Myocardial protection 2004


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Myocardial protection 2004

  1. 1. Myocardial Protection
  2. 2. This book is dedicated to our wivesMichelle Ricci andHelen Salerno
  3. 3. MyocardialTProtectionEDITED BYTomas A. Salerno, MDProfessor and ChiefDivision of Cardiothoracic SurgeryUniversity of MiamiJackson Memorial HospitalMiami, FloridaandMarco Ricci, MDAssistant Professor of SurgeryDivision of Cardiothoracic SurgeryStaff Surgeon, Section of Pediatric Cardiac SurgeryUniversity of MiamiJackson Memorial HospitalMiami, FloridaBlackwellPublishingFutura, an imprint of Blackwell Publishing
  4. 4. © 2004 by Futura, an imprint of Blackwell PublishingBlackwell Publishing, Inc./Futura Division, 3 West Main Street, Elmsford, New York 10523, USABlackwell Publishing, Inc., 350 Main Street, Maiden, Massachusetts 02148-5020, USABlackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UKBlackwell Science Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, AustraliaAll rights reserved. No part of this publication may be reproduced in any form or by anyelectronic or mechanical means, including information storage and retrieval systems, withoutpermission in writing from the publisher, except by a reviewer who may quote brief passages ina review.0304050654321ISBN: 1-4051-1643-9Library of Congress Cataloging-in-Publication DataMyocardial protection / edited by Tomas A. Salerno and Marco Ricci. — Isted. p.; cm. Includes bibliographical references and index. ISBN 1-4051-1643-9 1. Heart—Surgery—Complications—Prevention. 2. Myocardium. 3. Cardiac arrest, Induced. 4. Myocardial reperfusion. 5. Re-perfusion injury—Prevention. I. Salerno, Tomas A. II. Ricci, Marco, M.D. [DNLM: 1. Cardiovascular Surgical Procedures—methods. WG168M99582004] RD598.M9152004 617.4l-dc21 2003009294A catalogue record for this title is available from the British LibraryAcquisitions: Steven KornProduction: Julie ElliottTypesetter: Graphicraft Ltd, Hong KongPrinted and bound in Great Britain by CPI Bath, BathFor further information on Blackwell Publishing, visit our website:www.futuraco.comwww.blackwellpublishing.comNotice: The indications and dosages of all drugs in this book have been recommended in themedical literature and conform to the practices of the general community. The medicationsdescribed do not necessarily have specific approval by the Food and Drug Administration foruse in the diseases and dosages for which they are recommended. The package insert for eachdrug should be consulted for use and dosage as approved by the FDA. Because standards forusage change, it is advisable to keep abreast of revised recommendations, particularly thoseconcerning new drugs.
  5. 5. ContentsList of Contributors, vii 9 Intermittent Antegrade Warm Blood Cardioplegia, 75Foreword, xi Antonio Maria Calafiore, MD, Giuseppe Vitolla,W. Gerard Rainer, MD MD, and Angela laco, MDPreface, xii 10 Antegrade, Retrograde, or Both?, 82 1 The History of Myocardial Protection, 1 Frank G. Scholl, MD and Davis C. Drinkwater, MD Anthony L Panos, MD, MSc, FRCSC, FACS 11 Miniplegia: Biological Basis, Surgical Techniques, 2 The Duality of Cardiac Surgery: Mechanical and and Clinical Results, 88 Metabolic Objective, 13 Giuseppe DAncona, MD, Hratch Karamanoukian, Gerald D. Buckberg, MD MD, LuigiMartinelli, MD, Michael O. Sigler, MD, and TomasA. Salerno, MD 3 Modification of Ischemia-Reperfusion-Induced Injury by Cardioprotective Interventions, 18 12 Substrate Enhancement in Cardioplegia, 94 Ming Zhang, MD, Tamer Sallam, BS, BA, Yan-Jun Shafie Fazel, MD, Marc P. Pelletier, MD, and Xu, PhD, andNaranjan S. Dhalla, PhD, MD Bernard S. Goldman, MD (Hon), DSc (Hon) 13 Is There a Place for On-Pump, Beating Heart 4 Anesthetic Preconditioning: A New Horizon in Coronary Artery Bypass Grafting Surgery? The Myocardial Protection, 33 Pros and Cons, 119 Nader D. Nader, MD, PhD, FCCP Simon Fortier, MD, Roland G. Demaria, MD, 5 Myocardial Protection During Acute Myocardial PhD, FETCS, and Louis P. Perrault, MD, PhD, Infarction and Angioplasty, 43 FRCSC, FACS Alexandre C. Ferreira, MD, FACC and Eduardo 14 Myocardial Protection in Beating Heart Coronary deMarchena, MD, FACC Artery Surgery, 126 6 Intermittent Aortic Cross-Clamping for Vinod H. Thourani, MD and John D. Puskas, Myocardial Protection, 53 MD, MSc Fabio Biscegli Jatene, MD, PhD, Paulo M. 15 Beating Heart Coronary Artery Bypass Grafting: Pego-Fernandes, MD, PhD, and Alexandre Intraoperative Strategies to Avoid Myocardial Ciappina Hueb, MD Ischemia, 134 7 Intermittent Warm Blood Cardioplegia: The Kushagra Katariya, MD, Michael O. Sigler, MD Biochemical Background, 59 and Tomas A. Salerno, MD Ganghong Tian, MD, PhD, TomasA. Salerno, MD, 16 Beating Heart Coronary Artery Bypass in Patients and Roxanne Deslauriers, PhD with Acute Myocardial Infarction: A New Strategy 8 Warm Heart Surgery, 70 to Protect the Myocardium, 144 Hassan Tehrani, MB, BCh, Atiq Rehman, MD, Jan F. Gummert, MD, PhD, Michael A. Borger, Pierluca Lombardi, MD, Mohan Thanikachalam, MD, PhD, Ardawan Rastan, MD, and Friedrich W. MD, and Tomas Salerno, MD Mohr, MD, PhD
  6. 6. VI Contents17 Beating Heart Coronary Artery Bypass with 27 Myocardial Preconditioning in the Experimental Continuous Perfusion Through the Coronary Model: A New Strategy to Improve Myocardial Sinus, 152 Protection, 230 Harinder Singh Bedi, MCh, FIACS Eliot R. Rosenkranz, MD, Jun Feng, MD, PhD, and Hong-Ling Li, MD, MSc18 On-Pump Beating Heart Surgery for Dilated Cardiomyopathy and Myocardial Protection, 160 28 New Concepts in Myocardial Protection in Tadashi Isomura, MD and Hisayoshi Suma, MD Pediatric Cardiac Surgery, 264 Bindu Bittira, MD, MSc, Dominique Shum-Tim,19 Myocardial Protection with Beta-Blockers in MD, MSc, and Christo I. Tchervenkov, MD Valvular Surgery, 167 Nawwar Al Attar, FRCS, MSc, FETCS, Marcio 29 Extracardiac Fontan: The Importance of Avoiding Scorsin, MD, PhD, andArrigo Lessana, MD, FETCS Cardioplegic Arrest, 275 Carlo F. Marcelletti, MD and Raul F. Abella,20 Myocardial Protection in Minimally Invasive MD Valvular Surgery, 174 Rene Pretre, MD and Marko I. Turina, MD 30 Preservative Cardioplegic Solutions in Cardiac Transplantation: Recent Advances, 28221 Intermittent Warm Blood Cardioplegia in Aortic Romualdo J. Segurola Jr., MD and Rosemary F. Valve Surgery: An Update, 181 Kelly, MD M. Saadah Suleiman, PhD, Raimondo Ascione, MD, and Gianni D. Angelini, MD, FRCS 31 Myocardial Preservation in Clinical Cardiac Transplantation: An Update, 29222 Myocardial Protection in Surgery of the Louis B. Louis IV, MD, Xiao-Shi Qi, MD, PhD, Aortic Root, 189 and Si M. Pham, MD, FACS Stephen Westaby, PhD, MS, FETCS 32 Myocardial Protection During Left Ventricular23 Myocardial Protection in Major Aortic Assist Device Implantation, 301 Surgery, 193 Aftab R. Kherani, MD, Mehmet C. Oz, MD, and Marc A. Schepens, MD, PhD and Andrea Nocchi, YoshifumiNaka, MD, PhD MD 33 Gene Therapy for Myocardial Protection, 30424 Recent Advances in Myocardial Protection for Said F. Yassin, MD and Christopher G. McGregor, Coronary Reoperations, 196 MD Jan T. Christenson, MA, MD, PhD, PD, FETCS and Afksendiyos Kalangos, MD, PhD, PD, FETCS 34 Aortic and Mitral Valve Surgery on the Beating Heart, 31125 Myocardial Protection During Minimally Invasive Marco Ricci, MD, Pierluca Lombardi, MD, Michael Cardiac Surgery, 203 O. Sigler, MD, Giuseppe DAncona, MD and Saqib Masroor, MD, MHS and Kushagra Katariya, TomasA. Salerno, MD MD Index, 32126 Current Concepts in Pediatric Myocardial Protection, 207 Bradley S. Allen, MD
