Adenosine-enhanced ischemic preconditioning decreases infarct in the regional ischemic sheep heart

Background. Recently we have reported a myoprotective protocol, adenosine-enhanced ischemic preconditioning, that extends the protection afforded by ischemic preconditioning in the isolated crystalloid-perfused heart. In this report the efficacy of adenosine-enhanced ischemic preconditioning in the in situ blood-perfused heart was investigated. Methods. Sheep were subjected to 60 minutes of regional ischemia and 120 minutes of reperfusion. Ischemic preconditioned hearts received 5 minutes of zero flow regional ischemia and 5 minutes of reperfusion before regional ischemia. Adenosine-enhanced ischemic preconditioned hearts received a bolus injection of 10 mmol adenosine at the immediate start of ischemic preconditioning. Adenosine-treated hearts received an adenosine bolus, 10 minutes before regional ischemia. The ratio of infarct size to area at risk and mechanical function were determined. Results. The infarct size to area at risk ratio in regional ischemia was 55.4% ± 2.1%. This ratio was significantly decreased with ischemic preconditioning and adenosine (22.2% ± 2.2% and 19.3% ± 1.4%, respectively; p < 0.001 versus regional ischemia) and adenosine-enhanced ischemic preconditioning (8.0% ± 2.0%, p < 0.001 versus regional ischemia and ischemic preconditioning, and p < 0.01 versus adenosine). Conclusions. Adenosine-enhanced ischemic preconditioning significantly decreases infarct size in the in situ blood-perfused heart and provides superior protection compared with ischemic preconditioning.