Myocardial Protective Effect of Phentolamine in Hypertrophied Hearts During Global Ischemia
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Increased alpha adrenergic sensitivity has been demonstrated to be associated with myocardial ischemia and reperfusion. The present study was designed to assess if a protective effect is exerted by phentolamine, an imidazoline alpha adrenergic blocking agent, on hypertrophied hearts subjected to global ischemia and reperfusion. Spontaneously hypertensive male rats weighing 300-400 grams were studied on an isolated working heart preparation, maintaining constant preload (15 mm Hg) and afterload (80 mm Hg). Hearts were perfused with oxygenated Krebs-Heinsleit buffer. Every heart received 12 ml aortic root injections at a constant pressure of 80 mm Hg at the initiation of ischemia and immediately prior to reperfusion. Normothermic (38°C) and hypothermic (25°C) hearts were given one of three injection regimens. Control hearts (n=ll) received two injections of 0.9N saline. Experimental hearts (n=20) received phentolamine (25 mcg/ml) followed by saline or saline followed by phentolamine. Optimum drug concentration was determined by dose response curve analysis. Aortic output (A.O.), aortic pressure, heart rate and coronary flow were recorded during the working mode before and after ischemia. Normothermic hearts were made ischemic for 30 minutes and hypothermic hearts for 90 minutes. Eighteen of 20 hearts treated with phentolamine survived ischemia whereas one of 11 control hearts recovered. Recovery of function at 38°C was significantly improved by phentolamine given at initiation (p < 0.001) or at the conclusion (p< 0.001) of ischemia. This difference persisted at 25°C comparing controls to phentolamine/saline (p< 0.0001) or saline/phentolamine (p< 0.06) hearts. This data indicates that treatment of the ischemic hypertrophied heart with an alpha adrenergic blocker prior to the onset of ischemia or before reperfusion provides significant myocardial protection.