DIFFERENTIAL-EFFECTS OF ADENOSINE PRECONDITIONING ON THE POSTISCHEMICRAT MYOCARDIUM

Ischemic preconditioning describes the phenomenon of endogenous myocar dial protection against sustained ischemia-reperfusion injury (I/R). A lthough the complex stimulus of transient ischemia induces global myoc ardial protection against acidosis, infarction, and stunning, it is un known 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 mu M coronary con centration) or vehicle 10 min prior (preconditioning) to global myocar dial I/R (20 min/40 min; 37 degrees C). To determine whether adenosine affects stunning, continuous functional data (rate pressure product a nd coronary flow) were obtained. To determine whether adenosine affect s necrosis, creatine kinase (CK) loss into the coronary effluent was d etermined during postischemic reflow. To determine whether adenosine a ffects pH, continuous pH measurements were made using NMR. Results ind icate that adenosine protects against stunning but provides only minim al protection against acidosis. Adenosine's protection of function occ urs despite severe acidosis. Adenosine does not limit CK loss. We conc lude that (1) adenosine preconditioning, a component of ischemic preco nditioning, protects myocardial function following I/R, but does not p rovide global myocardial protection against I/R in the rat; (2) protec tion of function can occur despite severe ischemic acidosis; and (3) p rotection of function occurs despite equivalent postischemic CK loss. These results suggest that pharmacologic preconditioning may require m ultiple agents in order to provide global myocardial protection. (C) 1 996 Academic Press, Inc.