Kristina Epstein

Electrophysiologic consequences of chronic experimentally induced left ventricular pressure overload

Cardiac electrophysiologic alterations were evaluated 1 to 8 months after partial supracoronary aortic constriction in cats. This procedure induced left ventricular systolic hypertension and hypertrophy with marked connective tissue infiltration. In situ, premature ventricular complexes were observed during or after vagal slowing of sinus rate in 8 (26%) of the 31 experimental animals, while an additional 3 of the 31 developed ventricular fibrillation. No arrhythmias were recorded in 31 normal or 7 sham-operated cats. In vitro, 29% of the left ventricular preparations from cats with pressure overload and 5% from control cats showed spontaneous ectopic activity. During stimulation at cycle lengths of 800 to 1,000 ms, multiple site impalements of subendocardial muscle cells within fibrotic regions revealed heterogeneous electrical abnormalities. These included short action potential duration, low amplitude action potentials generated from low resting potentials, split upstrokes and electrically silent areas. Impalements in nonfibrotic areas of the left ventricle showed prolongation of muscle action potential duration. Long-term disturbances in cellular electrophysiologic properties may favor the development of arrhythmias and thereby contribute to sudden cardiac death in left ventricular hypertension and hypertrophy.

Dissimilarities in the electrophysiological abnormalities of lateral border and central infarct zone cells after healing of myocardial infarction in cats

We studied the characteristics of an electrophysiological border zone detected after healing of experimental myocardial infarction in cats. Thirty-two isolated left ventricles were studied in tissue bath 2–7 months after distal left coronary artery ligation. Action potentials were recorded from endocardial ventricular muscle cells in normal, lateral border and central infarct zones. Action potential duration was prolonged in central infarct zone cells, while action potentials of lateral border zone cells had the shortest duration. Ventricular muscle cells in the border zone also had lower resting potential, action potential amplitude and Vmax. Slowly rising action potentials (Vmax ≪ 20 V/ sec) were noted in central infarct zone cells, but more consistently in border zone cells. Functional refractory period of cells in central infarct zone was significantly longer than that recorded from border and normal zone cells. Post-repolarization refractoriness occurred in the majority of border zone cells. Failure of a border zone cell to respond to a premature stimulus during repetitive activity was observed in ten of the 22 preparations in which repetitive activity could be induced. Furthermore, when the coupling interval between driving and premature stimuli was shortened, border zone cells were first to fail to be excited by the premature stimulus. These data indicate that conduction was impaired in the border zone, whereas normal conduction was still possible in central infarct and normal areas. The electrophysiological abnormalities in the endocardial lateral border zone cells of the healed myocardial infarction appear to be the most severe, and the border zone may play an important role in chronic electrophysiological instability observed both in situ and in vitro.

Electrophysiological effects or procainamide in acute and healed experimental ischemic injury of cat myocardium.

We studied the effects of a membrane-active antiarrhythmic agent, procainamide (PA), on cellular electrophysiological consequences of ischemic injury to cat ventricular muscle. The left ventricles of 90- to 120-minute acute myocardial infarctions (AMI) (n = 14), and 2- to 4-month healed myocardial infarctions (HMI) (n = 17), were studied by microelectrode techniques in isolated tissue bath. Control action potential duration at 90% repolarization (APD90) recorded from ventricular muscle cells in AMI areas were short (114 ± 4 msec) compared to recordings from cells in normal areas (136 ± 6 msec) (P < 0.001). In contrast, APD90 of cells surviving ischemia in HMI preparations were longer than normals (159 ± 5 vs. 140 ± 5 msec, P < 0.001). After 60 minutes of exposure to PA, the APD90 of all cells was prolonged, but the absolute and relative magnitudes of prolongation were greater in AMI cells (mean = +40 msec, +35%), than in HMI cells (mean = +19 msec, +13%), P < 0.001. The prolongation of APD90 of normal cells was intermediate. Local refractory period changes paralleled APD90 changes. In seven additional HMI preparations, sustained ventricular activity was induced by premature stimulation. APD90 of HMI cells prolonged less than APD90 of normal cells during exposure to PA in these preparations, and decreased differences of APD90 between normal and HMI cells was associated with loss of inducibility of sustained ventricular activity. The effect of tetrodotoxin (TTX) was compared to the effect of PA in four HMI preparations to determine whether impaired delivery of test substances caused only an apparent decreased responsiveness to PA in HMI zones. TTX caused nearly identical prolongations of conduction times in HMI zones and normal zones, whereas PA caused different effects on APD90 in the two zones. In conclusion, PA alters the time course of repolarization of AMI cells more than that of HMI cells, decreasing the dispersion of repolarization in a given AMI or HMI preparation. The decreased dispersion correlated with loss of ability to induce sustained ventricular activity. Finally, the decreased responsiveness of HMI cells to PA does not appear to be due to impaired delivery to cell membranes, but, rather, appears to be a membrane difference persisting in cells which have survived ischemic injury.

Electrophysiologic Effects of Verapamil on Cells Bordering Healed Myocardial Infarction in the Cat

Abstract Verapamil (1 μg/ml) completely abolished a population of markedly depressed action potentials of cells (BZ-1) in border zones around healed infarcts. Even at higher concentrations, verapamil had no such inhibitory effect on other border zone cells (BZ-2), normal and central infarct zones cells. BZ-1 cells demonstrated a severely depressed V max (<20 V/sec), accompanied by partial depolarization, while BZ-2 cells were characterized by abbreviated duration. Verapamil only significantly depressed V max of BZ-1 cells. Action potential amplitude and action potential duration at 50% repolarization of all cells were abbreviated by verapamil. These results indicate slow inward currents may be involved in the genesis of action potentials in BZ-1 cells.

Early electrophysiologic and anatomic alterations in cat ventricular muscle after coronary artery ligation

The effect of coronary artery ligation on electrophysiologic properties of cat ventricular muscle cells was studied. Depression of resting potential, action potential rate of rise and amplitude was observed in infarcted cells, 30 min to 5 days after ligation. Action potential duration was markedly shortened in acute stages (30-120 min) but gradually lengthened to above control by 48 h. Anatomic sequelae included oedema, loss of fibre striation and cellular necrosis.

Regional sensitivity to verapamil in ventricular myocardium

The effects of verapamil (0.1-4.0 micrograms/ml) on transmembrane action potential configuration was examined in various regions of the normal cat left ventricular endocardium. Surface electrograms showed that the sequence of activation of anterior papillary muscle fibers was from the base of the muscle to its apex, while overlying Purkinje fibers were activated in the opposite direction. Action potential duration in basal muscle fibers was relatively unaffected by verapamil, while cells at the tip of the papillary muscle showed increased slope in phase 2 and a more rapid rate of early repolarization. Regional sensitivity to verapamil may reflect disparate patterns of endocardial activation, and could influence the effectiveness of the drug against ventricular arrhythmias.