Pharmacologic stimulation of adenosine A(2) receptor supplants ischemic preconditioning in providing ischemic tolerance in rat livers

Background. Ischemic preconditioning (IPC) is a promising strategy for conf erring ischemic tolerance. We confirmed the acquisition of ischemic toleran ce in the liver immediately after IPC and the role of adenosine kinetics in this process. Methods. Male Lewis rats were used. IPC was administered with a IO-minute i schemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia. Changes in the adenosine concentrations in liver tissue were evaluated, and the effects of adenosine A(1) or A(2) receptor agonists or antagonists were, examined either in place of or against IPC. Results. The 7-day animal survival was significantly better in the IPC grou p than in the control group (87% vs 53%; n = 15, P < .05). The release of l iver-related enzymes during reperfusion was suppressed better in the IPC gr oup (P < .01). Recovery of adenosine triphosphate levels was faster in the LPC group (P < .01). After IPC, adenosine concentrations in liver tissue im mediately increased to 1555 +/- 299 pmol/g wet tissue and were maintained a t that level during a subsequent 45-minute ischemia. The ischemic tolerance generated by IPC was mimicked by the administration of adenosine A(2) rece ptor agonist and opposed by adenosine A(2) receptor antagonist. Conclusions. The ischemic tolerance of the liver immediately after IPC can be supplanted by selective pharmacologic stimulation of adenosine A(2) rece ptors.