  7. 7. List of ContributorsRaul F. Abel la, MD Jan T. Christenson, MA, MD, PHD,Consultant in Cardiac Surgery, Division of Pediatric PD, FETCSCardiovascular Surgery, Ospedale Civico di Palermo, Chief of Clinic, Department of Surgery, Clinic forPalermo, Sicily, Italy Cardiovascular Surgery, University Hospital of Geneva, Geneva, SwitzerlandNawwar Al Attar, FRCS,MSc, FETCS Giuseppe DAncona, MDCardiac Surgeon, Department of Cardiac Surgery, Hospital San Martino Geneva, University of GenevaCentre Cardiologique du Nord, St. Denis, France Medical School, Geneva, ItalyBradley S. Allen, MD Eduardo deMarchena, MD, FACC Professor of Medicine and Surgery, Chief, InterventionalChief, Division of Pediatric Cardiac Surgery, University of Cardiology, University of Miami School of Medicine,Texas, Houston; Memorial Hermann Childrens Hospital, Miami, FL, USAHouston Texas, USA Roland G. Demaria, MD, PHD, FETCSGianni D. Angelini, MD, FRCS Department of Surgery and Research Center, MontrealBristol Heart Institute, University of Bristol, Bristol, Heart Institute, Montreal, Quebec, CanadaUnited Kingdom Roxanne Deslauriers, PHDRaimondo Ascione, MD Director of Research, Institute for Biodiagnostics, NationalBristol Heart Institute, University of Bristol, Bristol, Research Council, Winnipeg, Manitoba, CanadaUnited Kingdom Naranjan S. Dhalla, PHD, MD(Hon),Harinder Singh Bedi, MCH, FIACS DSc (Hon)Chief Cardiac Surgeon and Chairman, Cardiovascular Distinguished Professor and Director, Institute ofSurgery, Metro Heart Institute, Noida, New Delhi, India Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, CanadaBindu Bittira, MD, MSCChief Resident, Thoracic Surgery, Division of Davis C. Drinkwater, MDCardiothoracic Surgery, The Montreal General Hospital, Department of Cardiothoracic Surgery, VanderbiltMcGill University, Montreal, Quebec, Canada University Medical Center, Nashville, TN, USAMichael A. Borger, MD, PHD Shaf ie Fazel, MDLeipzig Heart Center, University of Leipzig, Leipzig, Resident, Division of Cardiac Surgery, University ofGermany Toronto, Toronto, Ontario, CanadaGerald D. Buckberg, MD Alexandre C. Ferreira, MD, FACCDivision of Thoracic and Cardiovascular Surgery, Assistant Professor of Medicine, Coordinator,University of California, Los Angeles, Los Angeles, Interventional Training Program, University of MiamiCA, USA School of Medicine, Miami, FLAntonio Maria Calaf iore, MD Simon Fortier, MDProfessor and Chief, Department of Cardiac Surgery, Department of Surgery and Research Center, Montreal"G. DAnnunzio" Chieti University, Chieti, Italy Heart Institute, Montreal, Quebec, Canada VII
  8. 8. VIM List of ContributorsBernard S. Goldman, MD Pierluca Lombard!, MDSurgeon, Division of Cardiovascular Surgery, Sunnybrook Fellow in Cardiothoracic Surgery, Division ofand Womens College Health Sciences Centre, Toronto; Cardiothoracic Surgery, Daughtry Family Department ofProfessor, Department of Surgery, University of Toronto, Surgery, University of Miami, Miami, FL, USAToronto, Ontario, Canada; Editor-in-Chief, Journal ofCardiac Surgery Louis B. Louis IV, MD Division of Cardiothoracic Surgery, University of MiamiJan F. Gummert, MD, PHD School of Medicine, Miami, FL, USALeipzig Heart Center, University of Leipzig, Leipzig,Germany Carlo F. Marcel letti, MD Cardiovascular Surgeon-in-Chief, Division of Pediatric Cardiovascular Surgery, Ospedale Civico di Palermo,Alexandre Ciappina Hueb, MDDepartment of Thoracic and Cardiovascular Surgery, Palermo, Sicily, ItalyHeart Institute, University of Sao Paulo, Sao Paulo,Brazil Luigi Martinelli, MD Hospital San Martino Genova, University of Geneva Medical School, Genova, ItalyAngela lacd, MDStaff Surgeon, Department of Cardiac Surgery, "G.DAnnunzio" Chieti University, Chieti, Italy Saqib Masroor, MD, MHS Division of Thoracic and Cardiovascular Surgery, University of Miami, Jackson Memorial Hospital, Miami, FL, USATadashi Isomura, MDDirector, Cardiovascular Surgery, Hayama Heart Center,Hayama, Kanagawa, Japan Christopher G. McGregor, MD Mayo Clinic Foundation, Rochester, MN, USAFabio Biscegli Jatene, MD, PHD Friedrich W. Mohr, MD, PHDDepartment of Thoracic and Cardiovascular Surgery, Leipzig Heart Center, University of Leipzig, Leipzig,Heart Institute, University of Sao Paulo, Sao Paulo, Brazil GermanyAf ksendiyos Kalangos, MD, PHD, Nader D. Nader, MD, PHD, FCCPPD, FETCS Associate Professor of Anesthesiology, Surgery, Pathology,Chief of Service, Department of Surgery, Clinic for and Anatomical Sciences, State University of New York atCardiovascular Surgery, University Hospital of Geneva, Buffalo; Chief, Perioperative Care and Anesthesia, UpstateGeneva, Switzerland VA Healthcare System, Buffalo, NY, USAHratch Karamanoukian, MD Yoshifumi Naka, MD, PHDCenter for Less Invasive and Robotic Heart Surgery, Kaleida Herbert Irving Assistant Professor of Surgery, Director,Health, Buffalo, NY, USA Mechanical Circulatory Support, Columbia University, College of Physicians and Surgeons, New York, NY, USAKushagra Katariya, MD Andrea Nocchi, MDDivision of Cardiothoracic Surgery, University of Miami, Cardiothoracic Surgeon, Department of Cardiac Surgery,Jackson Memorial Hospital, Miami, FL, USA Ospedale Carlo Poma, Mantova, ItalyRosemary F. Kelly, MD Mehmet C. Oz, MDAssistant Professor of Surgery, University of Minnesota, Associate Professor of Surgery, Director, The CardiovascularCardiovascular and Thoracic Surgery, Minneapolis, MN, Institute, Columbia University, College of Physicians andUSA Surgeons, New York, NY, USAAftab R. Kherani, MD Anthony L. Panos, MD, MSC, FRCSC,Resident in General Surgery, Duke University Medical FACSCenter, Durham, NC; Research Fellow, Division of Division of Cardiothoracic Surgery, William S. MiddletonCardiothoracic Surgery, Columbia University, College of VA Medical Center; Associate Professor, University ofPhysicians and Surgeons, New York, NY, USA Wisconsin at Madison, Madison, WI, USAArrigo Lessana, MD, FETCS Paulo M. Pego-Fernandes, MD, PHDChief of Surgery, Department of Cardiac Surgery, Centre Department of Thoracic and Cardiovascular Surgery, HeartCardiologique du Nord, St. Denis, France Institute, University of Sao Paulo, Sao Paulo, Brazil
