Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotect ion of ischemic preconditioning (IPC) by both significantly decreasing myoc ardial infarct size and significantly enhancing postischemic functional rec overy. In this study, the role of adenosine receptors during ischemia-reper fusion was determined. Rabbit hearts (n = 92) were used for Langendorff per fusion. Control hearts were perfused for 180 min, global ischemia hearts re ceived 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-m in ischemia and 5-min reperfusion before ischemia. APC hearts received a bo lus injection of adenosine coincident with IPC. Adenosine receptor (A(1),A( 2), and A(3)) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A(1)/ A(3)) and MRS-1191/MRS-1220 (A(3)) significan tly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during bo th ischemia and reperfusion (P< 0.05 vs. APC). DPCPX (A(1)) administered ei ther before ischemia and/or during reperfusion had no effect on APC cardiop rotection. APC-enhanced infarct size reduction is modulated by adenosine re ceptors primarily during ischemia, whereas APC-enhanced postischemic functi onal recovery is modulated by adenosine receptors during both ischemia and reperfusion.