DOCSLIB.ORG

Pharmacokinetic and Pharmacodynamic Studies of Three Angiotensin-Converting Enzyme Inhibitors in Healthy Normotensive Horses

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pharmacokinetic and Pharmacodynamic Studies of Three Angiotensin-Converting Enzyme Inhibitors in Healthy Normotensive Horses Department of Animal Medicine and Surgery. Department of Pharmacology, Toxicology and Legal and Forensic Medicine. Equine Sport Medicine Center Faculty of Veterinary Medicine, University of Córdoba, Spain PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES OF THREE ANGIOTENSIN-CONVERTING ENZYME INHIBITORS IN HEALTHY NORMOTENSIVE HORSES MANUEL GÓMEZ DÍEZ Supervisors: Dr. Ana Muñoz Juzado Dr. Juan Manuel Serrano Rodríguez Córdoba, 2017 TITULO: Pharmacokinetic and pharmacodynamic studies of three angiotensin-converting enzyme inhibitors in healthy normotensive horses AUTOR: Manuel Gómez Díez © Edita: UCOPress. 2017 Campus de Rabanales Ctra. Nacional IV, Km. 396 A 14071 Córdoba www.uco.es/publicaciones [email protected] Manuel Gómez Díez Page 2 Angiotensin-converting enzyme inhibitors in the horse TÍTULO DE LA TESIS: PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES OF THREE ANGIOTENSIN- CONVERTING ENZYME INHIBITORS IN HEALTHY NORMOTENSIVE HORSES (Estudios farmacocinéticos y farmacodinámicos de tres inhibidores de la enzima de conversión de la angiotensina en caballos sanos normotensos) DOCTORANDO/A: MANUEL GÓMEZ DÍEZ INFORME RAZONADO DE LOS DIRECTOR/ES DE LA TESIS La presente tesis doctoral ha sido realizada bajo la tutela de dos directores pertenecientes a los Departamentos de Medicina y Cirugía Animal (Dr. Ana Muñoz) y de Farmacología, Toxicología y Medicina Legal y Forense (Dr. Juan Manuel Serrano- Rodríguez), de la Universidad de Córdoba. La tesis se presenta como un compendio de cuatro publicaciones, todas ellas publicadas en revistas indexadas, situadas en el primer tercil, según su índice de impacto y en inglés, al optar a mención internacional. Durante la realización de esta tesis doctoral, el doctorando ha mostrado un gran interés y dedicación al trabajo y ha sido capaz de desarrollar una labor de investigación con rigor científico. Hemos encontrado una importante progresión en cuanto a su capacidad investigadora. La presente tesis ha generado hasta este momento la siguiente producción científica: Page 3 Manuel Gómez Díez Artículos publicados Gómez-Díez M, Muñoz A, Caballero JM, Riber C, Castejón F, Serrano-Rodríguez JM. 2014. Pharmacokinetics and pharmacodynamics of enalapril and its active metabolite, enalaprilat, at four different doses in healthy horses. Research in Veterinary Science, 97(1):105-110. Muñoz A, Esgueva M, Gómez-Díez M, Serrano-Caballero JM, Castejón-Riber C, Serrano-Rodríguez JM. 2016. Modulation of acute transient exercise-induced hypertension after oral administration of four angiotensin-converting enzyme inhibitors in normotensive horses. The Veterinary Journal, 208:33-37. Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Serrano Caballero JM, Muñoz A. 2016. Pharmacokinetics and pharmacodynamics of ramipril and ramiprilat after intravenous and oral doses of ramipril in healthy horses. The Veterinary Journal, 208: 38- 43. Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Ayala N, Caballero JM, Muñoz A. 2017. Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses. Research in Veterinary Science, 114:117-122. Comunicaciones presentadas en congresos Solano E, Muñoz A, Gómez-Díez M, Serrano JM, Granados MM, Ruiz I, Serrano Rodríguez JM. 2012. Concentraciones sanguíneas de enalapril y enalaprilato tras la administración intravenosa de enalaprilo en el caballo. XIII Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Gómez-Díez M, Serrano Rodríguez JM, Serrano Caballero JM, Galán A, Martínez C, Muros A, Muñoz A. 2012. Inhibición de la enzima de conversión de la angiotensina tras la administración de enalaprilo a diferentes dosis en caballos. XIII Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Solano E, Gómez-Díez M, Serrano Rodríguez JM, Serrano Caballero JM, Muñoz A. 2013. Actividad de la enzima de conversión de la angiotensina (ECA) tras la administración de ramiprilo en el caballo. XIV Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Gómez-Díez M, Serrano Rodríguez JM, Serrano Caballero JM, Riber C, Castejón F, Muñoz A. 2013. Angiotensin-converting enzyme (ACE) activity after administration of oral ramipril in horses. 11th Congress of the World Equine Veterinary Association WEVA, Budapest, Hungría. Gómez-Díez M, Muñoz A, Esgueva M, Serrano Caballero JM, Rubio MD, Rodríguez González-Miranda R, Serrano Rodríguez JM. 2014. La administración oral de quinaprilo en el caballo reduce la actividad sérica de la enzima de conversión de la angiotensina más de un 70%. XV Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Esgueva M, Serrano Rodríguez JM, Gómez-Díez M, Serrano Caballero M, Castejón-Riber C, Granados MM, Muñoz A. 2014. El benaceprilo inhibe la hipertensión aguda temporal inducida por ejercicio, pero el enalaprilo no. XV Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Page 4 Angiotensin-converting enzyme inhibitors in the horse Gómez-Díez M, Muñoz A, Serrano Caballero JM, Esgueva M, Castejón-Riber C, Serrano Rodríguez JM. 2015. Actividad comparada de la enzima de conversión de la angiotensina (ECA) tras la administración de inhibidores de la ECA por vía intravenosa y oral en el caballo. XVI Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Además, el doctorando ha colaborado en otros trabajos de investigación del grupo AGR-111 (Medicina Deportiva Equina), en el que se integró. De este modo, ha participado en las siguientes publicaciones: Muñoz A, Riber C, Trigo P, Gómez-Díez M, Castejón FM. 2012. Bacterial endocarditis in two Spanish foals after neonatal septicemia. Journal of Equine Veterinary Science 32:760-766 (T2). Tofé E, Muñoz A, Castejón F, Trigo P, Castejón-Riber C, Gómez-Díez M, Riber C. 2013. Behavior of renin angiotensin aldosterone axis during pulling exercises in euhydrated and dehydrated horses. Research in Veterinary Science, 95(2):616-622 (T1). Muñoz A, Rodríguez RGM, Riber C, Trigo P, Gómez-Díez M, Castejón F. 2013. Subclinical Theileria equi infection and rhabdomyolysis in three endurance horses. Pakistan Veterinary Journal 33(2):256-258 (T1). Muñoz A, Riber C, Gómez-Díez M, Castejón FM. 2013. Interpretación fisiológica y clínica de las pruebas de esfuerzo en el caballo de deporte. Utilidad de la ergoespirometría. Equinus 37:6-23 (sin índice de impacto). Gómez-Díez M, Muñoz A, Castejón F, Santisteban R, Vivo R, Riber C. 2014. Rectal tear with hematoma after accidental breeding as a cause of peritonitis and recurrent colic in a mare. Pakistan Veterinary Journal 34(4):557-559 (T1). Rodríguez R, Cerón JJ, Riber C, Castejón F, Gómez-Díez M, Serrano-Rodríguez JM, Muñoz A. 2014. Acute phase proteins in Andalusian horses infected with Theileria equi. The Veterinary Journal 202:182-183 (T1). y en las siguientes comunicaciones a congresos: Castejón-Riber C, Muñoz A, Roldán J, Trigo P, Gómez-Díez M, Riber C. 2011. Hematology, plasma proteins and fibrinogen in endurance horses completing 500 km in 6 days. 13th Conference of the European Society of Veterinary Clinical Pathology, Dublin, Irlanda. Muñoz A, Riber C, Vivo R, Santisteban R, Tovar P, Agüera S, Rubio MD, Agüera EI, Escribano BM, Trigo P, Castejón-Riber C, Gómez-Díez M, Castejón F. 2011. Investigación en cardiología en el caballo de deporte. Curso de Investigación en Veterinaria y Ciencia y Tecnología de los Alimentos, Córdoba, España. Satué K, Gómez-Díez M, Muñoz A. 2012. Serum triglyceride