Influences of labetalol a combined alpha- and beta-adrenergic blocking agent on the dysrhythmias induced by coronary occlusion and reperfusion.

Abstract

We have previously demonstrated a significant antifibrillatory effect of α-adrenergic blockade during myocardial ischaemia and reperfusion, enhanced α-adrenergic responsivity and increased α1-adrenergic receptors in ischaemic myocardium. β-adrenergic blockade is also antiarrhythmic in ischaemic hearts and may decrease the ultimate area of necrotic tissue after infarction. The present study was performed to assess the relative β- and α-adrenergic blocking potency of labetalol in the chloralose anaesthetised cat and correlate this to its antiarrhythmic efficacy during LAD coronary occlusion for 35 min followed by reperfusion. Based on the dose ratio10 (DR10) for isoprenaline-induced tachycardia (β) and phenylephrine-induced increase in mean systemic arterial pressure (α), labetalol was 3.1 times less potent than d,l-propranolol (β) and 6.5 times less potent than phentolamine (α). Labetalol was found to be 11.5 times more potent as a β-adrenergic blocking agent than as an α-adrenergic blocking agent. Labetalol (1 mg·kg−1) failed significantly to reduce either the number of premature ventricular complexes (PVCs) or incidence of ventricular fibrillation (VF) during occlusion (827± 150 to 852±246 PVCs and 31% to 20% VF) or reperfusion. In contrast, labetalol at 2 mg·kg−1 and 5 mg·kg−1 significantly (P<0.05) reduced the number of PVCs during occlusion (320±94 and 466± 137, respectively) as well as the incidence of VF (9% and 7%, respectively). During, reperfusion, labetalol (5 mg·kg−1) failed to reduce the number of PVCs but abolished mortality due to VF. The antifibrillatory effect of labetalol was not due to alterations in systemic arterial pressure, heart rate, LVEDP, cardiac output, stroke work or total peripheral resistance. Thus, labetalol, an agent well-tolerated clinically, induces profound antiarrhythmic effectiveness during both experimental myocardial ischaemia and reperfusion and may prove to be an effective agent in the prevention and treatment of malignant ventricular dysrhythmia associated with acute myocardial infarction in man.