1005-77 Is Activation of 5′–-Nucleotidase and Following Adenosine Release a Common Pathway for Mediating Ischemic Preconditioning Among Species?

Abstract

There is a rising interest on the subcellular mechanism of cardioprotection afforded by ischemic preconditioning (IP). Adenosine has been reported to play a primary role for preconditioning in dogs, pigs, rabbits but not in rats. Common compounds or mechanisms for preconditioning among species would seem to have some benefits in the clinical settings. In dogs, we reported that an increase in ecto-5′-nucleotidase (5′N) activity is responsible for the infarct size (IS)-1imitation of IP To test the hypothesis that IS-limitation afforded by IP is also attributable to activation of 5′N in rabbits, primary branch of the left coronary artery was occluded for 30 min followed by 3 hrs reperfusion with one time occlusion for 5 min prior to prolonged ischemia in the presence or absence of α , β -methyleneadenosine 5′-diphosphate (AOPCP), a specific inhibitor of 5′N. In the absence of AOPCP, IS in the IP group was smaller than that in the control group (17.1 ± 1.9 vs. 29.7 ± 5.2% of risk area, mean ± SE, n = 5 each, p < 0.05), although the risk area was not different in both groups. IP increased 5′N activity in ischemic area compared with that in non-ischemic area (42.1 ± 5.0 vs. 21.2 ± 1.9 nmol/mg proteinlmin, p < 0.01). When non-hypotensive dose of AOPCP (0.3 mg/kg/min) was infused from the left atrium 15 min before the IP and continued for 60 min after reperfusion, IS-limitation was blunted (IS: 30.2 ± 4.7%). Thus we conclude that increase in 5′-nucleotidase activity is primarily responsible for IS-limitation of IP in rabbits. Activation of 5′-nucleotidase may be a commom pathway for mediating IP both in dogs and rabbits.