concentrations during pregnancy in Spanish mares with different body condition scoring. Congreso de la Sociedad Italiana de Veterinarios de Équidos SIVE, Bolonia, Italia. Muñoz A, Riber C, Gómez-Díez M, Castejón-Riber C, Castejón F, Cerón J. 2012. Evolución temporal de las proteínas de fase aguda tras una inflamación inducida por vacunación en el caballo. XIII Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Page 5 Manuel Gómez Díez Gómez-Díez M, Tofé E, Riber C, Castejón F, Muñoz A. 2013. Effect of strength exercise on testosterone, cortisol and muscle enzymes in horses. European Veterinary Conference Voorjaarsdagen, Amsterdam, Holanda. Gómez-Díez M, Riber C, Castejón F, Roldán J, Muñoz A. 2013. Pérdida de rendimiento en competición en un caballo de raid con eritrocitosis absoluta. XIV Congreso Internacional de Medicina y Cirugía Equina, Sevilla, España. Muñoz A, Castejón F, Trigo P, Roldán J, Rubio MD, Gómez-Díez M, Castejón-Riber C, Riber C. 2013. Veterinary clinical examination of endurance horses in competition: correlation with laboratory data. Congreso de la Sociedad Italiana de Veterinarios de Équidos SIVE. Arrezzo, Italia. Gómez-Díez M, Muñoz A, Trigo P, Roldán J, Castejón R, Castejón-Riber C, Riber C. 2013. Response to a 7- day endurance competition in horses with normal and raised serum muscle enzyme activities. Congreso de la Sociedad Italiana de Veterinarios de Équidos SIVE. Arrezzo, Italia. Vega L, Gómez-Díez M, Muñoz A. 2013. Características laboratoriales diferenciales entre caballos de raid exitosos y eliminados por alteraciones metabólicas y extenuación. VIII Jornadas Complutenses, VII Congreso Nacional de Investigación en Ciencias de la Salud para Alumnos de Pregrado y XII Congreso de Ciencias Veterinarias y Biomédicas. Universidad Complutense de Madrid, España. Castejón-Riber C, Muñoz A, Trigo P, Castejón F, Gómez-Díez M, Riber C. 2013. Oxygen uptake and ventilatory thresholds in endurance horses with
Load more

Recommended publications
  • Tolerance and Resistance to Organic Nitrates in Human Blood Vessels
    \ö-\2- Tolerance and Resistance to Organic Nitrates in Human Blood Vessels Peter Radford Sage MBBS, FRACP Thesis submit.ted for the degree of Doctor of Philosuphy Department of Medicine University of Adelaide and Cardiology Unit The Queen Elizabeth Hospital I Table of Gontents Summary vii Declaration x Acknowledgments xi Abbreviations xil Publications xtil. l.INTRODUCTION l.L Historical Perspective I i.2 Chemical Structure and Available Preparations I 1.3 Cellular/biochemical mechanism of action 2 1.3.1 What is the pharmacologically active moiety? 3 1.3.2 How i.s the active moiety formed? i 4 1.3.3 Which enzyme system(s) is involved in nitrate bioconversi<¡n? 5 1.3.4 What is the role of sulphydryl groups in nitrate action? 9 1.3.5 Cellular mechanism of action after release of the active moiety 11 1.4 Pharmacokinetics t2 1.5 Pharmacological Effects r5 1.5.1 Vascular effects 15 l.5.2Platelet Effects t7 1.5.3 Myocardial effects 18 1.6 Clinical Efhcacy 18 1.6.1 Stable angina pectoris 18 1.6.2 Unstable angina pectoris 2t 1.6.3 Acute myocardial infarction 2l 1.6.4 Congestive Heart Failure 23 ll 1.6.5 Other 24 1.7 Relationship with the endothelium and EDRF 24 1.7.1 EDRF and the endothelium 24 1.7.2 Nitrate-endothelium interactions 2l 1.8 Factors limiting nitrate efficacy' Nitrate tolerance 28 1.8.1 Historical notes 28 1.8.2 Clinical evidence for nitrate tolerance 29 1.8.3 True/cellular nitrate tolerance 31 1.8.3.1 Previous studies 31 | .8.3.2 Postulated mechanisms of true/cellular tolerance JJ 1.8.3.2.1 The "sulphydryl depletion" hypothesis JJ 1.8.3.2.2 Desensitization of guanylate cyclase 35 1 8.i.?..3 Impaired nitrate bioconversion 36 1.8.3.2.4'Ihe "superoxide hypothesis" 38 I.8.3.2.5 Other possible mechanisms 42 1.8.4 Pseudotolerance ; 42 1.8.4.
