Alpha2-Adrenergic stimulation is protective against ischemia-reperfusion-induced ventricular arrhythmias in vivo

We previously reported that alpha2-adrenergic receptor (alpha2--AR) stimulation in Purkinje fibers in vitro prolongs action potential duration and suppresses beta-adrenergic-induced delayed after depolarizations and sustained triggered activities. We examined the effects of alpha-AR stimulation on reperfusion-induced ventricular arrhythmias [ventricular tachycardia/ventricular fibrillation (VT/VF)] in vivo. Arterial blood pressure, heart rate, surface electrocardiogram, and renal sympathetic nerve activities were recorded simultaneously in Sprague-Dawley rats. The incidence of VT/VF was 87.5% for controls, 50% for the beta-blocker group, 72% for the alpha1-blocker group, and 12.5% for the alpha1+beta-blockers (unopposed alpha2-adrenergic activation). Direct alpha-AR stimulation with UK-14304 also prevented VT/VF. These effects were reversed by the 2-adrenergic antagonist yohimbine. Increases in renal sympathetic nerve activity were associated with left anterior descending coronary artery ligation and reperfusion (33 +\- 1.5 and 62 +\- 1.7% over baseline, respectively) in controls. Similar patterns were observed among all experimental groups irrespective of the incidence of VT/VF on reperfusion. We conclude that alpha2-AR stimulation has a potent antiarrhythmic effect on ischemia-reperfusion-induced VT/VF in vivo and that this effect is not centrally mediated.