Pathophysiology and Rational Pharmacotherapy of Myocardial Ischemia PDF
Preview Pathophysiology and Rational Pharmacotherapy of Myocardial Ischemia
Pathophysiology and Rational PharmacotherapyofMyocardialIschemia Gerd Heusch (Ed.) Pathophysiology and Rational Pharmacotherapy of Myocardial Ischemia With contributions by P. B. Corr .J. Dirschinger . K. Egstrup . K. P. Gallagher B. D. Guth· J.Herlitz -B. Heusch· G. Heusch· A. Hjalmarson Th. Hohlfeld .J. C. Kaski ·M.Kobayashi· F.Kraus ' A.Malliani A. Maseri· H. A.McCann .L. H. Opie . S.M. Pogwizd W. Rafflenbeul· G. Reiniger-J. Ross,Jr..W. Rudolph· J. Schaper W. Schaper- R. J.Schott ·K.Schrör·M.Schwaiger' F.Waagstein H. G. Wolpers Springer-Verlag Berlin Heidelberg GmbH The Editor: Prof. Dr.med. GerdHeusch Abteilungfür Pathophysiologie Zentrumfür InnereMedizin UniversitätsklinikumEssen Hufelandstraße55 D-4300Essen, FRG CIP-TitelaufnahmederDeutschenBibliothek Pathophysiologyandrationalpharmacotherapyormyocardialischemia1GerdHeusch(ed.),With contributionsbyP.B. Corr... - Darmstadt:Steinkopff;NewYork:Springer,1990 ISBN978-3-642-54135-3 ISBN978-3-642-54133-9(eBook) DDI 10.1007/978-3-642-54133-9 NE:Heusch,Gerd[Hrsg.];Corr,PeterB. [Mitverf.] Thisworkissubjecttocopyright. Allrightsarereserved,whetherthewholeorpartofthematerialis concemed,specificallytherightsoftranslation,reprinting,re-useofillustrations,recitation,broad-cast ing,reprodcutiononmicrofilmsorinotherways,andstorageindatabanks.Duplicationofthispublica tionorpartsthereofisonlypermittedundertheprovisionoftheGermanCopyrightLawofSeptember9, 1965, in its version of June 24, 1985, and a copyright fee must a1ways be paid. Violations fallundertheprosecutionactoftheGermanCopyrightLaw. Copyright©1990bySpringer-Verlag BerlinHeidelberg Originallypublished byDr.DietrichSteinkopffVeriagGmbH& Co. KG,Darmstadtin 1990. Softcoverreprintofthehardcover Istedition 1990 MedicalEditorial:SabineMüller - EnglishEditor:JamesC.Willis- Production:HeinzJ.Schäfer Tbeuseofregisterednames,trademarks,etc.,inthispublicationdoesnotimply,evenintheabsenceof aspecificstatement,thatsuchnamesareexemptfromtherelevantprotectivelawsandregulationsand thereforefreeforgeneraluse. Printedonaced-freepaper Foreword Ischemieheart diseaseisstillthe mostfrequent causeofdeathinthewesternworld. There have beensignificantachievements indiagnosticprocedures aswellasinthe medical, invasive,andsurgiealtreatmentofischemieheartdiseaseinrecentyears.A varietyofdrugsareavailableforthepharmacotherapyofischemieheartdisease,par ticularly nitrates, ß-blockers, and calcium-antagonists which are used as mono therapyor invarious combinations.However, the selection ofpatientsforacertain treatment, as weIl as the optimization of an individual treatment are still largely empirical. On the other hand, the recent advances in experimental cardiology emphasize the extremely complex and dynamie scenario ofischemicheart disease, involving endothelial damage, coagulation processes, metabolie and morphologie derangements, coronary constrictor mechanisms, blood flow redistribution, arrhythmogenesis, contraetile dysfunction during ischemia and reperfusion, and finallylack or presenceofpain perception.Therefore, it appearsdesirable to close the gap between experimental and clinical cardiology and, thus, to provide a pathophysiologiealbasisfor rationalcliniealdecisionswithrespect todiagnostic and therapeuticprocedures. The idea for thisbook arose during the preparationofaseminarserieson experi mentalcardiology, when Ifound itdiffieulttocollectthepertinentinformationfrom textbooksofcardiology,physiology,pathology, and pharmacology, aswellasfrom numerousreviewandoriginal artieiesonspecifictopies.Iamnowverygrateful that expertcliniealandexperimentalcolleaguesfromaroundtheworldhavejoinedmein the effort to provide a comprehensivetextbookon the pathophysiologyofmyocar dialischemiaand itsrationalpharmacotherapy. Finally,Iwouldliketothankthepublisher,inpartieularMs.SabineMüllerforthe pleasantcooperationand constructive supportineditingthisbook. Essen,spring 1990 GerdHeusch v Contents Foreword . v 1.ABriefHistoryofAnginaPectoris:ChangeofConeeptsandIdeas BeateHeusch,BrianD. Guthand GerdHeusch . 