Anti-stunning and anti-infarct effects of adenosine-enhanced ischemic preconditioning

Background-Adenosine-enhanced ischemic preconditioning (APC) extends the pr otection afforded by ischemic preconditioning (IPC) by both significantly d ecreasing infarct size and significantly enhancing post-ischemic functional recovery. In this study, the anti-infarct effects and the anti-stunning ef fects of APC in contributing to enhanced post-ischemic functional recovery were determined and compared with IPC. Methods and Resnlts-Sheep (n=96) were subjected to 15, 30, 45, or 60 minute s of regional ischemia and 120 minutes of reperfusion. IPC hearts received 5 minutes of regional ischemia and 5 minutes of reperfusion before ischemia /reperfusion. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine hearts (ADO) received a bolus injection of adenosine b efore ischemia/reperfusion. Regional ischemia (RI) hearts received no pretr eatment. Infarct size/area at risk was determined by tetrazolium staining. Regional myocardial function was determined by sonomicrometry. Segment shor tening after 15 minutes of ischemia in which no infarct was incurred was 32 .1+/-10.6% in RI, 70.6+/-8.5% in IPC, and 77.4+/-6.0% in APC hearts. Segmen t shortening after 30 minutes of ischemia was 60.7+/-6.3% in APC hearts (P< 0.05 versus RI, ADO, IPC) but was <37% in all other groups. Infarct size/ar ea at risk after 30 and 60 minutes of ischemia was, respectively, 25.8+/-5. 7% and 49.8+/-6.0% in RI, 12.9+/-3.0% and 29.2+/-5.0% in ADO, 11.6+/-2.4% a nd 24.6+/-2.7% in IPC, and 5.1+/-1.6% and 12.4+/-2.0% in APC hearts (P<0.05 versus RI, ADO, IPC). Conclusions-APC and TPC exhibit anti-infarct and anti-stunning effects in t he ovine heart, but these effects are rapidly diminished with IPC. APC sign ificantly extends these effects, providing for significantly enhanced infar ct size reduction and post-ischemic functional recovery (P<0.05 versus IPC) .