Using an isolated working heart model, we studied the effects of
dopamine,
adrenaline, or
noradrenaline pretreatment on
ischemia/reperfusion injury. Hearts from Wistar rats were perfused in the first 20-minute working mode, 15 minutes in Langendorff mode, and in the second 20-minute working mode. Hearts were treated with
dopamine (0.52 and 2.60 mmol/L),
adrenaline (16 and 80 nmol/L), or
noradrenaline (16 and 80 nmol/L) during the second working perfusion, then arrested with
St. Thomas' Hospital cardioplegic solution and subjected to global
ischemia (37 degrees C or 20 degrees C). During reperfusion, recoveries of cardiac function and
creatine kinase leakage were measured. At 37 degrees C,
dopamine and
adrenaline had a harmful effect at both doses;
noradrenaline was harmful at a high dose but beneficial at a low dose. At 20 degrees C,
adrenaline,
dopamine, and
noradrenaline had a harmful effect at high doses but no harmful effect at low doses. To determine the role of beta
adrenergic stimulation before
ischemia, a dose-response study was undertaken with isoprotelenol and
milrinone at 37 degrees C. Combined pretreatment with isoprotelenol and
milrinone accelerated
ischemia/reperfusion injury dose-dependently. Preischemic beta
adrenergic stimulation thus plays a significant role in the deleterious effect of
catecholamine pretreatment at high doses. At low doses, however, the effect of the inotropic agent could be changed depending on ischemic temperature. Our results suggest that
catecholamine should not be given at high doses before
ischemia, regardless of temperature during
ischemia.