The anti-arrhythmic effects of myocardial ischaemia. Relation to reperfusion arrhythmias?
Ventricular tachycardia was induced in the intact non-ischaemic pig heart by intramyocardial or intracoronary infusions of noradrenaline or N6, O2'-dibutyryl-cAMP. The chemically induced tachycardia was consistently stopped within 10 to 30 s by occluding the coronary artery supplying the infusion area. This ischaemic effect was readily reversed by coronary reperfusion, with ventricular tachycardia resuming within seconds after release of the occlusion. In contrast to the immediate effect of myocardial ischaemia, it took several minutes for the tachycardia to cease after the infusion of arrhythmogenic compounds was stopped. Pacing experiments showed that the effect of myocardial ischaemia on ventricular tachycardia was probably not due to a conduction block. The anti-arrhythmic property of myocardial ischaemia was separate from its known effect of decreasing the ventricular fibrillation threshold for electrical stimulation. The increased vulnerability of the acutely ischaemic myocardium to fibrillation was apparent in experiments in which ectopic activity was induced in the non-ischaemic part of the myocardium. In these experiments ventricular fibrillation consistently ensued within 6 min following distal occlusion of the anterior descending coronary artery. By contrast, ventricular fibrillation was not precipitated by coronary artery occlusion or local infusion of arrhythmogenic compounds alone. Cyclic AMP was shown to accumulate in ischaemic myocardium. An association existed between cAMP accumulation and the intensity of early ischaemic arrhythmias as well as reperfusion arrhythmias. The highest incidence of ventricular fibrillation was found during reperfusion, at peak myocardial cAMP levels. These findings suggest: (1) Noradrenaline and dibutyryl-cAMP exert arrhythmogenic effects preferentially in the intact, non-ischaemic myocardium, the effects being attenuated in ischaemic myocardium by a paradoxical anti-arrhythmic effect of ischaemia. (2) In the acutely ischaemic heart, ventricular fibrillation may be precipitated by the emergence of ectopic activity outside the ischaemic area. (3) Arrhythmias and fibrillation occurring early after reperfusion may be caused by unmasking the effects of excitants (eg, noradrenaline or cAMP) arising during the antecedent period of ischaemia.
Podzuweit
T
T
Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Federal Republic of Germany.
Binz
K H
KH
Nennstiel
P
P
Flaig
W
W
D000818:Animals; D003994:Bucladesine; D002304:Cardiac Pacing, Artificial; D003250:Constriction; D003327:Coronary Disease / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000378:metabolism; D006352:Heart Ventricles; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine; D013552:Swine; D013610:Tachycardia / Q000139:chemically induced / Q000150:complications*
D003994:Bucladesine; D000242:Cyclic AMP; D009638:Norepinephrine