Cardiac preconditioning protects against irreversible injury rather than attenuating stunning.

Abstract 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 α 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°C) and reperfusion (40 min). The PC group received an α 1 -adrenergic stimulus (norepinephrine, 0.5-1.0 μ M , 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 β-adrenergic pathway stimulus (forskolin (FSK), 100 μ M 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 1 -adrenergic PC improves postischemic cardiac function by preventing irreversible injury. Furthermore, α 1 -adrenergic PC improves the postischemic response to inotropic stimulation by 36.7%.