John S. Vasko

The effects of morphine on the resistance and capacitance vessels of the peripheral circulation

Abstract The effects of morphine on total peripheral vascular resistance and the capacity of the peripheral vascular compartment were determined in normal dogs. In 13 animals, in which systemic flow was maintained constant, morphine (1 mg. per kilogram) caused immediate decreases in resistance averaging 46 ± 20 per cent of the control values. The decrease in resistance was transient, and normal or increased resistance was noted 30 minutes after the drug was administered. This effect of morphine on resistance vessels was indirect, however, since no immediate change in pressure occurred when morphine was injected into an isolated perfused vascular bed. In 13 dogs, studied during cardiopulmonary bypass, the capacity of the total peripheral vascular compartment increased after the administration of morphine. Blood volume rose an average of 11 ± 6 ml. per kilogram, and systemic venous return, measured with a flowmeter, rapidly decreased after the injection. Venous tone, determined by major-vessel occlusion in 8 dogs, decreased from 6.8 ± 1.3 to 3.5 ± 1.1 cm. H 2 O after morphine (0.5 mg. per kilogram) was given. The measured changes in both capacitance and venous tone occurred promptly and persisted throughout a 30-minute period of observation. The experiments indicate that increased capacitance and venous pooling are important effects of morphine on the circulation which have not been well recognized.

Mechanisms of action of morphine in the treatment of experimental pulmonary edema

Abstract The hemodynamic effects of morphine were correlated with the course of acute pulmonary edema in 18 dogs. Pulmonary edema was produced by various technics designed to simulate the clinical cardiovascular disorders in which pulmonary edema most commonly occurs. Morphine (0.5 mg./kg.) resulted in subsidence of pulmonary edema in all animals, and improvement was concomitant with striking and parallel decreases in pulmonary arterial flow and pressure and in left atrial and left ventricular enddiastolic pressures. Total pulmonary vascular resistance was measured before and after morphine administration in 12 normal dogs. A preparation was utilized in which left atrial pressure and pulmonary and systemic arterial flows were maintained constant. A slight to moderate decrease in resistance usually occurred, but the changes were variable and not of significance. The experiments indicate that the beneficial effects of morphine in pulmonary edema may be principally attributed to the effects of the drug on the capacitance vessels of the peripheral circulation. Capacity of the peripheral vascular bed is increased, systemic venous return is reduced, and improvement results from a “pharmacologic phlebotomy.”

The Effects of Mitral Regurgitation on the Pattern of Instantaneous Aortic Blood Flow Clinical and Experimental Observations

Instantaneous ascending aortic blood flow was recorded at operation in five patients with severe, pure mitral regurgitation, and in nine dogs in which mitral regurgitation was produced experimentally under controlled conditions. In both the patients and the experimental animals, the pattern of aortic flow was abnormal during mitral regurgitation: peak flow occurred early, the percentage of total forward flow was abnormally high during the first half of the ejection period and abnormally low during the last quarter. When stroke volume, heart rate, and aortic pressure were maintained constant, mitral regurgitation also resulted in increases in peak flow, mean ejection rate, and maximum acceleration of flow. These abnormalities of the aortic flow patterns are attributable to inability of the ventricle to sustain forward ejection during late systole in the presence of severe regurgitant flow through the mitral valve.

Can outflow obstruction be induced within the normal left ventricle

Abstract Previously reported experimental studies have indicated that outflow obstruction can be produced within the normal left ventricle of the dog under conditions of reduced cardiac output or augmented myocardial contractile force, or both. This hypothesis was re-examined in the experiments described. In 36 normal dogs, isoproterenol and other inotropic drugs were administered before and during hemorrhagic shock or a period of controlled decreased venous return. In 21 dogs, systolic pressure gradients between the left ventricle and central aorta were recorded when left ventricular pressure was measured from a catheter introduced from the aorta or left atrium. The elevated left ventricular pressures responsible for the gradients were shown to be artifacts, however, when the pressure was simultaneously measured from a catheter in the apex of the ventricle. It is concluded that there is presently no valid hemodynamic evidence that outflow obstruction can be induced within the normal ventricle of the dog, and consideration is given to possible mechanisms responsible for the factitious pressure pulses recorded in these and other investigations.