Effect of preischemic catecholamine treatment on ischemia-reperfusion injury of the myocardium: subtype, dose, and temperature dependency.

Abstract

Preischemic adrenergic stimulation may affect postischemic cardiac function. Using an isolated working heart model, we investigated the effects of preischemic catecholamine treatment on postischemic recovery. Hearts from Wistar rats were perfused in working mode for 20 min, in Langendorff mode for 15 min, and again in working mode for 20 min (W2). Hearts were treated with isoproterenol (8.0 and 40.0 nmol/L), phenylephrine (0.06, 0.30, and 1.50 micromol/L), or epinephrine (16 and 80 nmol/L) during the W2 period and then arrested with St Thomas' Hospital cardioplegic solution (STH) and subjected to global ischemia (37 degrees C or 20 degrees C), followed by reperfusion. At 37 degrees C, isoproterenol had a beneficial effect at the lower dose but a harmful effect at the higher dose; phenylephrine and epinephrine had a harmful effect at all doses. At 20 degrees C, isoproterenol and epinephrine had a harmful effect at a high dose; phenylephrine had no harmful effect at any dose. In a separate study, the influence of calcium modulators (diltiazem and ryanodine, added in the STH) on the catecholamine effect was investigated. The harmful effect of preischemic treatment with isoproterenol (24.0 nmol/L) or phenylephrine (0.9 micromol/L) was abolished by the calcium modulators. Thus, preischemic beta-adrenergic or alpha + beta-adrenergic stimulation has a deleterious effect on postischemic recovery of the myocardium. The effect could be altered depending on the subtype and dose of catecholamine and the ischemic temperature. Intracellular calcium movement could be involved in the mechanism responsible for the harmful effect of preischemic catecholamine treatment.