Possible mechanisms of ventricular arrhythmias elicited by ischemia followed by reperfusion. Studies on isolated canine ventricular tissues.

Abstract

The purpose of this study was to develop an isolated tissue model in which arrhythmic activity could be generated in response to conditions encountered in ischemia followed by reperfusion, and in which intracellular recordings could be used to identify and study arrhythmogenic mechanisms. Isolated canine Purkinje fiber-papillary muscle preparations were superfused with modified Tyrode's solutions. Tissues were exposed to conditions observed in ischemia (hypoxia, acidosis, elevated lactate, zero substrate for 40 minutes). Superfusion with Tyrode's solution of "normal" composition was then reinstituted. Transmembrane recordings from Purkinje and muscle tissues were made, using standard microelectrode techniques. Ischemic conditions caused loss of membrane potential, shortened action potentials, depressed excitability, and progressive bidirectional conduction block between muscle and Purkinje tissues. Spontaneous activity, probably reentrant in origin, was observed. Return to nonischemic conditions resulted in a multiphasic sequence of responses in Purkinje fibers: prompt hyperpolarization, progressive depolarization to unresponsiveness, and final repolarization to control. The depolarization phase was accompanied by oscillatory afterpotentials which initiated extrasystoles. Final repolarization included a phase of automaticity at low membrane potentials, during which Purkinje tissue functioned as a parasystolic focus. Elevation of potassium concentration to 10 mM during the ischemic period did not alter the sequence of electrophysiological events during ischemic conditions or upon reperfusion. This study demonstrates that ischemia followed by reperfusion elicits an orderly sequence of electrophysiological events which may constitute important mechanisms of arrhythmia in vivo.

Protection of rat atrial myocardium against electrical, mechanical and structural aspects of injury caused by exposure in vitro to conditions of simulated ischaemia

“…The superfusate was then changed to one of abnormal composition, simulating the extracellular fluid of ischaemic muscle, as suggested by Ferrier et al (1985). This fluid contained KCl 7mM and sodium lactate 20 mm, was made up without added glucose, and had a pH of 6.4 produced by reduction of the NaHCO3 concentration to 4mM.…”

“…In SI of cardiac muscle in vitro, conduction velocity (CV) of action potentials is reduced, as are both action potential duration and refractory periods (Ferrier et al, 1985;Northover, 1987). These changes probably constitute the electrical basis for at least some of the disturbances of rhythm that characterize myocardial ischaemia in vivo (Northover, 1986).…”

Selective IK blockade as an antiarrhythmic mechanism: effects of UK66,914 on ischaemia and reperfusion arrhythmias in rat and rabbit hearts

“…at 10 min after the onset of ischaemia). However, since reperfusion causes rapid washout of K+ from the extracellular space (Watanabe et al, 1988) and rapid hyperpolarization (Ferrier et al, 1985) then QT values during early reperfusion (which we cannot measure) may be better reflected by equivalent values during early ischaemia (e.g. after 10 min at which time extracellular K+ is less elevated ;Hirche et al, 1980) than values at 29 min (when K+ values reach as much as 30 mM; Hirche et al, 1980).…”

Antiarrhythmic Efficacy of Dipyridamole in Treatment of Reperfusion Arrhythmias

“…In contrast, the latter was caused by increased ventricular automaticity and associated with a low frequency of Vfib. 26 On the other hand, Ferrier et al 5 reported that in isolated tissue preparation, DADs and triggered rhythms occurred during conditions that mimicked reperfusion after a 40-minute ischemic episode. Subsequently, this mechanism has also attracted considerable attention as the underlying mechanism of reperfusion arrhythmias, although this has not been demonstrated clinically in patients who have undergone reperfusion therapy because of AMI.…”

“…4,16,26 In contrast, VT is caused by either reentrant or nonreentrant mechanisms and in some cases by triggered activity as a result of DAD. 4,5 However, the reperfusion arrhythmias found in the clinical setting may differ from those observed in experimental models, because factors such as lesion location, collateral flow grade, time to reperfusion, and coronary flow volume can vary. Even among clinical studies, varied incidence of reperfusion arrhythmias has been demonstrated.…”