The Ib phase of ventricular arrhythmias in ischemic in situ porcine heart is related to changes in cell-to-cell electrical coupling. Experimental Cardiology Group, University of North Carolina.

BACKGROUND This study was designed to test the hypothesis that the loss of cell-to-cell electrical interaction during ischemia modulates the amplitude of ischemia-induced TQ-segment depression (ie, the injury potential) and the occurrence of ventricular fibrillation (VF) during the so-called Ib phase of ventricular arrhythmias. METHODS AND RESULTS Regional ischemia was induced by 60 minutes of mid-left anterior descending coronary artery ligation in open-chest swine (n = 10). Cell-to-cell electrical uncoupling was defined as the onset of the terminal rise in whole-tissue resistivity (Rt). Local activation times and TQ-segment changes (injury potential) were determined from unipolar electrograms. Extracellular K+ ([K+]e) and pH (pHe) were measured with plunge-wire ion-selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence of VF was positively correlated to the onset of cell-to-cell electrical uncoupling (R2 = .885). Cell-to-cell electrical uncoupling superimposed on changes of [K+]e and pHe contributed to the failure of impulse propagation between 19 and 30 minutes after the arrest of perfusion. During ischemia, maximum TQ-segment depression was -10 mV at 19 minutes, after which TQ-segment depression slowly recovered. The onset of the TQ-segment recovery was correlated to the second rise in Rt (R2 = .886). CONCLUSIONS In the regionally ischemic in situ porcine heart, loss of cell-to-cell electrical interaction is related to the occurrence of VF and changes in the amplitude of the injury current. Cellular electrical uncoupling contributes to failure of impulse propagation in the setting of altered tissue excitability as a result of elevated [K+]e and low pHe. These data indicate that Ib arrhythmias and ECG changes during ischemia are influenced by the loss of cell-to-cell electrical interaction.

[1]  H. C. Burger,et al.  Specific electric resistance of body tissues. , 1961, Physics in medicine and biology.

[2]  H. Poliwoda.  The Thrombolytic Therapy of Acute Myocardial Infarction , 1966, Angiology.

[3]  D. Durrer,et al.  Re-entry and ventricular arrhythmias in local ischemia and infarction of the intact dog heart. , 1971, Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen. Series C. Biological and medical sciences.

[4]  B. Nielsen,et al.  ST‐Segment Elevation in Acute Myocardial Infarction: Prognostic Importance , 1973, Circulation.

[5]  R. C. Weast.  CRC Handbook of Chemistry and Physics , 1973 .

[6]  R Lazzara,et al.  Characterization and Localization of Ventricular Arrhythmias Resulting from Myocardial Ischemia and Infarction , 1974, Circulation research.

[7]  W. C. Mello,et al.  Effect of intracellular injection of calcium and strontium on cell communication in heart. , 1975 .

[8]  O. H. Leblanc,et al.  Polymer membrane sensors for continuous intravascular monitoring of blood pH. , 1976, Journal of applied physiology.

[9]  J. L. Hill,et al.  Flexible valinomycin electrodes for on-line determination of intravascular and myocardial K+. , 1978, The American journal of physiology.

[10]  R. D. Bauer,et al.  The Arterial system : dynamics, control theory, and regulation , 1978 .

[11]  V. Wiegand,et al.  Early Mortality Due to Ventricular Fibrillation, and the Vulnerability of the Heart Following Acute Experimental Coronary Occlusion: Possible Mechanisms and Pharmacological Prophylaxis , 1978 .

[12]  D Durrer,et al.  Mechanism and Time Course of S‐T and T‐Q Segment Changes during Acute Regional Myocardial Ischemia in the Pig Heart Determined by Extracellular and Intracellular Recordings , 1978, Circulation research.

[13]  U. Althaus,et al.  [Ventricular arrhythmias in the acute stage of experimental swine myocardial infarct; effect of the beta blocker pindolol and the calcium antagonist Ro 11-1781]. , 1978, Schweizerische medizinische Wochenschrift.

[14]  C W Balke,et al.  Two Periods of Early Ventricular Arrhythmia in the Canine Acute Myocardial Infarction Model , 1979, Circulation.

[15]  D Durrer,et al.  Mechanism and time course of the early electrical changes during acute coronary artery occlusion. An attempt to correlate the early ECG changes in man to the cellular electrophysiology in the pig. , 1980, Chest.

[16]  H. Hirche,et al.  Myocardial extracellular K+ and H+ increase and noradrenaline release as possible cause of early arrhythmias following acute coronary artery occlusion in pigs. , 1980, Journal of molecular and cellular cardiology.

[17]  A. Kleber,et al.  Flow of “Injury” Current and Patterns of Excitation during Early Ventricular Arrhythmias in Acute Regional Myocardial Ischemia in Isolated Porcine and Canine Hearts: Evidence for Two Different Arrhythmogenic Mechanisms , 1980, Circulation research.

[18]  L. Dreifus,et al.  Intramyocardial activation in early ventricular arrhythmias following coronary artery ligation. , 1980, Journal of electrocardiology.

[19]  J. L. Hill,et al.  Effect of Acute Coronary Artery Occlusion on Local Myocardial Extracellular K+ Activity in Swine , 1980, Circulation.

[20]  W. C. Mello.  Influence of intracellular injection of H+ on the electrical coupling in cardiac Purkinje fibres. , 1980 .

