Cellular electrophysiology of human myocardial infarction. 1. Abnormalities of cellular activation.

Abstract

SUMMARY Ventricular tissues were obtained at the time of operation from 12 patients who underwent aneurysmectomy or mitral valve replacement. The electrophysiologic characteristics of these tissues were determined in a tissue bath using microelectrodes. Normal-appearing action potentials were recorded from surviving Purkinje fibers and ventricular muscle cells within infarcted ventricular tissues. Normal muscle action potential recordings from infarcted tissues were similar to action potentials from noninfarcted papillary muscles, except that the duration of the action potential was significantly longer in the former. In other areas slow response potentials were recorded. These action potentials conducted slowly and were eliminated by verapamil. We observed verapamil-sensitive slow response automaticity, but this did not correlate with ventricular tachycardias, present in three patients. Variable amplitude responses arising from normal resting potentials and characterized by stimulus intensity-dependent changes in action potential amplitude were recorded in tissues from two patients. These potentials had many characteristics similar to the slow response, but were not eliminated by verapamil. We also saw inexcitable cells with both normal and abnormal resting potentials. The heterogeneous electrophysiologic characteristics of these tissues provide a likely substrate for arrhythmias and may be the source of the ectopic ventricular rhythms observed in these patients. cardium 1-60 months after acute myocardial infarction. The observations indicate that both Purkinje fibers and muscle cells survive. We also document persistent electrophysiologic abnormalities in surviving cells of tissues obtained as late as 60 months after infarction. MethodsSpecimens of human ventricular tissue were obtained from 12 patients at the time of cardiac surgery. The patients ranged in age from 37-68 years. Aneurysmectomy was performed for intractable heart failure or ventricular tachycardia. Mitral valve replacement was performed for severe mitral regurgitation. Before surgery, all patients had some degree of chronic congestive heart failure (table 1). Three of the 12 patients had chronic sustained ventricular tachycardia. No patients had evidence of digitalis toxicity. Cardioactive drugs were discontinued at least 24 hours before operation in nine of 12 patients without ventricular tachycardia, but were continued in the three patients with arrhythmia to the time of surgery. Morphine and halothane were used as anesthetics.The tissues were resected promptly at the initiation of cardiopulmonary bypass and were placed in continuously oxygenated, cooled (20-21°C) Tyrode

Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity.

“…Note that the VPC, and VPC, intervals gradually shorten as the driving cycle length (CL) progressively decreases. fast sodium channel rather than the calcium-dependent slow channel response (45,46) in our group I patients.…”

Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs.

“…The effects of verapamil and diltiazem on the mechanical alternans are summarized in figure 6. Verapamil attenuated the 34 We have previously shown that the STA is a correlative to the alternation in phase 2 of a membrane action potential, and that STA is not always accompanied by the alternation of the duration of the action potential.5 Therefore, it seems that the alternation in the calcium flow during the phase 2 may be involved in STA. In this study, verapamil and diltiazem prominently attenuated the degree of STA.…”

Alterations in endocardial activation of the canine papillary muscle early and late after myocardial infarction.

“…The loss of cells and cell-to-cell connection that occurs in chronic infarction has been associated with both generalized and local abnormalities of activation in other preparations.20 22 The changes in P layer activation noted in the present study, specifically generalized slowing, local conduction block, and fragmentation as well as electrotonic distortion of action potentials, are strikingly similar qualitatively to abnormalities noted in canine epicardial muscle overlying a chronic infarction20-22 and in isolated human tissue. 23,[36][37][38] It seems clear from our late studies of P and VM activation that the P layer in ischemic regions remains quite viable electrophysiologically, despite complete loss of the underlying VM layer. Despite rather modest generalized slowing, 1:1 conduction was routinely maintained even to sites deep within the ischemic zone.…”