CARDIAC PRECONDITIONING PROTECTS AGAINST IRREVERSIBLE INJURY RATHER THAN ATTENUATING STUNNING

The purpose of this experiment was to determine if cardiac preconditio ning (PC) mediates protection by attenuating stunning or preventing ir reversible injury. Inherent in the definition of myocardial stunning i s the ability to respond to catechol stimulation after ischemia/reperf usion (I/R). Irreversibly injured myocardium cannot respond to catecho ls. We hypothesized that alpha(1)-adrenergic-stimulated PC is mediated through a functional protection against reversible injury. We investi gated this hypothesis in the isolated, buffer-perfused rat heart subje cted to global ischemia (20 min, 37.5 degrees C) and reperfusion (40 m in). The PC group received an alpha(1)-adrenergic stimulus (norepineph rine, 0.5-1.0 mu M, 2 min) 10 min prior to ischemia. Control hearts we re perfused normoxically for 80 min. Developed pressure (DP) and heart rate were recorded continuously, To determine maximal myocellular fun ction, all hearts received a beta-adrenergic pathway stimulus (forskol in (FSK), 100 mu M bolus) at end reperfusion. The ability to improve D P in response to FSK was indicative of reversible dysfunction (stunnin g). Failure to attain the maximal DP established in normoxic controls was utilized as a measure of irreversible dysfunction, Recovery was as sessed as a percentage of initial DP. The results suggest that (1) PC protects against an I/R injury (recovery: I/R, 50.1%; PC + I/R, 76.0%; P < 0.05); (2) all groups exhibit reversible dysfunction (all increas ed DP in response to FSK); (3) when maximally stimulated, I/R hearts a re unable to develop pressures similar to those of normoxic controls, suggesting irreversible injury; and (4) PC hearts, however, attained s imilar maximal pressures compared to controls. We conclude that alpha( 1)-adrenergic PC improves postischemic cardiac function by preventing irreversible injury. Furthermore, alpha(1)-adrenergic PC improves the postischemic response to inotropic stimulation by 36.7%. (C) 1995 Acad emic Press, Inc.