    [Show full text]
  • A Textbook of Clinical Pharmacology and Therapeutics This Page Intentionally Left Blank a Textbook of Clinical Pharmacology and Therapeutics
    A Textbook of Clinical Pharmacology and Therapeutics This page intentionally left blank A Textbook of Clinical Pharmacology and Therapeutics FIFTH EDITION JAMES M RITTER MA DPHIL FRCP FMedSci FBPHARMACOLS Professor of Clinical Pharmacology at King’s College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK LIONEL D LEWIS MA MB BCH MD FRCP Professor of Medicine, Pharmacology and Toxicology at Dartmouth Medical School and the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA TIMOTHY GK MANT BSC FFPM FRCP Senior Medical Advisor, Quintiles, Guy's Drug Research Unit, and Visiting Professor at King’s College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK ALBERT FERRO PHD FRCP FBPHARMACOLS Reader in Clinical Pharmacology and Honorary Consultant Physician at King’s College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK PART OF HACHETTE LIVRE UK First published in Great Britain in 1981 Second edition 1986 Third edition 1995 Fourth edition 1999 This fifth edition published in Great Britain in 2008 by Hodder Arnold, an imprint of Hodden Education, part of Hachette Livre UK, 338 Euston Road, London NW1 3BH http://www.hoddereducation.com ©2008 James M Ritter, Lionel D Lewis, Timothy GK Mant and Albert Ferro All rights reserved. Apart from any use permitted under UK copyright law, this publication may only be reproduced, stored or transmitted, in any form, or by any means with prior permission in writing of the publishers or in the case of reprographic production in accordance with the terms of licences issued by the Copyright Licensing Agency.
    [Show full text]
  • Medical Management of Advanced Heart Failure
    CLINICAL CARDIOLOGY CLINICIAN’S CORNER Medical Management of Advanced Heart Failure Anju Nohria, MD Context Advanced heart failure, defined as persistence of limiting symptoms de- Eldrin Lewis, MD spite therapy with agents of proven efficacy, accounts for the majority of morbidity and mortality in heart failure. Lynne Warner Stevenson, MD Objective To review current medical therapy for advanced heart failure. EART FAILURE HAS EMERGED AS Data Sources We searched MEDLINE for all articles containing the term advanced a major health challenge, in- heart failure that were published between 1980 and 2001; EMBASE was searched from creasing in prevalence as age- 1987-1999, Best Evidence from 1991-1998, and Evidence-Based Medicine from 1995- adjusted rates of myocardial 1999. The Cochrane Library also was searched for critical reviews and meta-analyses Hinfarction and stroke decline.1 Affect- of congestive heart failure. ing 4 to 5 million people in the United Study Selection Randomized controlled trials of therapy for 150 patients or more States with more than 2 million hospi- were included if advanced heart failure was represented. Other common clinical situ- talizations each year, heart failure alone ations were addressed from smaller trials as available, trials of milder heart failure, con- accounts for 2% to 3% of the national sensus guidelines, and both published and personal clinical experience. health care budget. Developments her- Data Extraction Data quality was determined by publication in peer-reviewed lit- alded in the news media increase pub- erature or inclusion in professional society guidelines. lic expectations but focus on decreas- Data Synthesis A primary focus for care of advanced heart failure is ongoing iden- ing disease progression in mild to tification and treatment of the elevated filling pressures that cause disabling symp- moderate stages2,3 or supporting the cir- toms.
