Abstract
The conspicuous effects of ischemia on the electrocardiogram quickly caught the attention of clinicians who exploited them to diagnostic advantage. These electrocardiographic changes called for an explanation, which meant a description of the cellular electrophysiologic changes during ischemia that generated the electrocardiographic abnormalities. Although direct evidence bearing on the problem was scarce, constructs and schemas were plentiful. Textbooks of electrocardiography proudly displayed resting and action potentials from ischemic cells even before the technology for intracellular recording was well developed. The bases for these conceptions were the wellknown depolarizing effect of injury on excitable cells and the idea that the duration of the action potential of ischemic cells was abbreviated. Explanations were built on the perception that the basic changes produced by ischemia were few and simple: partial depolarization, abbreviation of the action potential, or total loss of electrical activity because of cell death. Even after the development of intracellular recording, direct observations of cellular electrophysiologic changes during ischemia have been difficult and sparce. The true condition of ischemia occurs in the setting of the beating heart working under load and supplied with blood by the coronary circulation. Under these conditions intracellular recording is taxing, imprecise, and confined to the epicardial surface. Nonetheless, early recordings during acute ischemia confirmed the idea that ischemia caused a decrease in amplitude of the resting potential and abbreviation of the action potential [1, 2].
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Kardesch M, Hogancamp CE, Bing RJ: Effect of complete ischemia on the intracellular electrical activity of the whole mammalian heart. Circ Res 6: 715–725, 1958.
Samson WE, Scher AM: Mechanism of S-T segment alteration during acute myocardial injury. Circ Res 18. 8: 780–787, 1960.
Bishop SP, White FC, Bloor CM: Regional myocardial blood flow during acute myocardial infarction in the conscious dog. Circ Res 38: 429–438, 1976.
Trautwein W, Gottstein U, Dudel J: Der Aktionsstrom der myokardfaser un sauerstoffmangel. Pflugers Arch 260: 40–60, 1954.
Coraboeuf E, Gargouil YM, Laplaud J, Desplaces A: Action de l’anoxie sur les potentiels electriques des cellules cardiaques de mammiferes actives et enertes (tissu ventriculaire isole de cobaye). C R Acad Sci [D] (Paris) 246: 3100–3103.
Webb JL, Hollander PB: Metabolic aspects of the relationship between the contractility and membrane potentials of the rat atrium. Circ Res 4: 618–626, 1956.
Moore DJ: Potassium changes in the functioning heart under conditions of ischemia and congestion. Am J Physiol 123: 443–447, 1938.
Harris AS, Bisteni A, Russel RA, Brigham JC, Firestone JE: Excitatory factors in ventricular tachycardia resulting from myocardial ischemia: potassium a major excitant. Science 119: 200, 1954.
Regan TJ, Harman MA, Lehan PH, Burke WM, Odelwurtel HA: Ventricular arrhythmias and potassium transfer during myocardial ischemia and intervention with procainamide, insulin, or glucose solution. J Clin Invest 46: 1657–1668, 1967.
Jennings RB, Crout JR, Smetters GW: Studies on distribution and localization of potassium in early myocardial ischemic injury. Arch Pathol 63: 586–592, 1957.
Hill JL, Gettes LS: Effect of acute coronary artery occlusion on local myocardial extracellular K+ activity in swine. Circulation 61: 768–778, 1980.
Vleugels A, Vereecke J, Carmeliet E: Ionic currents during hypoxia in voltage-clamped cat ventricular muscle. Cire Res 47: 501–508, 1980.
Bassingthwaighte JB, Fry CH, McGuigan JAS: Relationship between internal calcium and outward current in mammalian ventricular muscle: a mechanism for the control of the action potential duration? J Physiol (Lond) 262: 15–37, 1976.
Carmeliet E: Chloride and potassium permeability in cardiac Purkinje fibers. Bruxelles: Arscia et Press Acad Europ, 1961.
Schwartz A, Wood JM, Allen JC, Bornet E, Entman ML, Goldstein MA, Sordahl LZ, Suzuki M, Lewis RM: Biochemical and morphologic correlates of cardiac ischemia. I. Membrane systems. Am J Cardiol 32: 46–61, 1973.
