Myocardial protective effect of amiodarone in hypertrophied hearts during global ischemia

The effect of amiodarone on the ischemic-reperfusion injury was tested in an isolated working preparation, using hypertrophied rat heart at 37 degrees C. Constant filling and afterload pressures and similar heart rates were used. Hearts from spontaneously hypertensive rats (N = 78) had thirty minutes of ischemia. Each received a 12-ml injection, by aortic root infusion, of amiodarone in normal saline or of normal saline alone at 37 degrees C at the onset of ischemia. Heart rate, aortic output, coronary sinus output, atrial pressure, and aortic pressure were recorded before and after global ischemia under steady-state conditions. Dose-response studies were performed at concentrations of 0.01 to 1.0 mg/ml. At every dose administered, amiodarone was found to significantly ameliorate the deleterious effects of global ischemia. The maximal benefit of amiodarone (70 +/- 4.6% recovery of function [mean +/- standard error of the mean], p less than 0.01) was found to be 0.25 mg (0.021 mg/ml), or 0.11 mg/g wet heart weight. Improvement in survival (return of aortic output and heart rate following ischemia) with all doses of amiodarone was statistically significant (p less than 0.002). Decreased recovery of function following global ischemia when doses were greater than 0.25 mg may have been secondary to the known negative inotropic effects of the drug. The mechanisms for the protective effects of amiodarone may be coronary vasodilatation, antiarrhythmic stabilization, or inhibition of calcium flux at the slow channel.