  9. 9. List of Contributors IXMarc P. Pel letter, MD Tamer Sal lam, BS, BASurgeon, Division of Cardiovascular Surgery, Sunnybrook Research Fellow, Institute of Cardiovascular Sciences, St.and Womens College Health Sciences Centre, Toronto; Boniface General Hospital Research Centre, Winnipeg,Assistant Professor, Department of Surgery, University of Manitoba, CanadaToronto, Toronto, Ontario, Canada Marc A. Schepens, MD, PHDLouis P. Perrault, MD, PHD, FRCSC, FACS Department of Cardiothoracic Surgery, St. AntoniusDepartment of Surgery and Research Center, Montreal Hospital, Nieuwegein, The NetherlandsHeart Institute, Montreal, Quebec, Canada Frank G. Scholl, MD Department of Cardiothoracic Surgery, VanderbiltSi M. Pham, MD, FACS University Medical Center, Nashville, TN, USADirector, Section of Cardiopulmonary Transplantation,Division of Cardiothoracic Surgery, University of MiamiSchool of Medicine, Miami, FL Marcio Scorsin, MD, PHD Cardiac Surgeon, Department of Cardiac Surgery, Centre Cardiologique du Nord, St. Denis, FranceRene Pretre, MDCardiovascular Surgery, University Hospital Zurich, Zurich,Switzerland Romualdo J. Segurola Jr., MD Cardiovascular and Thoracic Surgery, University of Minnesota, Minneapolis, MN, USAJohn D. Puskas, MD, MSCAssociate Professor of Surgery, Carlyle Fraser Heart Center, Michael O. Sigler, MDDivision of Cardiothoracic Surgery, Department of Surgery, Department of Surgery, University of Miami, JacksonEmory University School of Medicine, Atlanta, GA, USA Memorial Hospital, Miami, FL, USAXiao-Shi Qi, MD, PHD Dominique Shum-Tim, MD, MSCDivision of Cardiothoracic Surgery, University of Miami Staff Surgeon, The Montreal Childrens Hospital; StaffSchool of Medicine, Miami, FL, USA Surgeon, The Montreal General Hospital; Assistant Professor of Surgery, McGill University, Montreal, Quebec,W. Gerard Rainer, MD CanadaDistinguished Clinical Professor of Surgery, University ofColorado Health Sciences Center; Past President and M. Saadah Suleiman, PHDHistorian, Society of Thoracic Surgeons Bristol Heart Institute, University of Bristol, Bristol, United KingdomArdawan Rastan, MDLeipzig Heart Center, University of Leipzig, Leipzig, Hisayoshi Suma, MDGermany Honored Director, Cardiovascular Surgery, Hayama Heart Center, Hayama, Kanagawa, JapanAtiq Rehman, MDFellow in Cardiothoracic Surgery, Division of Christo I. Tchervenkov, MDCardiothoracic Surgery, Daughtry Family Department of Director, Cardiovascular Surgery, The Montreal ChildrensSurgery, University of Miami, Miami, FL, USA Hospital, Montreal, Quebec, CanadaMarco Ricci, MD Hassan Tehrani, MB, BCH Fellow in Cardiothoracic Surgery, Division ofAssistant Professor of Surgery, Division of Cardiothoracic Cardiothoracic Surgery, Daughtry Family Department ofSurgery, University of Miami, Jackson Memorial Hospital, Surgery, University of Miami, Miami, FL, USAMiami, FL, USA Mohan Thanikachalam, MDEliot R. Rosenkranz, MD Fellow in Cardiothoracic Surgery, Division ofDirector, Section of Pediatric Cardiac Surgery, Associate Cardiothoracic Surgery, Daughtry Family Department ofProfessor of Surgery, University of Miami, Jackson Surgery, University of Miami, Miami, FL, USAMemorial Hospital, Miami, FL, USA Vinod H. Thourani, MDTomas A. Salerno, MD Resident in Cardiothoracic Surgery, Carlyle Fraser HeartProfessor and Chief, Division of Cardiothoracic Surgery Center, Division of Cardiothoracic Surgery, Department ofUniversity of Miami, Jackson Memorial Hospital, Surgery, Emory University School of Medicine, Atlanta, GA,Miami, FL, USA USA
  10. 10. List of ContributorsGanghong Tian, MD, PHD Yan-Jun Xu, PHDAssociate Research Officer, Institute for Biodiagnostics, Research Scientist, Institute of Cardiovascular Sciences, St.National Research Council, Winnipeg, Manitoba, Canada Boniface General Hospital Research Centre, Winnipeg, Manitoba, CanadaMarko I. Turina, MDCardiovascular Surgery, University Hospital Zurich, Zurich, Said F. Yassin, MDSwitzerland Division of Cardiothoracic Surgery, University of Miami School of Medicine, Miami, FL, USAGiuseppe Vitolla, MDStaff Surgeon, Department of Cardiac Surgery, Ming Zhang, MD"G. DAnnunzio" Chieti University, Chieti, Italy Research Fellow, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg,Stephen Westaby, PHD, MS, FETCS Manitoba, CanadaOxford Heart Centre, John Radcliffe Hospital, Oxford,United Kingdom
  11. 11. ForewordWhen open heart surgery became a possibility one- Salerno and Ricci have admirably filled a neededhalf century ago, it seems that considerable atten- niche by pulling together various approaches andtion was directed toward protection of the body as a modalities for myocardial protection applicable towhole (perhaps it was assumed that this would take many different scenarios—the chapter titles speak forcare of the needs of the heart as well). Hypothermia, themselves in exhibiting the array of situations dis-partial perfusion, intermittent aortic cross-clamping cussed in detail along with au courant data regardingand a variety of other techniques were thought to various methods of protection based upon pioneer-suffice until careful observers noted occurrence of ing investigations by contributors such as Kirklin,such events as "stone heart," subendocardial ischemia, Buckberg, and others.and other manifestations of inadequate myocardial This volume is an absolute necessity for cardiac sur-protection. This dramatically demonstrated that the geons in training and in practice and is so designed toheart could not be treated as just any other organ or be an invaluable teaching tool and reference into thepart of the body. Its function is so different because of foreseeable future.its intricate neuromuscular structure that investiga- W. Gerard Rainer, MDtions were begun (and continue until the present) to Distinguished Clinical Professor of Surgerydefine the cellular metabolic needs of the heart and to University of Colorado Health Sciences Centerdevelop ways to meet those needs so that, hopefully, Past President and Historian, Societyminimal cardiac function will be lost following correc- of Thoracic Surgeonstion of the underlying abnormality. XI
  12. 12. PrefaceCardiac surgery has undergone major changes in the need to put together a collection of manuscripts writ-recent past. With changes came new knowledge, tech- ten by experts in the different fields of myocardial pro-nology and progress, all aimed at providing better tection. The idea is to give the reader an up-to-datecare to our patients. Fundamentally, however, cardiac view of how myocardial protective strategies are beingsurgery "is myocardial protection," the realization utilized by surgeons performing different procedures.that no matter how perfect the reparative surgery, Although it was recognized that the past plays a majormyocardial function has to be preserved for a short role in current methods of myocardial protection, theand long-term successful outcome. The pace of tech- book was intentionally aimed at the present and thenological advancements has accelerated over the last future.five years, allowing surgeons to perform cardiac surgery The editors are grateful to all the authors anddifferently and more comfortably. For each proced- co-authors who wrote this modern book. Their tasksure, there is the need for different technology, such as were time consuming, aside from their daily work asdevices, valves, suture materials, stabilizers, shunts, clinicians and scientists. It is a tribute to them that theblowers, and others. One factor, however, has remained publishers were able to print a textbook that is up toconstant, i.e. the need for individualization for a date with current knowledge regarding myocardialspecific method of myocardial protection tailored to protection.each operation. TomasA. Salerno, MD It is in this spirit that the editors of this book felt the Marco Ricci, MDXII