1 2.MyoeardialUltrastructureinIsehemia JuttaSchaper . 11 3.MyoeardialMetabolisminIsehemia LionelH.Opie .. . . . . . . . . . . 37 4.MetabolieImagingofisehemieHeartDiseasebyPositronEmission Tomography HansGeorgWolpersandMarkusSchwaiger . 59 5.Coagulation,ThrombosisandFibrinolysisinMyoeardialIsehemia ThomasHohlfeldandKarstenSchrör . . . . . . . . . . . . . . 83 6.RegionalMyoeardialFlow-FunetionRelationshipinIsehemia Kim P.Gallagher . . . . . . . . . . . . . . . . . . . . . . . . .. 111 7.ElectrophysiologicandBiochemicalMechanismsUnderlyingMalignant VentrieularArrhythmiasduringEarlyMyoeardialIsehemia StevenM.Pogwizd andPeterB.Corr . . . . . . . . . . . . . . . . . . . 137 8.ReperfusedMyoeardium:Stunning,Preconditioning,andReperfusionInjury WolfgangSchaper, RobertJ.SchottandMasaoKobayashi . . . . . . . . . . 175 9.CoronaryVasomotorToneinMyocardiallsehemia GerdHeuschandBrianD. Guth . 199 10.CliniealSignifieaneeofCoronaryVasomotorToneinMyoeardialIsehemia JuanCarlosKaski andAttilioMaseri . . . . . . . . . . . . . . . . . . . .. 217 11.TheChallengeofSilentMyoeardialIsehemia AlbertoMalliani 231 VII u.Exercise-InducedMyocardialIschemia:TheRoleofHeartRateReduction inTherapeuticApproach Brian D. Guthand GerdHeuseh . . . . . . . . . . . . . . . . . . . . . . . 247 13.TreatmentofMyocardialIschemiawithBeta-Blockers ÄkeHjalmarson,JohanHerlitzand FinnWaagstein . . . . . . . . . . 261 14.TreatmentofMyocardialIschemiawithNitrates WernerRudolph,GünterReiniger,JosefDirsehingerand FelieitasKraus . . . . . . . 275 15.TreatmentofMyocardialIschemiawithCalciumAntagonists WolfRafflenbeuI . . . . . . . . . . . . . . . . . . . . . . . 295 16.CombinationAnti-AnginalTherapy:RationaleandResults Hugh A. McCann and John Ross,Jr . . 315 17.CombinedTreatmentofStableEtTort-InducedAnginaandMixedAngina KennethEgstrup 331 SubjectIndex . . 349 VIII ABrief History of Angina Pectoris: Change of Concepts and Ideas BeateHeusch,Brian D. Guth, and GerdHeusch Abt. für Pathophysiologie,UniversitätsklinikumEssen and Dept. ofMedicine, UniversityofCalifornia, SanDiego, USA Thehistoryofanginapectorismaybeconsideredinthreedevelopmentalperiods.The firstextendedfromantiquityintothelatemiddleagesduringwhichnumerousdescrip tionsofclinicalsymptomsappearedthat,inretrospect,werelikelyanginapectorisbut at the time were not associated withadisease ofthe heart. The periodfrom the late middle agesto the early 20thcenturybroughtabout the correlationbetween angina pectorisandapathologicalstateofthecoronaryvessels.FinaIly,sincethe1930sthere has been the development of pathophysiological concepts of angina pectoriswhich nowfocusonan impairedrelationbetweenthe work performedbythe heartand the oxygensupplytothe heartthroughthecoronarycirculation. The earliestdescriptionofadiseasewhichmaybecharacterizedasanginapectoris isfound intheEgyptianPapyrus Ebers(Fig. 1)whichoriginatesfrom 1500B.C. The contentofthe PapyrusEbersdates back toanevenolderdynasty (2500-2000B.C.) [8]:"Ifyoufindaman whoseehesthurts andwhosuffers painfrom hisshoulderand hisstornach,youshaIlsaythatdeathisapproaching". Herealreadyistheassociation of angina-like ehest pain radiating into the shoulder with a fatal result. These symptoms were,however,relatedtoadisease ofthestornach,consequentlyherbs to elicitvomiting and diarrheawere the recommendedtreatment. The term "angina" is first found in writings ascribed to the Greek physician Hippocrates (460-370 B.C.) [10, 14]. Chest pain radiating into the shoulder and arm, also inconnection with dyspnea, iscaIledxuvaYXtj. This term iscomposedof xudrv (the dog) and aYXill (to narrow, to compress). Apparently Hippocrates regarded angina pectoris and angina tonsillaris - diseases of the throat associated with a typical "barking" voice - as the same disease. A weIl known letter trom SenecatoLucilius(originating60-65A.D.)describes pectanginalsymptoms inhim self, symptoms which were caIled "meditatio mortis" (preparation of death) by the physicians. InthiscontextTacitus'sdescriptionofSeneca'ssuicideisinteresting. He could only bleed to death after he was carried into a warm bath, because his extremities were hardened - an indication of generalized atherosclerosis. Galen caIledanginapectoris"Kardialgia"[25].Thedesignationofboth