Background: Adenosine has been reported to mediate the necrosis-limiting effects of ischemic preconditioning; however, it is unclear how this mediation occurs. The present study was undertaken to test the hypothesis that ischemic preconditioning increases 5'-nucleotidase activity and adenosine release during sustained ischemia and subsequent reperfusion.
Methods and results: After thoracotomy, the left anterior descending coronary artery was cannulated and perfused with blood redirected from the left carotid artery in 32 dogs. Ischemic preconditioning was produced by four cycles in which the coronary artery was occluded and then reperfused for 5 minutes each. After the last cycle of ischemia and reperfusion, the coronary artery was occluded for 40 minutes. This was followed by 120 minutes of reperfusion. In the control group, the coronary artery was occluded for 40 minutes and reperfused for 120 minutes without ischemic preconditioning. The plasma adenosine concentration was measured and blood gases were analyzed in coronary arterial and venous blood samples taken during 120 minutes of reperfusion. Myocardial 5'-nucleotidase activity was measured before and at 40 minutes of sustained ischemia with and without ischemic preconditioning. The adenosine concentration in coronary venous blood during reperfusion was significantly higher in preconditioned hearts than in the control hearts: 1 minute after the onset of reperfusion, 546 +/- 57 versus 244 +/- 41 pmol/ml; 10 minutes after, 308 +/- 30 versus 114 +/- 14 pmol/ml; 30 minutes after, 175 +/- 24 versus 82 +/- 16 pmol/ml, respectively (p < 0.01). Ectosolic and cytosolic 5'-nucleotidase activities increased in both endocardial and epicardial myocardium in the ischemia-preconditioned hearts. Furthermore, 40 minutes of ischemia increased 5'-nucleotidase activity in ischemia-preconditioned hearts more than in control hearts.
Conclusions: Ischemic preconditioning increases adenosine release and 5'-nucleotidase activity during sustained ischemia and subsequent reperfusion.