  13. 13. CHAPTER 1 The history of myocardial protection Anthony L Panos, MD, MSC, FRCSC, FAGS outline of the work that has brought us to where weIntroduction are today.The history of myocardial protection is a rich andvaried story that encompasses the work of basic scient- Early cardiac physiologyists and clinicians working in different countries overmany years. It is an excellent example of clinical prob- The whole of biologic and medical sciences floweredlems stimulating basic research and then translating at the end of the 19th century, as exemplified by thethat knowledge back "from the bench to the bedside." microbiologic discoveries of Pasteur, Kochs postul-Many surgeons are aware of the famous quotation by ates, and Claude Bernards emphasis on homeostasisthe great 19th century surgeon Theodore Billroth, that as a principle, to maintain the "internal milieu" [7]."any surgeon who operates upon the heart, should There were also great advances in physiology, espe-lose the respect of his colleagues." At the time that cially cardiac physiology and the understanding ofBillroth made that statement, cardiac surgery was muscle mechanics by Otto Frank [8-10], and Starlingindeed very hazardous because knowledge and tech- [11].niques were not available to make it safe. The ensuing The pioneering work of Sydney Ringer on theyears saw a growth in knowledge and new technology effects of electrolytes on the regulation of the heartthat led to the development of modern cardiac surgery beat [12-15] is summarized by Toledo-Pereyra [16].as we currently practice it. Physiologists in the late 19th century thought about Myocardial protection was a key part of these control of cardiac function in terms of myogenic ver-developments that allowed safe cardiac surgery to sus neurogenic theories. It was in this atmosphere thatbe performed. The term myocardial protection en- Ringer conducted his elegant experiments and showedcompasses more than just cardioplegia, and can be the effects of various ions on the heartbeat. Ringerssaid to include things such as the perioperative man- work was initally not appreciated in Europe, but wasagement of patients with medical treatment (such followed by American physiologists, who extended itas beta-blockers, etc.), or support devices (such as [17-21]. As early as 1935, Zwikster and Boyd hadintraaortic balloon pumps), better anesthetic agents, shown that the heart could be reversibly arrested usingand better hemodynamic management. All of these potassium [22]. However, surgeons did not appreciatetreatments contribute to making cardiac surgery this physiological research, and the clinical applica-safer, and to get a sick patient through a major opera- tion of this knowledge would occur 20 years later.tion. However, for the purposes of our discussion we Cardiovascular physiology continued to expandwill focus more on the development of cardioplegia. through the early years of the 20th century, but wasThis is a very large field of research and has been carried on largely by zoologists, and physiologistsreviewed in several books [1-5] and review articles working on problems of basic science. For example,[6]. In one chapter we will only be able to go over there were studies of the thebesian vein system thatsome of the important highlights, and give a general would later become especially important to the
  14. 14. CHAPTER 1technique of retrograde cardioplegia [23-31]. Others of mitral valve stenosis [57-59] or pulmonary valvestudied the electrophysiology [21,32] of the heart, stenosis [60]. There were a variety of ingenious opera-the physiology of coronary blood flow [33-38], myo- tions done through artificial "wells," for example, tocardial energetics [31,39-41], and the relationships allow closure of an atrial septal defect "underwater"between coronary blood flow and cardiac mechanics [61].[42-44]. All of this important basic science work was All of these operations reflected the limits of thecrucial to later clinical applications. technology of their time. Most were very ingenious, and in many ways ahead of their time. However, in the final analysis they all required the ability to supportEarly operations—closed the circulation to make the breakthroughs that theySurgeons returned from the second world war after were seeking.exposure to military surgery, and had developed aninterest in the treatment of traumatic chest wounds Early operations—open [45]. This renewed interest in cardiac surgery led to agreat expansion of the specialty in the 1950s. Cardiac Experimental work using inflow occlusion to allowsurgery developed later than other surgical specialties, work within the heart (i.e. "open" operations) foundlargely due to the technical difficulties of operating on that brain injury occurred when the cerebral bloodthe heart. The surgeon could not support the circula- flow was interrupted. The irreversible brain injurytion while working on the heart, and this limited the occurred with interruptions of about 4 min duration.kinds of surgery that could be done upon the heart. As Bigelow first proposed the use of hypothermia dur-a result, the early operations for cardiac disease con- ing cardiac surgery in 1950 [62]. This led Bigelow,sisted mostly of extracardiac procedures, such as the Swan, Boerema, and others to investigate the useligation of a patent ductus arteriosus by Gross and of hypothermia in cardiac surgery [39,62-71]. ThisHubbard [46], and the revolutionary work of Blalock laboratory work was then taken into the clinical worldand Taussig to create palliative shunts for the treat- and the first intracardiac repairs using systemicment of cyanotic congenital heart disease [47]. hypothermia were reported [67,69,70,72]. However, There were other early attempts to operate on it is important to note that in these early papers thethe surface of the heart. These operations included original intention for the use of hypothermia was tomethods to treat ischemic heart disease by increas- protect primarily the brain, and not the the blood flow to the myocardium by creating In 1950 Bigelow found that in experimental modelsnoncoronary collateral blood supply to the heart. the total body oxygen consumption decreased withPericardial adhesions were created, for example, by temperature, and this included myocardial metabol-means of pericardial irritation, or by covering the ism [62,63]. This data was later expanded and becameheart with omentum after epicardial and pericardial the rationale for the use of hypothermia as a techniqueabrasion [48-50]. Some investigators studied the to protect the heart.effects of coronary sinus ligation in animal models The crucial technology of artificial circulatory sup-in an effort to impede venous outflow and thereby port was developed, principally by the perseverance ofimprove coronary artery perfusion of myocardium Dr John Gibbon [73-75]. The "heart-lung machine"[27-29,51]. Dr Claude Beck developed an operation of Gibbon could support the circulation, and thisto "revascularize" the heart using the cardiac venous development really allowed cardiac surgery to be donesystem [48-50]. The Beck operation created a venous [76]. Surgeons could at last safely support the patientsbypass to the epicardial veins of the heart and sub- circulation while working within the heart. However,sequent ligation of the coronary sinus [52-56]. It is in order to provide the bodys oxygen requirements,remarkable how much Beck achieved with the limited high flow rates were needed. This was initially a dif-technology available to him, and how prescient his ficult problem, and stressed the available technologywork was, predicting that surgery would become of early oxygenators. Investigators reassessed Bigelowsimportant in the treatment of angina pectoris. earlier findings for total body oxygen consumption There were also some closed operations performed, and temperature dependence. They found that bysuch as mitral commissurotomy for the treatment adding hypothermia, the total body requirements for
