Effects of nitroglycerin on transmural energy metabolism in the underperfused canine heart

Abstract

Effects of nitroglycerin on hemodynamics and transmural distribution of myocardial metabolites were studied at 40% of control coronary perfusion pressure induced by acute coronary stenosis in the canine heart. At 40% of coronary perfusion pressure, high energy phosphate (ATP, creatine phosphate) contents significantly diminished in all layers, especially in the inner layer. A 0.3 micrograms/kg/min intracoronary infusion of nitroglycerin showed no direct effects on energy metabolism in the underperfused myocardium. A 3 micrograms/kg/min i.v. administration of the drug under fixed coronary constriction resulted in decrease in left ventricular peak systolic pressure and systemic blood pressure, and further decrease in coronary perfusion pressure and coronary blood flow. Left ventricular end diastolic pressure and ST-segment of the epicardial ECG were elevated. High-energy phosphate contents further decreased while inorganic phosphate and lactate showed an increase. Under these conditions, release of the constriction sufficient for retention of the coronary perfusion pressure at about 40 mm Hg resulted in significant improvement of the myocardial energy metabolism without a further increase in coronary blood flow. The results suggest that when the myocardium is underperfused due to undilatable stenotic vessels with maximum autoregulation of the regional flow, it may be dangerous to administer nitroglycerin in a dose sufficient to produce a large decrease in coronary perfusion pressure.