    [Show full text]
  • The Evolution of Heart Failure with Reduced Ejection Fraction Pharmacotherapy: What Do We Have and Where Are We Going?
    Pharmacology & Therapeutics 178 (2017) 67–82 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Associate editor: M. Curtis The evolution of heart failure with reduced ejection fraction pharmacotherapy: What do we have and where are we going? Ahmed Selim, Ronald Zolty, Yiannis S. Chatzizisis ⁎ Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA article info abstract Available online 21 March 2017 Cardiovascular diseases represent a leading cause of mortality and increased healthcare expenditure worldwide. Heart failure, which simply describes an inability of the heart to meet the body's needs, is the end point for many Keywords: other cardiovascular conditions. The last three decades have witnessed significant efforts aiming at the discovery Heart failure of treatments to improve the survival and quality of life of patients with heart failure; many were successful, Reduced ejection fraction while others failed. Given that most of the successes in treating heart failure were achieved in patients with re- Pharmacotherapy duced left ventricular ejection fraction (HFrEF), we constructed this review to look at the recent evolution of Novel drugs HFrEF pharmacotherapy. We also explore some of the ongoing clinical trials for new drugs, and investigate poten- tial treatment targets and pathways that might play a role in treating HFrEF in the future. © 2017 Elsevier Inc. All rights reserved. Contents 1. Introduction..............................................
    [Show full text]
  • Investigations Into the Role of Nitric Oxide in Disease
    INVESTIGATIONS INTO THE ROLE OF NITRIC OXIDE IN CARDIOVASCULAR DEVXLOPMENT DISEASE: INSIGHTS GAINED FROM GENETICALLY ENGINEERED MOUSE MODELS OF HUMAN DISEASE Tony Lee A thesis submitted in conformity with the requirements for the degree of Master's of Science Institute of Medicai Science University of Toronto @ Copyright by Tony C. Lee (2000) National Library Bibliothèque nationale I*I of Canada du Canada Acquisitions and Acquisitions et Bibliogaphic Services services bibliogaphiques 395 Wellington Street 395, rue Wellington Ottawa ON K1A ON4 Ottawa ON KIA ON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distribuer ou copies of this thesis in microfonn, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or othewise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. INVESTIGATIONS INTO THE ROLE OF MTNC OXIDE IN CARDIOVASCULAR DEVELOPMENT AND DISEASE: INSIGHTS GAiNED FROM GENETICALLY ENGINEERED MOUSE MODELS OF HUMAN DISEASE B y Tony Lee A thesis submitted in conformity with the requirements for the degree of Master's of Science (2000) Instinite of Medical Science, University of Toronto In the first expenmental series, the antiatherosclerotic effects of Enalûpril vrrsus Irbesartan were compared in the LDL-R knockout mouse model.
