The purpose of this experiment was to determine if cardiac preconditioning (PC) mediates protection by attenuating stunning or preventing irreversible injury. Inherent in the definition of myocardial stunning is the ability to respond to catechol stimulation after ischemia/reperfusion (I/R). Irreversibly injured myocardium cannot respond to catechols. We hypothesized that alpha 1-adrenergic-stimulated PC is mediated through a functional protection against reversible injury. We investigated this hypothesis in the isolated, buffer-perfused rat heart subjected to global ischemia (20 min, 37.5 degrees C) and reperfusion (40 min). The PC group received an alpha 1-adrenergic stimulus (norepinephrine, 0.5-1.0 microM, 2 min) 10 min prior to ischemia. Control hearts were perfused normoxically for 80 min. Developed pressure (DP) and heart rate were recorded continuously. To determine maximal myocellular function, all hearts received a beta-adrenergic pathway stimulus (forskolin (FSK), 100 microM bolus) at end reperfusion. The ability to improve DP in response to FSK was indicative of reversible dysfunction (stunning). Failure to attain the maximal DP established in normoxic controls was utilized as a measure of irreversible dysfunction. Recovery was assessed 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 increased DP in response to FSK); (3) when maximally stimulated, I/R hearts are unable to develop pressures similar to those of normoxic controls, suggesting irreversible injury; and (4) PC hearts, however, attained similar maximal pressures compared to controls. We conclude that alpha 1-adrenergic PC improves postischemic cardiac function by preventing irreversible injury.(ABSTRACT TRUNCATED AT 250 WORDS)