Verapamil prevents slowing of transmural conduction and suppresses arrhythmias in an isolated guinea pig ventricular model of ischemia and reperfusion.

Abstract

Transmembrane electrical activity was recorded from endocardium and epicardium of isolated segments of guinea pig right ventricular free walls. An electrocardiogram was recorded by electrodes at opposite ends of the tissue bath. Endocardium was stimulated. Tissues were exposed to "ischemic" conditions (e.g., acidosis, hyperkalemia, hypoxia, and lactate) for 15 minutes and then were reperfused with "normal" Tyrode's solution. Arrhythmias with characteristics of transmural reentry occurred in ischemic conditions and early reperfusion in 30% and 70%o of 20 control hearts, respectively. Arrhythmias were associated with prolongation of transmural conduction time (CT) and abbreviation of endocardial effective refractory period. Verapamil significantly suppressed reperfusion arrhythmias at 0.1-1.0 ,&M but not at 3.0 jiM. Verapamil also significantly decreased the incidence of arrhythmias during ischemic conditions at 0.5 ,uM but significantly promoted ischemic arrhythmias at 3.0 jiM. Action potential duration and effective refractory period were not altered by verapamil during ischemic conditions or reperfusion. However, at 0.1-1.0 ,iM, verapamil prevented or attenuated prolongation of transmural CT by ischemic conditions and reperfusion. Transmural CT was further prolonged at 3 ,uM verapamil. In epicardial slices, 1 ,uM verapamil shortened CT transverse to fiber orientation during reperfusion but had no effect on longitudinal CT. Our results indicate that verapamil may suppress arrhythmias through differential effects on CT transverse and longitudinal to fiber orientation in anisotropic ventricular tissues and thus by specifically improving transmural conduction. (Circulation Research 1992;70:651-659)

Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea‐pig heart

“…Local repolarization times (determined at S 1 –S 1 = 550 ms) were calculated as a sum of activation latency and APD 90 . The LV transmural conduction time was found as a difference between epicardial and endocardial activation latency times, as determined previously in perfused rodent ventricles (Li & Ferrier , Sabir et al . , Osadchii & Olesen ).…”

Differential Effects of Sarcolemmal and Mitochondrial KATP Channels Activated by 17β-Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts

“…Opening of sar-K ATP channels enhances the shortening of the action potential duration by accelerating repolarization, which would inhibit calcium entry into the cells (Jovanovic et al, 1999). Because reperfusion arrhythmia may occur secondary to calcium overload (Li and Ferrier, 1992), activation of sar-K ATP channels may protect against arrhythmias by attenuating calcium overload during reperfusion.…”

Extracellular proton depression of peak and late Na+ current in the canine left ventricle

“…This loss of excitability tends to occur in ventricular epicardial (Epi) versus endocardial (Endo) tissues (12,15,21,24). Several mechanisms for this Epi versus Endo tissue response have been described.…”