    [Show full text]
  • Hair Growth Stimulation with Nitroxide and Other Radicals
    Europaisches Patentamt 263 European Patent Office © Publication number: 0 327 Office europeen des brevets A1 © EUROPEAN PATENT APPLICATION © Application number: 89300785.6 © Int. CI.4: A61 K 7/06 , A61K 47/00 © Date of filing: 27.01.89 © Priority: 29.01.88 US 149720 © Applicant: PROCTOR, Peter H. Twelve Oaks Medical Tower 4125 Southwest © Date of publication of application: Freeway 09.08.89 Bulletin 89/32 Suite 1616 Houston, TX 77027(US) © Designated Contracting States: © Inventor: PROCTOR, Peter H. AT BE CH OE ES FR GB GR IT Li LU NL SE Twelve Oaks Medical Tower 4125 Southwest Freeway Suite 1616 Houston, TX 77027(US) © Representative: Gore, Peter Manson et al W.P. THOMPSON & CO. Coopers Building Church Street Liverpool L1 3AB(GB) © Hair growth stimulation with nitroxide and other radicals. © Hair growth stimulation with nitroxide and other radicals. A nitroxide radical source compound is applied topically with an adjuvant selected from reducing agents, hydroxyl radical scavengers and antioxidants to activate formation of the nitroxide radical and/or to protect the nitroxide radical from reaction with other free radicals. Also disclosed is a kit for preparing a unit dose for topical application of a nitric oxide generating compound and a reducing agent reactive therewith to form nitric oxide on or in the skin. Other adjuvants include SOD and antiandrogens. Various other radical-forming hair growth stimulants and preparations thereof are disclosed. < w CO CM IN CM CO © Q. Ill Xerox Copy Centre EP 0 327 263 A1 rIAIR GROWTH STIMULATION WITH NITROXIDE AND OTHER RADICALS This invention relates to a composition and method for stimulating hair growth, and to a kit for preparation of such a composition.
    [Show full text]
  • 682.Full.Pdf
    Endogenous and nitrovasodilator-induced release of NO in the airways of end-stage cystic fibrosis patients To the Editors: blood pressure changes recorded, as described previously [8] and in the online supplementary material. A variety of isoforms of nitric oxide (NO) synthases are constitutively expressed in human airway and vascular Nearly undetectable levels of NO were found in CF patients endothelial cells continuously generating NO. NO plays an representing an output of 7.6¡6 ppb over 30 s. This is in important role in regulating lung function in health and contrast to patients presented for routine open heart surgery disease including modulation of pulmonary vascular resis- (91.4¡21 ppb over 30 s; fig. 1). Representative traces are tance, airway calibre and host defence. Production of NO and shown in figure 1A and C of the online supplementary its consumption by fluid-phase reactions can be detected and material. monitored in the exhaled air, providing an important window There was a significant increase in gas-phase NO above baseline to assess the dynamics of NO metabolism in health and levels by 250 mg GTN boluses in CF patients (36.7¡6ppb), inflammatory lung conditions, asthma in particular [1]. which was comparable to that seen in control patients with A series of milestone studies uncovered a relative deficiency of routine open heart surgery (48.7¡4 ppb; fig. 1). Representative pulmonary NO availability in cystic fibrosis (CF), a severe traces of GTN-induced exhaled NO are presented in figure 1B chronic inflammatory lung disease with studies generally and D of the online supplementary material.
    [Show full text]
  • Management of Preoperative Hypertension
    PRINTER-FRIENDLY VERSION AVAILABLE AT ANESTHESIOLOGYNEWS.COM Management of Preoperative Hypertension All rights reserved. Reproduction in whole or in part without permission is prohibited. PETER J. PAPADAKOS, MD, FCCM, FAARC Copyright © 2015 McMahon PublishingDirector Groupof Critical unless Care Medicine otherwise noted. University of Rochester Medical Center School of Medicine and Dentistry Rochester, New York Editorial Advisory Board Member Anesthesiology News KEITH M. FRANKLIN, MD Department of Anesthesiology University of Rochester Medical Center School of Medicine and Dentistry Rochester, New York The authors reported no relevant financial disclosures. ystemic hypertension is an extremely common diagnosis in Sthe US surgical population, with approximately 30% of Americans having the condition. Published studies have shown that the incidence of Management Guidelines hypertension in preoperative patients ranges from 10% The Eighth Joint National Committee (JNC 8) panel to 25%.1 The main risk for preoperative hypertension is released the current Guidelines for Management of High intraoperative hemodynamic instability; both hyper- Blood Pressure in Adults in 2014.3 It is notable that, in tension and hypotension are significantly more com- contrast to JNC 7, these guidelines do not define pre- mon in patients who present as hypertensive.2 Patients hypertension and hypertension, nor do they subdivide who experience instability may go on to develop fur- hypertension into stages based on severity. The new ther sequelae such as stroke and myocardial ischemia. guidelines are more practical in nature and focus on The onset of end-organ damage and the urgency of outlining a set of parameters for initiation and goals of the case are important factors when deciding whether treatment.
