Adenosine and Dipyridamole Mimic the Effects of Ischemic Preconditioning

Abstract

The effects of preconditioning, adenosine and dipyridamole in protecting the systolic and diastolic alterations of myocardial stunning in rabbit hearts were studied. Isovolumic left ventricular developed pressure (LVDP), and end diastolic pressure (LVEDP) were measured. The time constant of relaxation ( T) was calculated. Isolated rabbit hearts were subjected to 15 min of global ischemia (37°C) followed by 30 min of reperfusion. LVDP and LVEDP stabilized to 55 ± 5% and 320 ± 28% of control values respectively (stunned group) T increased early reperfusion (from 48.2 ± 3.9 to 97.2 ± 10 ms P > 0.05) but returned to control value late in reperfusion. When hearts were preconditioned by a single cycle of 5 min of ischemia LVDP and LVEDP stabilized at 89 ± 3% and 162 ± 34% of presichemic values respectively ( P> 0.05 with respect to stunned group). The change in T was attenuated (62 ± 6ms at 5 min of reperfusion P > 0.05 with respect to stunned group). Hearts treated either with adenosine (800 μg/min) or the nucleoside transport blocker dipyridamole (4 μg/min) previously to the ischemia, recovered their LVDP to 86 ± 1% and 82 ± 3% of preischemic values, respectively ( P > 0.05 with respect to stunned group). Adenosine and dipyridamole also attenuated the increase in LVEDP (195 ± 12% and 195 ± 12% and 197 ± 10% respectively. P > 0.05 with respect to stunned group). The increase in T (56 ± 1ms with adenosine and 66 ± 7ms for dipyridamole) were significantly lower with respect to stunned group value ( P > 0.05) Our data demonstrate that either exogenous adenosine or dipyridamole, can mimic ischemic preconditioning in that systolic and diastolic alterations of stunned rabbit hearts are attenuated.