Rau EE, Shine KI, Langer GA: Potassium exchange and mechanical performance in anoxic mammalian myocardium. Am J Physiol 232: H85, 1977.
Friedman PL, Stewart JR, Fenoglio JJ Jr, Wit AL: Survival of subendocardial Purkinje fibers after extensive myocardial infarction in dogs: in vitro and in vivo correlation. Circ Res 33: 597–611, 1973.
Friedman PL, Stewart JR, Wit AL: Spontaneous and induced cardiac arrhythmias in subendocardial Purkinje fibers after extensive myocardial infarction in dogs. Circ Res 33: 612–625, 1973.
Lazzara R, El-Sherif N, Scherlag BJ: Electrophysiological properties of Purkinje cells in one-day-old myocardial infarction. Circ Res 33: 722–734, 1973.
Friedman PL, Fenoglio JJ, Wit AL: Time course for reversal of electrophysiological and ultrastructural abnormalities in subendocardial Purkinje fibers surviving extensive myocardial infarction. Circ Res 36: 127–144, 1975.
Lazzara R, El-Sherif N, Scherlag BJ: Disorders of cellular electrophysiology produced by ischemia of the canine His bundle. Circ Res 36: 444–453, 1975.
Ten Eick RE, Singer DH, Solberg LE: Coronary occlusion: effect on cellular electrical activity of the heart. Med Clin North Am 60: 49–67, 1976.
Singer DH, Baumgarten CM, Ten Eick RE: Cellular electrophysiology of ventricular and other dysrhythmias: studies on diseased and ischemic heart. Prog Cardiovasc Dis 24: 97–156, 1981.
Ten Eick RE, Baumgarten CM, Singer DH: Ventricular dysrhythmia: membrane basis or of currents, channels, gates and cables. Prog Cardiovas Dis 24: 157–188, 1981.
Myerburg RJ, Gelband H, Nilsson K, Sung RJ, Thurer RJ, Morales AR, Bassett AL: Long term electrophysiological abnormalities resulting from experimental myocardial infarction in cats. Circ Res 42: 73–84, 1977.
Spear JF, Horowitz LN, Hodess AB: Cellular electrophysiology of human myocardial infarction. I. Abnormalities of cellular activation. Circulation 59: 247–256, 1979.
Lazzara R, Scherlag BJ: The role of the slow current in the generation of arrhythmias in ischemic myocardium. In: Zipes DP, Bailey JC, Elharrar V (eds) The slow inward current and cardiac arrhythmias. The Hague: Martinus Nijhoff, 1980, pp 399–416.
Lazzara R, El-Sherif N, Hope RR, Scherlag BJ: Ventricular arrhythmias and electrophysiological consequences of myocardial ischemia and infarction. Circ Res 42: 740–749, 1978.
Lazzara R, EI-Sherif N, Scherlag BJ: Early and late effects of coronary artery occlusion on canine Purkinje fibers. Circ Res 33: 597–611, 1973.
Corr PB, Cain ME, Witkowski FX, Price DA, Sobel BE: Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides. Circ Res 44: 822–832, 1979.
Sobel BE, Corr PB, Robinson AK, Goldstein RA, Witkowski FX, Klein MS: Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium. J Clin Invest 62: 546–553, 1978.
Arnsdorf MF, Sawicki GJ: The effects of lysophosphatidylcholine, a toxic metabolite of ischemia, on the components of cardiac excitability in sheep Purkinje fibers. Circ Res 49: 16–30, 1981.
Katz AM, Messineo FC: Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48: 1–16, 1981.
Hearse DJ, Yellon DM: The “border zone” in evolving myocardial infarction: controversy or confusion? Am J Cardiol 47: 1221–1334, 1981.
Simson MB, Harden W, Barlow C, Harken AH: Visualization of the distance between perfusion and anoxia along an ischemic border. Circulation 60: 1151–1155, 1979.
Baumgarten CM, Cohen CJ, McDonald TF: Heterogeneity of intracellular potassium activity and membrane potential in hypoxic guinea pig ventricle. Circ Res 49: 1181–1189, 1981.
Czarnecka M, Lewartowski B, Prokopczyk A: Intracellular recordings from the in situ working heart in physiological conditions and during acute ischemia and fibrillation. Acta Physiol Pol 24: 331–337, 1973.