    [Show full text]
  • Pharmacological Manipulation of Cgmp and NO/Cgmp in CNS Drug Discovery T
    Nitric Oxide 82 (2019) 59–74 Contents lists available at ScienceDirect Nitric Oxide journal homepage: www.elsevier.com/locate/yniox Review Pharmacological manipulation of cGMP and NO/cGMP in CNS drug discovery T ∗ Michael A. Hollas, Manel Ben Aissa, Sue H. Lee, Jesse M. Gordon-Blake, Gregory R.J. Thatcher Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, USA ARTICLE INFO ABSTRACT Keywords: The development of small molecule modulators of NO/cGMP signaling for use in the CNS has lagged far behind Neurodegeneration the use of such clinical agents in the periphery, despite the central role played by NO/cGMP in learning and cGMP memory, and the substantial evidence that this signaling pathway is perturbed in neurodegenerative disorders, Nitric oxide including Alzheimer's disease. The NO-chimeras, NMZ and Nitrosynapsin, have yielded beneficial and disease- NMDA receptor modifying responses in multiple preclinical animal models, acting on GABA and NMDA receptors, respectively, GABA receptor A providing additional mechanisms of action relevant to synaptic and neuronal dysfunction. Several inhibitors of Migraine fi Alzheimer's disease cGMP-speci c phosphodiesterases (PDE) have replicated some of the actions of these NO-chimeras in the CNS. There is no evidence that nitrate tolerance is a phenomenon relevant to the CNS actions of NO-chimeras, and studies on nitroglycerin in the periphery continue to challenge the dogma of nitrate tolerance mechanisms. Hybrid nitrates have shown much promise in the periphery and CNS, but to date only one treatment has received FDA approval, for glaucoma. The potential for allosteric modulation of soluble guanylate cyclase (sGC) in brain disorders has not yet been fully explored nor exploited; whereas multiple applications of PDE inhibitors have been explored and many have stalled in clinical trials.
    [Show full text]
  • Effects of Oxidative Stress on the Expression and Function of L
    Regulation of the Inducible L-arginine-Nitric Oxide Pathway by Oxidative Stress and Statins M A B de V N Costa PhD 2009 Regulation of the Inducible L-arginine-Nitric Oxide Pathway by Oxidative Stress and Statins Maria Alexandra Barata de Vasconcelos Nunes Costa Submitted to the University of Hertfordshire in partial fulfilment of the requirements of the degree of PhD June 2009 Abstract Oxidative stress (OS) plays a critical role in the pathogenesis of atherosclerosis potentially through interaction with nitric oxide (NO) generated by the inducible nitric oxide synthase (iNOS) pathway. Although considerable literature supports a pro-atherogenic role for iNOS-induced NO, recent evidence suggest an anti-atherogenic property for this enzyme where iNOS-induced NO attenuates atherosclerotic lesions after immune injury, enhancing endothelial integrity, survival, protecting against OS-induced apoptosis and necrosis. We therefore hypothesize that iNOS may have a cardio-protective role in the atherosclerotic vessel and that under conditions of OS, expression and function of this enzyme may be impaired, thus contributing to the deleterious consequences of OS. Experiments have therefore been conducted to establish whether pro-oxidants regulate iNOS expression/function in rat cultured aortic smooth muscle cells (RASMCs). These cells were induced for 24 hours with LPS and IFN-γ to mimic inflammatory conditions. Oxidative stress inducers may modulate iNOS-induced NO production through alteration of the expression and/or function of the inducible L-arginine-NO pathway. We examined the effects of hydrogen peroxide (H2O2), antimycin A and diethyl maleate (DEM) on this pathway in vascular smooth muscle cells. H2O2 had little effect on NO production or L-arginine transport while antimycin A and DEM independently caused a concentration dependent inhibition of both processes.