  15. 15. History of myocardial protectionoxygen were greatly decreased in patients. Therefore, found that there was no ultrastructural damagethe total flow rates needed to provide the bodys with the magnesium-procainamide method [96,97].oxygen requirements could also be decreased greatly. Bretschneider also developed the idea of buffering of the cardioplegic solution as an important principle of myocardial protection [92,94]. This continuing workCardioplegia on cardioplegia in Europe was important to the even-The first use of "elective cardiac arrest" was by Melrose tual resurgence of interest in America in the 1955, who also coined the term "cardioplegia" forthe technique [77]. Melrose used a solution con- Reassessment of myocardialtaining potassium to remove the transmembrane damageelectrical potential and hence to stop the cardiac im-pulse and arrest the heart in diastole. However, once In the 1960s surgeons reviewing the complicationsagain, the paper by Melrose makes it clear that his of cardiac surgery did not consider that the complica-initial impetus to devise the technique was to reduce tions were due to the surgery itself. Slowly data accu-the foaming that occurred with the cardiopulmonary mulated that questioned this prevailing concept. Inmachines he was using, in order to reduce air emboli, 1967, Tabers group reported that there was myocar-and not to protect the heart. dial necrosis following cardiac surgery [98]. He found Also, during the 1950s there was the first use of that patchy necrosis affected as much as 30% of thealternate routes of cardioplegia administration and myocardium. In a paper by Najafis group, the authorsvarious temperatures [78-80]. Gott et al. used retro- found that there was subendocardial necrosis seen ingrade perfusion of the heart via the coronary sinus patients who underwent valve surgery, with normalusing warm blood with Melrose solution, both experi- coronary arteries [99]. In the setting of double valvementally and clinically [78,79]. Lilleheis group also operations Cooley et al. first described the conditionused retrograde perfusion of the coronary sinus with of "stone heart" [100]. This was seen when theblood during aortic valve surgery [80]. ischemic time was prolonged, and the hearts went Gradually as experience with the technique increased into a state of ischemic contracture.[81], the long-term effects of Melrose solution became Other investigators also found that patients under-known. Surgeons found that there was late vascular going valve surgery, who had otherwise normal coron-and myocardial injury in these patients [82-88]. As a ary arteries, had perioperative myocardial infarctionresult, surgeons abandoned the technique. [101,102]. Storstein et al. studied the mechanisms Some surgeons used direct ostial cannulation of the of these infarctions [103]. In other studies, patientscoronary ostia in order to perfuse the heart during undergoing atrial septal defect repair had enzymesurgery. However, reports of ostial stenoses discour- evidence of myocardial infarction [104]. This gradu-aged most surgeons from using this technique [89,90]. ally led surgeons to once again question whether the In the late 1950s and early 1960s Shumway intraoperative myocardial protection was effectivelyand Lower reported their work using hypothermic protecting the heart, and whether they could improvemethods to protect the heart [91]. The use of their techniques.hypothermia became widespread, and combined withintermittent ischemia became the dominant method Reintroduction of cardioplegiaof myocardial management during cardiac surgery in Some investigators, such as Tyers, identified thethe USA during the 1960s. Despite the problems with problems with Melrose solution as toxicity due toMelrose solution, some surgeons in Europe continued inappropriately high ionic concentrations, rather thanto use and develop cardioplegia [92]. Bretschneider due to the idea of electromechanical arrest in andand others continued to develop the methods of car- of itself [105,106]. In 1973 Gay and Ebert pioneereddioplegia based on an "intracellular" electrolyte solu- the reintroduction of cardioplegia using crystalloidtion, which reduced transmembrane gradients, and solutions with much lower concentrations of KC1,arrested the heart [93-95]. Others, such as Hoelscher, which were just sufficient to give electromechanicalstudied the effects of magnesium-procainamide arrest [107]. In 1974 Hearses group reported theiras compared to potassium citrate cardioplegia, and experimental work with a potassium chloride solution
  16. 16. CHAPTER 1 [108]. In 1976 another paper extended this work cardioplegia, the so-called terminal "hot-shot," was [109]. These experimental papers led to the develop- confirmed experimentally [128] and clinically [129] toment of cardioplegic solutions for clinical use, such as be advantageous to myocardial metabolism.the St Thomas solution [108-112], which was first Buckbergs group also investigated the use of aminoused clinically in 1976 [ 110]. acids in the cardioplegia to provide substrates for A great deal of work ensued on the various com- Krebs cycle [ 130]. This method of substrate enhance-ponents of cardioplegia solutions, on what should be ment has been shown to be beneficial clinically, reduc-included in the solutions, and in what concentrations. ing the need for inotropic support or the use of theMany papers were written on the proper use and con- intraaortic balloon pump [131-133]. This work alsocentrations of buffers, Mg2+, Ca2+, acid-base balance, led to the development of "secondary" blood cardio-local anesthetics, and even oxygen. plegia to resuscitate poorly functioning injured hearts Some investigators wanted to deliver oxygen during at the end of the operation with a further period ofthe arrest period and introduced oxygen into the car- warm cardioplegic arrest [ 134,135].dioplegia solutions to "oxygenate" them [113,114].There was even interest in the use of artificial solutions Continuous cardioplegiasuch as fluorocarbons for cardioplegia because of theiroxygen-carrying capacity [115-118]. Salernos group at the University of Toronto was interested in myocardial protection, both experiment- ally and clinically. They questioned whether surgeonsBlood cardioplegia could avoid ischemia altogether [136]. Several investi-The interest in delivering oxygen and buffering the gators had used continuous cold blood cardioplegia,cardioplegia solution led investigators to question in patients undergoing valve surgery [137], in acutewhether the best buffer and oxygen-carrying could be postinfarction mitral regurgitation [138], and inachieved by blood itself. Dr Gerald Buckbergs group patients with ventricular