Effects of some components of ischemia on electrical activity and reentry in the canine ventricular conducting system.

Abstract

We used intracellular microelectrodes to study the electrophysiological effects of combinations of components of ischemia and their relation to the occurrence of ventricular arrhythmias in the specialized conducting system of isolated canine right ventricles. The middle area of the free wall was exposed to various test solutions in the center compartment of a three-chambered bath; the base and apex of the preparation were superfused with normal Tyrode's solution in the outer control compartments. Hypoxia (Po2 40 mm Hg), lactic acidosis (pH 6.5), and orciprenaline (10(-6) M), either alone or combined, failed to affect the action potential amplitude or the conduction velocity of the subendocardial fibers, and no arrhythmias occurred. The action potential duration and the effective refractory period were markedly prolonged by lactic acidosis. Exposure of the test regions to 15 mM K+ plus orciprenaline resulted in marked decreases in action potential amplitude and conduction velocity. Abnormalities of impulse transmission through the depressed area included high degrees of rate-dependent block, one-way block, warming-up phenomenon, and the Wenckebach phenomenon. Such conditions regularly provoked the appearance of single, sustained, or concealed reentrant depolarizations. The combined effects of hypoxia, 15 mM K+, and orciprenaline resulted in further depression of the already depressed action potential in the depolarized fibers. Our results indicate that regional increases of extracellular K+ may be the predominant factor of the components of ischemia we studied which facilitates the initiation of reentrant arrhythmias.

Role of some components of ischemia in the genesis of spontaneous ventricular arrhythmias

“…lar Purkinje fibers providing no evidence of increased focal automaticity. Furthermore, in the presence of regional hypoxia and acidosis no reentrant tachycardia could be induced despite marked alterations of the local refractory periods (19). The important common fa~ in both hypoxia and acidosis was that they failed to cause a conduction delay confirminl earlier results (1, 3, 10, 21).…”

“…Hypotheses concerning possible characteristics of electrical activity in ischemic or infarcting myocardium has been derived from results of electrophysiological studies on isolated ventricular tissues exposed to such substances that may be present in the ischemic environment (1,3,5,10,20). Previous results obtained from an in-vitro model of regional ischemia using a three-chambered bath have indicated that hypoxia, acidosis or catecholamines, either alone or combined, did not provoke ventricular arrhythmias and that regional increase in extracellular K § was the predominant arrhythmogenic factor (19).…”

Effects of verapamil on ischemia-induced changes in extracellular K+, pH, and local activation in the pig.

“…Various drugs, including the calcium channel-blocking agents, are capable of suppressing these arrhythmias.14 15 Although the mechanism(s) by which the calcium-blocking agents suppress arrhythmias remains uncertain, several potentially antiarrhythmic effects of various members of this class of agents have been demonstrated in the setting of acute ischemia. These include (1) a decrease in the size of an experimental infarct zone,16 (2) a lessening in the delay in local activation, '7-20 (3) metabolic protection of the ischemic tissues,2' 24 and (4) a decrease in the rate of [K']e accumulation.25 27 However, the effects of calcium blockers on the metabolic, electrical, and ionic changes during ischemia have not been correlated in the same experimental preparation. Nor have these effects been demonstrated in an experimental preparation with low collateral flow, such as the pig.28 '29 We have recently reported that serial 10 min coronary occlusions in the swine heart in situ provide a useful method of studying the ischemia-induced changes in myocardial [K] Miniature K'-sensitive and H+-sensitive plunge electrodes, modified from earlier designs,10 were fashioned by methods described in detail elsewhere.…”

Calmodulin kinase II initiates arrhythmogenicity during metabolic acidification in murine hearts

“…Acidification is an early and important biochemical change associated with acute myocardial ischaemia (Elliott et al 1992, Vandenberg et al 1993) and may contribute importantly to the enhanced risks of potentially life-threatening arrhythmias in such situations (Senges et al 1979, Luqman et al 2007). The mechanisms underlying arrhythmogenicity in metabolic acidification have therefore attracted extensive study (Orchard & Cingolani 1994).…”