Efficacy of nitroglycerin in stress-induced regional myocardial dysfunction is dependent on the chosen model: investigations in anesthetized and conscious dogs.

ABSTRACT

The antianginal efficacy of nitroglycerin (1 microgram/kg per min) was investigated in two different experimental models, one using chloralose-anesthetized open-chest dogs, the other using conscious, chronically instrumented dogs. Heart rate, arterial pressure, left ventricular dp/dtmax, and left ventricular end-diastolic pressure were registered. Left ventricular regional contractile function in the area supplied by the left circumflex coronary artery (LCX) and the left anterior descending artery (LAD) were assessed using sonomicrometry. In both models, the coronary flow reserve was limited by a hydraulic occluder around the LCX. Cardiac stimulation was achieved by a bolus injection of isoproterenol (ISO 0.5 microgram/kg) in the anesthetized animals and by graded treadmill exercise in the conscious animals. In both cases, transient contractile dysfunction occurred in the area supplied by the stenosed vessel. This contractile dysfunction was completely abolished by nitroglycerin in the conscious animals, while nitroglycerin failed to show any antianginal effect in the anesthetized dogs. Although hemodynamic differences in open and closed chest should be considered, remarkable differences in mechanisms of blood-pressure regulation according to the mode of stimulation were observed in contrast to the situation during treadmill exercise, the ISO-induced decrease in arterial blood pressure does not correspond to the clinical picture of an anginal attack. These results show that it is most important to mimic the complex pathophysiological reactions of angina pectoris in man as closely as possible in the experimental model.