Differential effects of adenosine preconditioning on the postischemic rat myocardium

Ischemic preconditioning describes the phenomenon of endogenous myocardial protection against sustained ischemia-reperfusion injury (I/R). Although the complex stimulus of transient ischemia induces global myocardial protection against acidosis, infarction, and stunning, it is unknown whether select components of transient ischemia (e.g., adenosine) are responsible for different aspects of protection. To study this, isolated rat hearts were treated with adenosine (125 microM coronary concentration) or vehicle 10 min prior (preconditioning) to global myocardial I/R (20 min/40 min; 37 degrees C). To determine whether adenosine affects stunning, continuous functional data (rate pressure product and coronary flow) were obtained. To determine whether adenosine affects necrosis, creatine kinase (CK) loss into the coronary effluent was determined during postischemic reflow. To determine whether adenosine affects pH, continuous pH measurements were made using NMR. Results indicate that adenosine protects against stunning but provides only minimal protection against acidosis. Adenosine's protection of function occurs despite severe acidosis. Adenosine does not limit CK loss. We conclude that (1) adenosine preconditioning, a component of ischemic preconditioning, protects myocardial function following I/R, but does not provide global myocardial protection against I/R in the rat; (2) protection of function can occur despite severe ischemic acidosis; and (3) protection of function occurs despite equivalent postischemic CK loss. These results suggest that pharmacologic preconditioning may require multiple agents in order to provide global myocardial protection.