Downar E, Janse MJ, Durrer D: The effect of acute coronary artery occlusion on subendocardial trans-membrane potentials in the intact porcine heart. Circulation 56: 217–224, 1977.
Russell DC, Oliver MF, Wojtczak J: Combined electrophysiological technique for assessment of the cellular basis of the early ventricular arrhythmias. Lancet 1: 686–688, 1977.
Kleber AG, Janse MJ, Van Capelle FJL, Durrer D: Mechanism and time course of S-T and T-Q segment changes during acute regional myocardial ischemia in the pig heart determined by extracellular recordings. Circ Res 42: 603–613, 1978.
Cardinal R, Janse MJ, Van Eeden I, Werner G, d’Alnoncourt CN, Durrer D: The effects of lidocaine on intracellular and extracellular potentials, activation, and ventricular arrhythmias during acute regional ischemia in the isolated porcine heart. Circ Res 49: 792–806, 1981.
Lazzara R, Hope RR, El-Sherif N, Scherlag BJ: Effects of lidocaine on hypoxic and ischemic cardiac cells. Am J Cardiol 41: 872–879, 1978.
Morena H, Janse MJ, Fiolet JWT, Krieger WJG, Crijns H, Durrer D: Comparison of the effects of regional ischemia, hypoxia, hyperkalemia and acidosis on intracellular and extracellular potentials and metabolism in the isolated porcine heart. Circ Res 46: 634–646, 1980.
Downar E, Janse MJ, Durrer D: The effect of “ischemic” blood on transmembrane potentials of normal porcine ventricular myocardium. Circulation 55: 455–462, 1977.
Janse MJ, Van Capelle FJL, Morsink H, Kleber AG, Wilms-Schopmen F, Cardinal R, d’Alnoncourt CN, Durrer D: Flow of “injury” current and pattern of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts: evidence for two different arrhythmogenic mechanisms. Circ Res 47: 151–165, 1980.
Janse MJ, Kleber AG: Electrophysiological changes and ventricular arrhythmias in the early phase of regional myocardial ischemia. Circ Res 49: 1069–1081, 1981.
El-Sherif N, Smith RA, Evans K: Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits. Circ Res 49: 255–265, 1981.
Wit AL, Allessie MA, Bonke FIM, Lamemrs W, Smeets J, Fenoglio JJ Jr: Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses: experimental approach and initial results demonstrating reentrant excitation. Am J Cardiol 49: 166–185, 1982.
Harris AS, Rojas AG: The initiation of ventricular fibrillation due to coronary occlusion. Exp Med Sug 1: 105–122, 1943.
Waldo AL, Kaiser G: A study of ventricular arrhythmias associated with acute myocardial infarction in the canine heart. Circulation 47: 1222–1228, 1973.
Boineau JP, Cox JL: Slow ventricular activation in acute myocardial infarction: a source of reentrant premature ventricular contractions. Circulation 48: 702–713, 1973.
Scherlag BJ, El-Sherif N, Hope RR, Lazzara R: Characterization and localization of ventricular arrhythmias resulting from myocardial ischemia and infarction. Circ Res 35: 372–383, 1974.
EI-Sherif N, Scherlag BJ, Lazzara R, Hope RR: Reentrant ventricular arrhythmias in the late myocardial infarction. I. Conduction characteristics in the infarction zone. Circulation 55: 686–701, 1977.
De Mello WC: Effect of intracellular injection of calcium and strontium on cell communication in heart. J Physiol 250: 231–245, 1975.
De Mello WC: Influence of the sodium pump on intracellular communication in heart fibers: effect of intracellular injection of sodium ion on electrical coupling. J Physiol 263: 171–197.
De Mello WC: Intracellular injection of H+ on the electrical coupling in cardiac Purkinje fibers. Cell Biol Int Rep 4: 51–58, 1980.
Wojtczak J: Contractures and increase in internal longitudinal resistance of cow ventricular muscle induced by hypoxia. Circ Res 44: 88–95, 1979.
Spach MS, Miller WT III, Geselowitz DB, Barr RC, Kootsey JM, Johnson EA: The discontinuous nature of propagation in normal canine cardiac muscle. Circ Res 48: 39–54, 1981.
