An evaluation of automaticity and triggered activity in the canine heart one to four days after myocardial infarction.

Abstract

Both abnormal automaticity and triggered activity induced by delayed afterdepolarizations have been proposed as the primary mechanism for ventricular tachycardia (VT) occurring in dogs 24 hr after ligation of the left anterior descending coronary artery. Because of this controversy, we studied the effects of ventricular pacing and therapeutic concentrations of lidocaine and ethmozin on sustained rhythmic activity of isolated subendocardial preparations excised from the infarct, and on VT in conscious dogs. There were differences in the sustained rhythmic activity cycle length of isolated preparations and the VT cycle length that were attributable to the absence of sympathetic input in the former and its presence in the latter. In isolated tissues, pacing for 1 or 10 beats reset the sustained rhythmic activity and pacing for 1 min induced overdrive suppression. Lidocaine (5 gtg/ml) had no effect on sustained rhythmic activity but ethmozin (2 g.g/ml) suppressed it. Delayed afterdepolarizations occurred but appeared to be induced by pacing or by the hyperpolarization associated with recovery. Although delayed afterdepolarizations were infrequent at 24 hr, their frequency increased with the hyperpolarization of the membrane that occurred at 48 to 96 hr after infarction. Delayed afterdepolarizations also occurred more readily when superfusate temperature was lowered. In conscious dogs, pacing the VT for 1 or 10 beats or 1 min had no effect. Lidocaine (2 to 10 ,Lg/ml) did not affect the VT but ethmozin (2 to 5 gg/ml) increased VT cycle length significantly. Pacing for 1 min in the presence of ethmozin, but not lidocaine, converted VT to sinus rhythm. Our results suggest that although delayed afterdepolarizations occur at 24 hr after infarction in the standard Harris preparation, they are most readily seen as an accompaniment of hyperpolarization, pacing, or lowering of bath temperature. The predominant rhythm at 24 hr appears to be automatic. Circulation 71, No. 6, 1224-1236, 1985 PREVIOUS STUDIES 14have shown that the origin of the ventricular tachycardia (VT) that occurs 24 hr after ligation of the left anterior descending coronary artery in the dog is in the subendocardial zone of the infarct. These studies attributed the VT to automaticity of depressed subendocardial Purkinje fibers that survived the infarct, although the possibility of reentry was considered.2' 3 Triggered activity resulting from delayed afterdepolarizations has also been noted in the 24 hr infarct, and From the

The antiarrhythmic efficacy of amiodarone and desethylamiodarone, alone and in combination, in dogs with acute myocardial infarction.

“…26 The ability of fast-channel blockers to suppress arrhythmias in vivo 24 hr after infarction in dogs27 is presumably related to their capacity to suppress automaticity occurring at reduced levels of transmembrane potential. 22 The relatively greater antiarrhythmic potency of desethylamiodarone compared with amiodarone in the current experiments is therefore consistent with our previous observations suggesting that the metabolite is a more potent sodium-channel blocker in vivo than the parent compound.8' 9 The slowing of the rate of ventricular tachycardia observed along with arrhythmia suppression in the current experiments is compatible with an automatic mechanism of arrhythmia. The extent to which the present observations can be extrapolated to the antiarrhythmic effects of amiodarone and its metabolite on arrhythmias due to other mechanisms, such as reentry, remains to be determined.…”

The effects of doxorubicin on ventricular tachycardia.

“…Cardiac pacing was effected with a WPI stimulator, and electrocardiograms and electrograms were recorded with a strip-chart recorder and previously described techniques. 12 At the start of each study, all hearts were paced via the atrial and ventricular plaques by the following protocol. Initially a drive cycle length 5% shorter than that of the spontaneous rhythm was used, followed by cycle lengths of 300, 250, and LABORATORY INVESTIGATION-ELECTROPHYSIOLOGY 200 msec for 1 min each.…”

“…12 Although it has been suggested that triggered activity might be the cause of such arrhythmias,20 recent studies have suggested that infarct-induced triggered activity is seen only in special instances; for example, in microelectrode studies of 24 hr infarcts at low temperature (360 C rather than the 390 C usually seen in the normal dog8 ' 14), in instances in which hyperpolarization of the membrane is occurring, 12 or in instances in which the infarct (or the tissue sample studied) is small.2' In the intact animal after myocardial infarction, a response to pacing consistent with triggered activity (i.e., a decrease in the escape interval and/or an increase in ventricular tachycardia rate after overdrive pacing) usually is not seen at 24 hr (except in the presence of small infarcts) and is more frequent at 48 to 96 hr, at which time the infarct has begun to heal, and the membrane to hyperpolarize. 12 It was because of the above information that we did not expect doxorubicin to suppress ventricular tachycardia occurring 24 hr after infarction.…”

Effects of caffeine and ryanodine on delayed afterdepolarizations and sustained rhythmic activity in 1-day-old myocardial infarction in the dog.

“…Our study suggests that one need not invoke a separate, intrinsically oscillating mechanism, such as abnormal automaticity, to explain the existence of sustained in comparison with nonsustained rhythms in the same heart or isolated preparation 1 day after infarction. 6 Some investigators67 have used a matrix of drugs that have different effects on the different arrhythmogenic mechanisms to identify the electrophysiological mechanism of sustained rhythmic activity in canine endocardial preparations 1 day after infarction. This approach could be limited by the fact that most drugs act by more than one mechanism and that different concentrations of drugs can have varying effects.…”