theupperportionof the stornach and the heart bythe term "Kardia" isprobably not accidental. Galen knew thatthe vagalnerves innervateboth the stornach and the heartand attributed heart burn and tachycardia to a "sympathetic" radiation from the stomach to the heart. Apart from the fact that Galen anticipated modern ideas about autonomous reflexes, eventoday aclinicaldifferentialdiagnosisbetweenanacute,painfuldisease of the stornach and an anginal attack may be difficult. This ambivalent nosological relation between heart and stornach persists alsointo today's nomenclature, inthat ventricle means"!ittle stornach". 1 Fig.1.PapyrusEbers Until the late middle ages medicine was committed to Galen's ideas, including thoseaboutanginapectoris. However,graphicsbyLeonardoda Vinci (1452-1519) (Fig. 2) andAndreasVesalius(1514-1564) provethattheanatomyoftheheartand the coronary vessels were known in great detail. According to the prevailingidea, however, thecoronaryveins functionedto bringnutritivebloodfromtheliverto the heart [22]. This conceptpersisteduntil1628whenW.Harveypublishedhis"ExercitatioAna tomicade MotuCordiset Sanguinis" (Fig. 3), inwhichhenot only describedthecir culation of blood through the lungs and the body, but also described the supply of bloodtotheheartbythecoronaryarteries.Thus,theinitialperiodintheunderstand ing of angina pectoris endedwith a knowledge of its symptomsbut ideas aboutthe genesis ofthis diseaseanditsrelationto theheartremainedunclear. In1761,Morgagnicharacterizedthepathologyoftypicalcoronaryatherosclerosis at autopsy. Progressintheunderstandingof anginapectorisexceedingthe morpho logy of coronary atherosclerosis was provided by British clinicians in the late 18th century. The surgeon lohn Hunter suffered from angina pectoris and studied the symptoms carefully in himself. He noticed the provocation of anginal attacks by physical exercise. In 1793 he died during an anginal attack after he became very excitedin adiscussionduringroundsinSt.George'sHospital. lohnHunteris, thus, aclassicexamplefor theacuteprecipitationofanginapectorisbyphysicalandmental stress.Athisautopsyamarkedossificationofthecoronaryarterieswasrevealed[1]. In1768W. Heberdengave hisclassiclectureon anginapectoristo theRoyalCollege of Physicians which was published 4 years later. On the basis of numerous clinical observations,he describedthetypicalpainsensation,the provocationofanginapec toris by physicalexercise andopulent meals, and the higherincidence in men, par ticularlyin thoseolderthan50years.Heberden,whosenameisused todayto desig nate the poststenoticmyocardial ischemia on the basis of coronary atherosclerosis, 2 Fig.2.Illustrationofthe heartbyLeonardodaVinci consideredcoronaryspasm asthe causeofangina pectoris. Consequently,herccom mendedopiumand alcohol for therapy. In 1809A.Bumswasthe firsttodevelopapathophysiologicalconceptforthe rela tion between the clinical anginal symptoms and the coronary atherosclerosis at autopsy. He argued that the diseased heart, like an extremity with a tourniquet, could not increaseitsfunction withoutan adequateincreaseinbloodflow, and that cardiac failure would result from the excessive demand. This concept remained hypotheticaluntil itwaslaterconfirmedbyexperimentalinvestigationsinthe course ofthenineteenthcentury. In 1881the GermanpathologistsCohnheimandv.Schult heiss-Rechberg, using animal experiments, characterized the coronary arteries as functional end-arteries,suchthattheirocclusion leads to irreversible lossofthe per fused myocardialarea.Theyattributedthe lossofcardiacfunction and the initiation ofventricularfibrillationaftercoronaryligation,not tothe lackofoxygen, buttothe accumulationofmetaboliebyproductsdue to the lackofwashout. Crucial for the developmentofmore preciseideas aboutmyocardialischemia was the development of appropriate experimental models.In 1912Morawitzand Zahn [16]developed a coronary sinus cannulawhich first permitted the measurement of coronary blood flow in situ. Progress in the diagnosis and therapy of the clinical symptomsoccuredin 1867asL. Bruntonfirst describedin"Lancet"the therapeutic 3
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