[21]  M J Janse,et al.  Electrophysiological changes and ventricular arrhythmias in the early phase of regional myocardial ischemia. , 1981, Circulation research.

[22]  J. Wojtczak.  Influence of cyclic nucleotides on the internal longitudinal resistance and contractures in the normal and hypoxic mammalian cardiac muscle. , 1982, Journal of molecular and cellular cardiology.

[23]  A. Adgey.  Sudden Death, Ventricular Fibrillation, Ventricular Defibrillation — Historical Review and Recent Advances , 1982 .

[24]  R. Weingart,et al.  Ungulate cardiac Purkinje fibres: the influence of intracellular pH on the electrical cell‐to‐cell coupling , 1982, The Journal of physiology.

[25]  Robert Plonsey,et al.  The Four-Electrode Resistivity Technique as Applied to Cardiac Muscle , 1982, IEEE Transactions on Biomedical Engineering.

[26]  W. C. Mello,et al.  Circulation Research an Official Journal of the American Heart Association Brief Reviews Intercellular Communication in Cardiac Muscle Intercellular Junction and the Electrical Coupling of Heart Cells , 2022 .

[27]  A. Adgey,et al.  Acute Phase of Ischemic Heart Disease and Myocardial Infarction , 1982, Developments in Cardiovascular Medicine.

[28]  R. Lazzara,et al.  Regional myocardial blood flow and ventricular arrhythmias following one-stage and two-stage coronary artery occlusion in anesthetized dogs. , 1982, American heart journal.

[29]  R Roberts,et al.  Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients. , 1983, The American journal of cardiology.

[30]  A. Kléber,et al.  Resting Membrane Potential, Extracellular Potassium Activity, and Intracellular Sodium Activity during Acute Global Ischemia in Isolated Perfused Guinea Pig Hearts , 1983, Circulation research.

[31]  R. Riemersma,et al.  Mechanisms of phase 1a and 1b early ventricular arrhythmias during acute myocardial ischemia in the dog. , 1984, The American journal of cardiology.

[32]  W. Penny.  The deleterious effects of myocardial catecholamines on cellular electrophysiology and arrhythmias during ischaemia and reperfusion. , 1984, European heart journal.

[33]  A. Schomig,et al.  Release of Endogenous Catecholamines in the Ischemic Myocardium of the Rat: Part A Locally Mediated Release , 1984, Circulation research.

[34]  T A Johnson,et al.  Effect of serial brief ischemic episodes on extracellular K+, pH, and activation in the pig. , 1985, Circulation.

[35]  M. Spach,et al.  Relating the Sodium Current and Conductance to the Shape of Transmembrane and Extracellular Potentials by Simulation: Effects of Propagation Boundaries , 1985, IEEE Transactions on Biomedical Engineering.

[36]  E. Haber,et al.  The heart and cardiovascular system , 1986 .

[37]  M. Janse,et al.  Relationship between extracellular potassium accumulation and local TQ-segment potential during acute myocardial ischemia in the porcine. , 1987, Journal of molecular and cellular cardiology.

[38]  J. Lowe,et al.  On-line detection of reversible myocardial ischemic injury by measurement of myocardial electrical impedance. , 1987, The Annals of thoracic surgery.

[39]  A. Kleber,et al.  Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle. , 1987, Circulation research.

[40]  A. Noma,et al.  Dependence of junctional conductance on proton, calcium and magnesium ions in cardiac paired cells of guinea‐pig. , 1987, The Journal of physiology.

[41]  J. Francis Heidlage,et al.  Influence of the Passive Anisotropic Properties on Directional Differences in Propagation Following Modification of the Sodium Conductance in Human Atrial Muscle: A Model of Reentry Based on Anisotropic Discontinuous Propagation , 1988, Circulation research.

[42]  M. Janse,et al.  Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. , 1989, Physiological reviews.

[43]  W. Cascio,et al.  Passive electrical properties, mechanical activity, and extracellular potassium in arterially perfused and ischemic rabbit ventricular muscle. Effects of calcium entry blockade or hypocalcemia. , 1990, Circulation research.

[44]  P Schweitzer,et al.  The electrocardiographic diagnosis of acute myocardial infarction in the thrombolytic era. , 1990, American heart journal.

[45]  K. Kamiya,et al.  ATP directly affects junctional conductance between paired ventricular myocytes isolated from guinea pig heart. , 1990, Circulation research.

[46]  L. Gettes,et al.  Fabrication, evaluation, and use of extracellular K+ and H+ ion-selective electrodes. , 1990, The American journal of physiology.

[47]  T. Opthof,et al.  Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. , 1991, Circulation research.

[48]  S. Pogwizd,et al.  Amphipathic lipid metabolites and their relation to arrhythmogenesis in the ischemic heart. , 1991, Journal of molecular and cellular cardiology.

[49]  L. Gettes,et al.  Magnitude and time course of extracellular potassium inhomogeneities during acute ischemia in pigs. Effect of verapamil. , 1991, Circulation.

[50]  A. Kleber,et al.  Propagation of Electrical Activity in Ischemic and Infarcted Myocardium as the Basis of Ventricular Arrhythmias , 1992 .

[51]  M S Spach,et al.  Initiating Reentry: , 1994, Journal of cardiovascular electrophysiology.