hypertrophy [139].working at UCLA did a large amount of experimental The use of continuous blood cardioplegia was donework that led to the development of blood cardio- in an effort to provide oxygen and substrate through-plegia in the late 1970s [119]. Other surgeons were out the operation. This eventually led to questionsalso interested in the technique [120-122], its use about the ability to deliver oxygen at lower tempera-spread, and it became widely adopted as a cardioplegic tures. It was well known that the oxygen-hemoglobinmethod during the 1980s. dissociation curve was shifted to the right by hypo- Nevertheless, there are many proponents of thermia, and interfered with unloading of oxygen atcrystalloid cardioplegia [113,114,123], and other the cellular level. The question was "Did we needmethods of myocardial protection such as fibrillatory hypothermia"? If we used a warm induction dose ofarrest [124,125], who continue to use their methods cardioplegia, cold in the middle, and a "hot-shot" atwith good results. the end, did we really need the cold in the middle? Ali Dr Buckbergs group continued to work on has summarized the theoretical background andmyocardial protection and developed several very rationale of the technique [ 140,141 ].important techniques. Their work asked whether we After Salerno reintroduced the use of continu-could use cardioplegia not merely to prevent damage, ous normothermic blood cardioplegia [142], initialbut also to act as a form of treatment, and to reverse experimental [143] and clinical [144-146] work led toinjury to the myocardium. renewed interest in the technique. It led to the devel- They reported the use of warm blood cardioplegia opment of new technology in order to use the tech-given to induce cardiac arrest and replenish high- nique to advantage. Visualization could be difficult, soenergy phosphates in energy-depleted hearts before a variety of "blowers" were developed to aid the sur-giving cold cardioplegia [126]. This is important in geon [147,148]. Some investigators developed the usechronically ill patients, and also those suffering from of equipment to monitor the adequacy of perfusionacute ischemia [127]. during the operation. Other groups explored the This led to investigations altering the conditions physiological limits of the technique. Could the flowof reperfusion (pressure, temperature, etc.) at the be interrupted, and if so, for how long? This was stud-end of the arrest period. The use of terminal warm ied experimentally [149,150] and clinically [151-154].
  17. 17. History of myocardial protection There was initially some concern about the issue performed from the aorta to the coronary sinus. Thisof neurologic protection [155]. However, other in- was modified by the ligation of the coronary sinusvestigators found that the neurologic threat was not to facilitate retroperfusion of the myocardium (theseen in their studies [156-160]. A great deal of work Beck II operation). By 1954 Beck had performed theensued concerning the use of normothermic tech- operation on 43 patients and symptoms of anginaniques. This was summarized in a monograph [5]. were improved in 88% [176]. However, it was aAfter the initial flush of enthusiasm, the technique has difficult operation to perform using the technologyfound its niche, and shown that myocardial protection then available. The difficulty of the operation, earlycan be achieved with methods other than hypother- surgical failures, and deaths led to the abandonmentmia, which had become so deeply entrenched. of the procedure. In 1956 the pioneering work in cardiac surgery from the University of Minnesota extended to theRetrograde cardioplegia investigation of cardiac perfusion and cardioplegia.There was a resurgence of interest in coronary sinus Gott and Lillehei first used retrograde continuousretroperfusion of the heart in the early 1980s, led by normothermic blood cardioplegia in a dog modelGundry, Chitwood, Menasche, Fabiani, Carpentier, [78] using potassium citrate blood cardioplegia asFuentes, and Chiu, among others. Coronary sinus per- described by Melrose. They also went on to use thefusion was used initially with crystalloid cardioplegia, technique clinically in valve surgery [79,80]. However,and then with blood cardioplegia, and both were used as outlined above, other technical developments"cold." However, the need to deliver cardioplegia in superceded this technique.a near continuous fashion for the normothermic Work continued on retroperfusion in experimentaltechniques of warm heart surgery led some surgeons models. In 1967 Hammond et al. found that retro-to reexamine the retrograde route of administration perfusion provided some myocardial protection dur- [161,162]. It had been used by surgeons sporadic- ing coronary artery ligation in dogs [177]. In 1973ally over the years [163—169], but became much more Lolley et al. found that retroperfusion with substratewide-spread after the upsurge in interest in normo- enhancement gave better protection during nor-thermic techniques. mothermic ischemic arrest [178]. The technique of Thebesius first described the anatomy of the coro- retroperfusion of the heart was picked up again clinic-nary veins in 1708 [170], and this was studied further ally in the following Abernathy in 1798 and Langer in 1880. This led to There were several studies done to assess thethe work by Pratt in 1898, in which the feline heart adequacy of retrograde coronary sinus perfusion forwas supported with retrograde perfusion alone for protection of the heart, and it was especially importantup to 1 h [23]. In 1928 Wearn showed that coronary with the normothermic blood cardioplegia techniqueveins communicate with thebesian veins [24-26], and because of the question of right ventricle protectionin 1929 Grant found that effluent drained into both [163,179-182]. Most surgeons today have had someventricles. Katz showed great variability in venous experience with the retrograde route of cardioplegiaanatomy in 1938 [38]. In the same year, Gregg showed administration, and many would advocate its usethat there was increased backflow through the coron- in redo surgery or valvular surgery. Some surgeons,ary arteries when the coronary sinus was ligated [27]. such as Buckberg and Salerno, have also advocated theIn 1943 Roberts performed dye injection of the coron- use of simultaneous antegrade and retrograde deliveryary sinus, and found filling of the coronary arteries of cardioplegia to better perfuse all capillary beds[171,172]. This suggested that the heart could be [181,183-185].nourished via retrograde perfusion, and maybe usefulin the treatment of myocardial ischemia. Other subgroups of patients Dr Claude Beck tested these hypotheses in 1945.Beck was an early proponent of coronary sinus inter- The growth of cardiac surgery led investigators to tryvention [48,52-55,173-175]. He found a decrease to improve myocardial protection in various sub-in the size of an experimental myocardial infarction groups of patients. In particular, some subgroupswith ligation of the coronary veins to that area. This have a higher mortality rate, such as patients at theled to the "Beck operation," in which a bypass was extremes of age, both the very young and the very old.
