Activation of adenosine receptors before ischemia enhances tolerance against myocardial stunning in the rabbit heart

Objectives.This study examined whether stimulation of adenosine receptors before ischemia enhances myocardial resistance to stunning in vivo.Background.We previously demonstrated the attenuation of myocardial stunning by ischemic preconditioning through adenosine receptor activation in rabbits.Methods.1) To confirm the efficacy of an intravenous infusion of adenosine to stimulate adenosine receptors in the heart, we assessed the effect of an adenosine infusion on the inotropic response to an isoproterenol challenge. 2) Myocardial stunning was induced by 10 min of coronary occlusion and reperfusion. The regional thickening fraction was monitored by an epicardial Doppler sensor. Rabbits were pretreated with either no drug (control group), adenosine, 8-phenyltheophylline or a combination of 8-phenyltheophylline plus adenosine.Results.An intravenous infusion of adenosine at 0.15 mg/kg body weight per min attenuated by 50% the elevation of left ventricular dP/dtmaxby isoproterenol (0.075 μg/kg per min). The same dose of adenosine infused for 15 min before ischemia significantly improved the postischemic recovery of the thickening fraction, and the thickening fraction at 30 min reperfusion was 76.8 ± 3.3% (mean ± SE) of the baseline value, which was significantly higher than the control value (42.9 ± 4.5%). The relation between thickening fraction and systolic left ventricular pressure after reperfusion was shifted toward higher thickening fraction by adenosine. This beneficial effect of adenosine was not detected in rabbits given 8-phenyltheophylline before adenosine, and 8-phenyltheophylline-treated rabbits showed a time course of thickening fraction similar to that in the control group.Conclusions.An intravenous infusion of adenosine is capable of protecting rabbit hearts against stunning through adenosine receptor activation