    [Show full text]
  • Endothelial Dysfunction and Coronary Artery Disease
    Arq Bras Cardiol Caramori Updateand Zago volume 75, (nº 2), 2000 Endothelial dysfunction and coronary artery disease Endothelial Dysfunction and Coronary Artery Disease Paulo R. A. Caramori, Alcides J. Zago Porto Alegre, RS - Brazil For several decades, the vascular endothelium was smooth muscle cells. In contrast, endothelial dysfunction ap- considered a unicellular layer acting as a semipermeable pears to play a pathogenic role in the initial development of membrane between the blood and the interstitium. Recently, atherosclerosis 7-9 and of unstable coronary syndromes 10, it has been demonstrated that the endothelium performs a being associated with atherosclerotic disease risk factors 11-18, large range of important biological functions, participating and being present even before vascular involvement be- in several metabolic and regulatory pathways. Along with comes evident 6,19-21. long-known specialized functions like gaseous exchange in Recent clinical studies have demonstrated that some the pulmonary circulation and phagocytosis in the hepatic drugs well known to reduce the incidence of cardiovascular and splenic circulation, the vascular endothelium performs events, improve endothelial function 22-25. On the other universal roles in the circulation that include participation in hand, clinical interventions like the continuous administra- thrombosis and thrombolytic control, vascular growth, tion of organic nitrates and percutaneous coronary inter- platelet and leukocyte interactions with the vascular wall, ventions may be associated with adverse effects on the and vasomotor tone. vascular endothelium. In the present article, we will discuss The study of endothelium-dependent vasomotor vascular endothelial function versus dysfunction, and reactivity has produced over the years, scientific evidence their impact on cardiovascular disease, in particular atheros- fundamental for the understanding of the endothelium’s clerosis.
    [Show full text]
  • Diagnosis and Management of Acute Heart Failure
    860 Consensus Report Diagnosis and management of acute heart failure Dilek Ural, Yüksel Çavuşoğlu1, Mehmet Eren2, Kurtuluş Karaüzüm, Ahmet Temizhan3, Mehmet Birhan Yılmaz4, Mehdi Zoghi5, Kumudha Ramassubu6, Biykem Bozkurt6 Department of Cardiology, Medical Faculty of Kocaeli University; Kocaeli-Turkey; 1Department of Cardiology, Medical Faculty of Eskişehir Osmangazi University; Eskişehir-Turkey; 2Department of Cardiology, Siyami Ersek Hospital; İstanbul-Turkey; 3Department of Cardiology, Turkey Yüksek İhtisas Hospital; Ankara-Turkey; 4Department of Cardiology, Medical Faculty of Cumhuriyet University; Sivas-Turkey; 5Department of Cardiology, Medical Faculty of Ege University; İzmir-Turkey 6Department of Cardiology, Baylor College of Medicine and University of Texas Medical School; Texas-USA ABSTRACT Acute heart failure (AHF) is a life threatening clinical syndrome with a progressively increasing incidence in general population. Turkey is a country with a high cardiovascular mortality and recent national statistics show that the population structure has turned to an 'aged' population. As a consequence, AHF has become one of the main reasons of admission to cardiology clinics. This consensus report summarizes clinical and prognostic classification of AHF, its worldwide and national epidemiology, diagnostic work-up, principles of approach in emergency department, intensive care unit and ward, treatment in different clinical scenarios and approach in special conditions and how to plan hospital discharge. (Anatol J Cardiol 2015: 15; 860-89) Keywords: acute heart failure, diagnosis, management 1. Introduction of Academic Emergency Medicine (5) do also take attention of cardiologists. However, Turkish AHF patients show some epide- Acute heart failure (AHF) is defined as a life threatening clini- miological differences than European or American AHF patients cal syndrome with rapidly developing or worsening typical heart and some pharmacological (e.g.
    [Show full text]