  18. 18. CHAPTER 1There has been research in optimizing the methods of pleted. The history of this topic was written, and con-myocardial protection in these more extreme groups. tinues to be written, by the contributors to this book. Patients undergoing the repair of congenital heartdefects often have multiple abnormalities, not justcardiac ones. In addition, there is some evidence that Referencesthe myocardium of these patients may be different 1 Chitwood WR. Myocardial Preservation: clinical applica-from normal on a cellular level. Pediatric heart sur- tions. Philadelphia: Hanley & Belfus, 1988.geons have carried out work to improve the protection 2 Chiu RCJ, eds. Cardioplegia. Current concepts andof the heart during repair of congenital lesions in controversies. Austin TX: RG Landes, 1993.immature and newborn children [186-196]. 3 Engelman RM, Levitsky S eds. A Textbook of Cardioplegia for Difficult Clinical Problems. Mount The population in western countries is increas- Kisco, NY: Futura Publishing, 1992.ingly aging. Cardiac surgeons are operating on older 4 Roberts AJ, ed. Myocardial Protection in Cardiac Surgery.patients, with more comorbidities. This group of New York: Marcel Dekker, 1987.patients also poses special challenges for myocardial 5 Salerno TA, eds. Warm Heart Surgery. London: Arnold,protection. Several investigators have studied the 1995. 6 Krukenkamp IB, Levitsky S. Myocardial protection:changes associated with aging, and the effects on modern studies [key references]. Ann ThoracSurg 1996;myocardial protection [197-201]. The "senescent" 61:1581-2.myocardium changes as it ages, and several studies 7 Bernard C. Experimental Medicine. New Brunswick:suggest we may get better myocardial protection in Transaction Publishers, 1991.this age group by altering the cardioplegia ingredients, 8 Frank O. Zur dynamik des herzmuskels. ZBiol 1895; 32: 370-447.or by changing our strategy. 9 Frank O. Die grundform des arteriellen pulses. Z Biol There was also an enthusiasm for alternative 1899; 37:483-526.methods of achieving cardiac arrest that use potassium 10 Frank O. On the dynamics of cardiac muscle. Am Heart}channel "openers" to remove the transmembrane 1959; 58:282-317.potential [202-206]. Further work needs to be done 11 Starling EH. The Linacre Lecture on the Law of the Heart. London: Longmans, Green, and Co, 1918.before we better understand the role of this technique. 12 Ringer S. Concerning the influence exerted by each of the constituents of the blood on the contraction of the ventricle. /PhysiolLond 1880-2; 3: 380-93.Summary 13 Ringer S. A further contribution regarding the influenceOne could consider that the whole field of myocardial of different constituents of the blood on the contraction oftheheart./P/iyszo/Lond 1883; has gone almost full circle as the emphasis 14 Ringer S. A third contribution regarding the influencehas returned to the avoidance of ischemia. The other of the inorganic constituents of the blood on the ven-chapters in this book will address each topic more tricular contraction. / PhysiolLond 1883; 4:222—5.fully, but one might view the return of beating heart 15 Ringer S, Buxton D. Upon the similarity and dissimilar-surgery as the best way to avoid ischemia altogether. ity of the behavior of cardiac and skeletal muscle when brought into relation with solutions containing sodium,This is certainly a promising area for research, both calcium, and potassium salts. / Physiol Land 1887; 8:with regards to myocardial protection and neurolog- 288-95.ical functioning. We may see a change in emphasis as 16 Toledo-Pereyra LH. A study of the historical origins ofwe adopt the new paradigm of "off-pump" surgery, cardioplegia. PhD thesis. Minneapolis: University ofbut we will still need the basic concepts of myocardial Minnesota, 1984. 17 Baetjer AM, MacDonald CH. The relation of theprotection, even in that setting. We will also need to sodium, potassium and calcium ions to the heart rhyth-use methods of circulatory support and myocardial micity. AmJPhysiol 1931-2; for "open" procedures, such as valve 18 Greene CW. On the relation of inorganic salts of bloodsurgery or intracardiac repairs of congenital defects, to the automatic activity of a strip of ventricular muscle.for the foreseeable future. There will still be a need for Am JPhysiol 1898-9; 2: 82-126. 19 Howell WH. On the relation of the blood to the auto-myocardial protection. maticity and sequence of the heartbeat. Am J Physiol The topic of myocardial protection is very large. In 1898-9;2:47-81.this chapter we have given only an overview. It is a 20 Lingle DJ. The action of certain ions on ventricularstory that continues to evolve, and is not yet com- muscle. Am J Physiol 1900; 4: 265-82.
  19. 19. History of myocardial protection21 Wiggers CJ. Studies in the consecutive phases of the 42 Ross J, Jr, Klocke F, Kaiser G, Braunwald E. Effect of cardiac cycle. AmJPhysiol 1921; 56:415-59. alterations of coronary blood flow on the oxygen con-22 Zwikster GH, Boyd }E. Reversible loss of the all or none sumption of the working heart. Circ Res 1963; 13: response in cold blooded hearts treated with excess 510-13. potassium. Am]Physiol 1935; 113: 356-67. 43 Sarnoff SJ, Gilmore JP, Skinner NS, Jr, Wallace AG,23 Pratt FH. The nutrition of the heart through the vessels Mitchell JH. Relation between coronary blood flow and of Thebesius and the coronary veins. AmJPhysiol 1898; myocardial oxygen consumption. Circ Res 1963; 13: 1:86-103. 514-21.24 Wearn JT. Extent of capillary bed of heart. / Exp Med 44 Weisberg H, Katz LN, Boyd E. Influence of coronary 1928;47:273-92. flow upon oxygen consumption and cardiac perform-25 Wearn JT. Role of thebesian vessels in circulation of ance. Circ Res 1963; 13:522-8. heart. JExp Med 1928; 47:293-316. 45 Harken DE. Foreign bodies in, and in relation to,26 Wearn JT. Thebesian vessels of heart and their relation thoracic blood vessels and heart. I. Techniques for to angina pectoris and coronary thrombosis. New Engl ] approaching and removing foreign bodies from cham- Med 1928; 198: 726-7. bers of the heart. Surg Gynecol Obstet 1946; 83: 117-27 Gregg DE, Dewald D. The intermittent effects of occlu- 25. sion of the coronary veins on the dynamics of the 46 Gross RE, Hubbard JP. Surgical ligation of patent duc- coronary circulation. Am } Physiol 1938; 124:144. tus arteriosus: report of first successful case. JAMA 1939;28 Gregg DE, Dewald D. Immediate effects of coronary 112:729-31. sinus ligation on dynamics of coronary circulation. Proc 47 Blalock A, Taussig HB. The surgical treatment of SocExp BiolMed 1938; 39: 202-4. malformations of the heart in which there is pulmon-29 Gregg DE. Immediate effects of occlusion of coronary ary stenosis or pulmonary atresia. JAMA 1945; 128: veins on collateral blood flow in coronary arteries. Am J 189-202. Physiol 1938; 124:435-43. 