EFFECT OF ADENOSINE-DEAMINASE INHIBITION WITH PENTOSTATIN ON MYOCARDIAL STUNNING IN DOGS

Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine dea minase and has been demonstrated to augment endogenous adenosine level s during regional and global myocardial ischemia. Based on the rationa le that increasing endogenous adenosine during ischemia may be cardiop rotective, the objective of this study was to determine if adenosine d eaminase inhibition with pentostatin could improve postischemic contra ctile dysfunction (stunning) in open-chest anesthetized dogs. All anim als underwent 15 min of coronary occlusion followed by 3 h of reperfus ion preceded by an intravenous bolus of either 0.2 mg/kg of pentostati n (n = 8) or saline (n = 7). Sonomicrometers were placed in the ischem ic area and were used to measure systolic wall thickening before, duri ng, and after occlusion of the left anterior descending artery. Myocar dial blood flow was measured with tracer labeled microspheres at basel ine, 10 min of occlusion and at 1 h of reperfusion. Both groups were e qually dyskinetic during occlusion (-21 +/- 5 % of baseline thickening in the controls and -28 +/- 8 % in the pentostatin group). The pentos tatin group, however, demonstrated better contractile function at all time points during reperfusion, which was significantly different from the control group at 3 h of reperfusion. The improvement in regional function in the pentostatin group was not due to significant dispariti es in hemodynamic variables, size of the region at risk, or in collate ral blood flow. These results indicate that pentostatin can ameliorate the severity of myocardial stunning, an effect we propose is due to i ncreasing endogenous levels of adenosine during the ischemic interval. Although significant improvement was detected with pentostatin, the i mprovement was modest compared to controls, suggesting that the utilit y of inhibiting adenosine deaminase to modify regional mechanical stun ning is limited.