McDonald TF, MacLeod DP: Metabolism and the electrical activity of anoxic ventricular muscle. J Physiol (Lond) 229: 559–582, 1973.
Payet MD, Schanne OF, Ruiz-Ceretti E, Demers JM: Slow inward and outward currents of rat ventricular fibers under anoxia. J Physiol (Paris) 74: 31–35, 1978.
Watanabe AM, Besch HR Jr: Cyclic adenosine monophosphate modulation of slow calcium influx channels in guinea pig hearts. Circ Res 35: 316–324, 1974.
Schneider JA, Sperelakis N: The demonstration of energy dependence of the isoproterenol-induced transcellular Cat+ current in isolated perfused guinea pig hearts: an explanation for the mechanical failure of ischemic myocardium. J Surg Res 16: 389–403, 1974.
Wissner SB: The effect of excess lactate upon the excitability of the sheep Purkinje fiber. J Electrocardiol 7: 17–26, 1974.
Coraboeuf E, Deroubaix E, Hoerter J: Control of ionic permeabilities in normal and ischemia heart. Circ Res (Suppl 1 ) 38: 92–97, 1976.
Gettes LS, Reuter H: Slow recovery from inactivation of inward currents in mammalian myocardial fibers. J Physiol 240: 703–704, 1974.
Chen CM, Gettes LS: Combined effects of rate, membrane potential and drugs on maximum rate of rise (V max) of action potential upstroke of guinea pig papillary muscle. Circ Res 38: 464–469, 1976.
Hope RR, Scherlag BJ, EI-Sherif N, Lazzara R: Heirarchy of ventricular pacemakers. Circ Res 39: 883–888, 1976.
Allen JD, Brennan JF, Wit AL: Actions of lidocaine on transmembrane potentials of subendocardial Purkinje fibers surviving in infarcted canine hearts. Circ Res 43: 470, 1978.
Rosenshstraukh LV, Brachmann J, Scherlag BJ, Harrison L, Lazzara R: Mechanisms of ventricular automaticity in the normal and infarcted dog heart {abstr}. Clin Res 29: 235A, 1981.
Dangman KH, Hoffman BF: Effects of nifedipine on electrical activity of cardiac cells. Am J Cardiol 46: 1059–1067, 1980.
El-Sherif N, Zeiler R, Gough WB: Effects of catecholamines, verapamil, and tetrodotoxin on triggered automaticity in canine ischemic Purkinje fibers {abstr}. Circulation (Suppl 2 ) 62: 281, 1980.
Kass RS, Lederer WJ, Tsien RW, Weingart R: Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibers. J Physiol (Lond) 281: 187–208, 1978.
Allessie MA, Bonke FIM, Schopman FJG: Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. “The leading circle” involvement of an anatomical obstacle. Circ Res 41: 9–18, 1977.
Katzung BG, Hondeghem LM, Grant AO: Cardiac ventricular automaticity induced by current of injury. Pflugers Arch 360: 193–197, 1975.
Katzung BG, Morgenstern JA: Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium. Circ Res 40: 105–111, 1977.
Jalife J, Moe GK: Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole. Circ Res 39: 801–808, 1976.
Antzelevitch C, Jalife J, Moe GK: Characteristics of reflection as a mechanism of reentrant arrhythmias and its relationship to parasystole. Circulation 61: 182–191, 1980.
Hoffman BF: The genesis of cardiac arrhythmias. Prog Cardiovasc Dis 8: 319–329, 1966.
Moe GK, Mendez C: Physiological basis of premature beats and sustained tachycardia. N Engl J Med 288: 250–254, 1973.
Janse MJ, Van Capelle FJL: Electrotonic interactions across an inexcitable region as a cause of ectopic activity in acute regional myocardial ischemia. Circ Res 50: 527–537, 1982.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Lazzara, R., Scherlag, B.J. (1984). Cellular Electrophysiology and Ischemia. In: Sperelakis, N. (eds) Physiology and Pathophysiology of the Heart. Developments in Cardiovascular Medicine, vol 34. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1171-4_20
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1171-4_20
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-1173-8
Online ISBN: 978-1-4757-1171-4
eBook Packages: Springer Book Archive