48 Beck CS, Griswold RA. Pericardiectomy in the treat-30 Gregg DE. Immediate effects of occlusion of coronary ment of the Pick syndrome: experimental and clinical veins on dynamics of coronary circulation. AmJPhysiol observations. Arch Surg 1930; 21:1064-113. 1938; 124:444-56. 49 Hudson CL, Moritz AR, Wearn JT. The extracardiac31 Gregg DE. Effect of coronary perfusion pressure or anastomoses of the coronary arteries. J Exp Med 1932; coronary flow on oxygen usage of the myocardium. Circ 56:919-26. Res 1963; 8:497-500. 50 Moritz AR, Hudson CL, Orgain S. Augmentation of32 Hooker DR. On recovery of heart in electric shock. Am the extracardiac anastomoses of the coronary arteries JPhysiol 1929; 91:305. through pericardial adhesions. / Exp Med 1932; 56:33 Katz LN, Lindner E. Action of excess Na, Ca and K on 927-32. coronary vessels. Am J Physiol 1938; 124:155-60. 51 Gross L, Blum L, Silverman G. Experimental attempts to34 Katz LN, Mendlowitz M, Kaplan HA. Action of digitalis increase the blood supply to the dogs heart by means of on isolated heart. Am Heart J1938; 16:149-58. coronary sinus occlusion. JExp Med 1937; 65:91-108.35 Katz LN et al. Effects of various drugs on coronary 52 Beck CS. The surgical approach to diseases of the heart. circulation of denervated isolated heart of dog and cat; Trans Coll Phys Philadelphia 1939. observations on epinephrine, acetylcholine, acetyl-(3- 53 Beck CS. The coronary operation. Am Heart J 1941; 22: methylcholine, nitroglycerine, sodium nitrite, pitressin 539-44. and histamine. Arch Int Pharmacodyn Ther 1938; 59: 54 Beck CS. Revascularization of the heart. Ann Surg 1948; 399-415. 128:854.36 Katz LN, Mendlowitz M. Heart failure analyzed in 55 Beck CS, Stanton E, Batinchok W, Leiter E. isolated heart circuit. Am J Physiol 1938; 122: 262-73. Revascularization of the heart by graft of systemic37 Katz LN, Jochim K, Bohning A. Effect of extravascular artery. JAMA 1948; 137: 436-42. support of ventricles on flow in coronary vessels. Am 56 Beck CS, Hahn RS. Revascularization of the heart. J Physiol 1938; 122:236-51. Circulation 1952; 5: 801.38 Katz LN, Jochim K, Weinstein W. Distribution of cor- 57 CutlerEC, Levine SA. Cardiotomy and valvulotomy for onary blood flow. Am]Physiol 1938; 122:252-61. mitral stenosis. Experimental observations and clinical39 Reissman KR, Van Citters RL. Oxygen consumption notes concerning an operated case with recovery. Boston and mechanical efficiency of the hypothermic heart. Med Surg J1923; 188:1023-7. JAppl Physiol 1956; 9:427-30. 58 Souttar HS. The surgical treatment of mitral stenosis.40 McKeever W, Gregg DE, Canney P. Oxygen uptake Br Med /1925:603-6. of the nonworking left ventricle. Circ Res 1958; 6: 612- 59 Harken DE, Dexter L, Ellis LB, Farrand RE, Dickson JF. 23. The surgery of mitral stenosis III. Finger-fracture valvu-41 Kahler RL, Braunwald E, Kelminson LL, Kedes L, loplasty. Ann Surg 1951; 134: 722. Chidsey CA. Effect of alterations of coronary blood flow 60 Brock RC. Pulmonary Valvotomy for the Relief of on the oxygen consumption of the nonworking heart. Congenital Pulmonary Stenosis. Report of three cases. Circles 1963; 13: 501-9. Br Med] 1948:1121-6.
  20. 20. CHAPTER 161 Gross RE, Watkins E, Pomeranz AA, Goldsmith El. A 79 Gott VL, Gonzalez JL, Zuhdi MN, Varco RL, Lillehei method for surgical closure of interauricular septal CW. Retrograde perfusion of the coronary sinus for defects. Surg Gynecol Obstet 1953; 96:1-24. direct vision aortic surgery. Surg Gynecol Obstet 1957;62 Bigelow WG, Lindsay WK, Greenwood WF. Hypo- 104:319-28. thermia its possible role in cardiac surgery. An investi- 80 Lillehei CW, DeWall RA, Gott VL, Varco RL. The direct gation of factors governing survival in dogs at low body vision correction of calcine aortic stenosis by means of a temperatures. Ann Surg 1950; 132: 849-66. pump-oxygenator and retrograde coronary sinus perfu-63 Bigelow WG, Lindsay WK, Harrison RC, Gordon RA, sion. Dis Chest 1956; 30:123-32. Greenwood WF. Oxygen transport and utilization in 81 Gerbode F, Melrose DG. The use of potassium arrest in dogs at low body temperature. Am J Physiol 1950; 160: open cardiac surgery. Am J Surg 1958; 96:221-7. 125-37. 82 Allen P, Lillehei CW. Use of induced cardiac arrest in64 Bigelow WG, Callaghan JC, Hopps JA. General open-heart surgery. Minn Med 1957; 40:672. hypothermia for experimental intracardiac surgery. 83 Bjork VO, Fors B. Induced cardiac arrest. / Thorac Ann Surg 1950; 132: 531-40. Cardiovasc Surg 1961; 41: 387-94.65 Boerema I, Wildschut A, Schmidt WJH, Broekhuysen L. 84 MacFarland JA, Thomas LB, Gilbert JW, Morrow AG. Experimental researches into hypothermia as an aid in Myocardial necrosis following elective cardiac arrest the surgery of the heart. Arch Chir (Neerl) 1951; 3: induced with potassium citrate. / Thorac Cardiovasc 25-34. Surg 1960; 40:200-8.66 Cookson BA, Neptune WB, Bailey CP. Hypothermia as 85 Nunn DD, Belisle CA, Lee WH. A comparative study of a means of performing intracardiac surgery under direct aortic occlusion alone and of potassium citrate arrest vision. Dis Chest 1952; 22: 245-60. during cardiopulmonary bypass. Surgery 1959; 45: 848.67 Swan H, Zeavin I, Blount SG, Jr, Virtue RW. Surgery by 86 Waldhausen JA, Braunwald NS, Bloodwell RD, direct vision in the open heart during hypothermia. Cornwell WP, Morrow AG. Left ventricular function JAMA 1953; 153:1081-5. following elective cardiac arrest. / Thorac Cardiovasc68 Swan H, Zeavin I, Holmes JH, Montgomery V. Cessa- Surg 1960; 39: 799-807. tion of circulation in general hypothermia. I. Physiologic 87 Willman VL, Cooper T, Zafiracopoulos P, Hanlon CR. changes and their control. Ann Surg 1953; 138:360-76. Depression of ventricular function following elective69 Bigelow WG, Mustard WT, Evans JG. Some physiolog- cardiac arrest with potassium citrate. Surgery 1959; 46: ical concepts of hypothermia and their application to 792-6. cardiac surgery. / Thorac Cardiovasc Surg 1954; 28:463. 88 Hoelscher B, Just OH, Merker HF. Studies by electron70 Swan H, Zeavin I. 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