53 Method of determining resolution of the rebreathing manoeuvre 53 Miscellaneous graphs See Part I1 V 1 CHAPTER I. A USEFUL MODEL OF THE CARDIO-RESPIRATORY SYSTEM. PART 1 This chapter, about the general problems created for tissue respiration by environmental change and disease. began as an armchair exercise to construct a workable model of respiration from a minimum of facts, a diversion enjoyed by many others (Suskind and Rahn 1954, Farhi and Rahn 1955, Rahn and Fenn 1955. Nissen-Meyer 1962. Kreuzer 1966, Shephard 1966, Campbell 1967, Holmgren 1967. and Wasserman et a1 1967). For logical completeness description of the model, and of the conclusions that can be drawn from it, must begin with some banal fundamentals which I apologise for resurrecting. In most cases, little more has been done than to state the obvious within a consistent set of assumptions. One instinctively wonders whether calculations from a hypothetical model have any value when it is simple to measure what actually occurs directly.