Anti-Stunning and Anti-Infarct Effects of Adenosine-Enhanced Ischemic Preconditioning

Abstract

Background —Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing post-ischemic functional recovery. In this study, the anti-infarct effects and the anti-stunning effects of APC in contributing to enhanced post-ischemic functional recovery were determined and compared with IPC. Methods and Results —Sheep (n=96) were subjected to 15, 30, 45, or 60 minutes 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 before ischemia/reperfusion. Regional ischemia (RI) hearts received no pretreatment. Infarct size/area at risk was determined by tetrazolium staining. Regional myocardial function was determined by sonomicrometry. Segment shortening 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. Segment 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/area 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% and 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 IPC exhibit anti-infarct and anti-stunning effects in the ovine heart, but these effects are rapidly diminished with IPC. APC significantly extends these effects, providing for significantly enhanced infarct size reduction and post-ischemic functional recovery ( P <0.05 versus IPC).