PROTECTION OF MYOCARDIUM BY TRANSIENT, PREISCHEMIC ADMINISTRATION OF PHENYLEPHRINE IN THE RABBIT

Background: Transient ischemia protects the myocardium from subsequent, more prolonged ischemic episodes; however, other forms of stress before ischemia might also provide a preconditioning effect. Our objective was to test the hypothesis that phenylephrine, an alpha-adrenergic agonist, given before ischemia can act as a pharmacologic preconditioning agent and protect the myocardium. Methods: Phenylephrine, 50 mu g/kg, was given as a bolus 15 min before coronary artery occlusion in 11 anesthetized open-chest rabbits; 12 control rabbits received saline. All rabbits underwent 30 min coronary artery occlusion and 4 h reperfusion. Regional myocardial blood flow was quantified using radioactive microspheres, infarct size by tetrazolium staining, and risk zone by blue dye. Results: Pretreatment with phenylephrine significantly reduced necrosis. Infarcted myocardium comprised 23+/-4% of the region at risk in treated rabbits compared with 39+/-4% in control animals (P<0.01). Mean systolic arterial pressure increased briefly after administration of phenylephrine (98+/-5 to 141+/-7 mmHg) but returned to baseline before occlusion. Heart rate was similar in both groups at baseline but decreased slightly with phenylephrine treatment. Regional myocardial blood flow increased after injection of the phenylephrine bolus to 2.86+/-0.22 compared with 2.25+/-0.08 ml/min/g in control animals (P=0.02), but both groups were equally ischemic during occlusion. Conclusion: Transient, preischemic treatment with phenylephrine makes the myocardium more resistant to necrosis during ensuing ischemia and reperfusion.