ALPHA-1-ADRENERGIC RECEPTOR AGONIST-INDUCED PRECONDITIONING IN ISOLATED WORKING RAT HEARTS

The aim of this study was to determine whether pharmacologic precondit ioning, without a short episode of myocardial hypoxia or ischemia, cou ld improve myocardial function after a prolonged period of ischemia. I solated rat hearts were perfused with .01, .1 or 1 mg/L of phenylephri ne for 5 min followed by a 10-min washout period (preconditioning) bef ore the induction of 30 min of normothermic global ischemia and 30 min of reperfusion. Hearts preconditioned with increasing concentrations of phenylephrine (an alpha-1 adrenergic receptor agonist) produced a r eduction in the incidence of reperfusion-induced ventricular fibrillat ion (VF) and ventricular tachycardia (VT). Preconditioning of the hear ts with the highest dose of phenylephrine (1.0 mg/L), after 30 min of ischemia, reduced the incidence of reperfusion-induced VF and VT from their nonpreconditioned control values of 87% and 100% to 33% (P < .05 ) and 50% (P < .05), respectively. After 30 min of ischemia, the recov ery of myocardial function was significantly improved in phenylephrine -preconditioned groups. Thus, .1 and 1.0 mg/L of phenylephrine increas ed aortic flow from its nonpreconditioned control value of 10.8 +/- .9 ml/min to 22.4 +/- 2.4 ml/min (P < .05) and 26.5 +/- 1.5 ml/min (P < .05), respectively. Phenylephrine (1.0 mg/L) preconditioning significa ntly reduced ischemia/ reperfusion-induced tissue Na+ and Ca2+ gains a nd prevented K+ and Mg2+ loss measured by an atomic absorption spectro photometer. Our results show that alpha-1 adrenergic stimulation (prec onditioning) can prevent postischemic abnormalities in intracellular i ons, reperfusion arrhythmias, and contractile function without the inh ibition of O-2 delivery.