Effect of drugs on myocardial contractility in the intact dog and in experimental myocardial infarction: Basis for their use in cardiogenic shock

Abstract

Drugs used in cardiogenic shock, namely, norepinephrine, norepinephrine plus phentolamine, metaraminol, isoproterenol and methoxainine, were experimentally evaluated by investigating their effects on myocardial forcevelocity relation in normal closed chest dogs. Further, the differential effects of these drugs on ischemic and nonischemic portions of the myocardium were appraised in open chest experiments in which acute myocardial infarction had been induced. The velocity of shortening of fibers was measured with the newly devised strain-gauge catheter assembly. These studies have shown that the desired increase in myocardial contractility and aortic pressure may best be accomplished by a combination of norepinephrine and phentolamine; the latter, in appropriate amounts, counteracts the excessive increase in peripheral resistance induced by norepinephrine. Isoproterenol, which augments contractility, may prove effective when peripheral resistance is adequate. Methoxamine, on the other hand, is least suited, since it has no effect on the myocardial contractile state and the increase in pressure load leads to a reciprocal decline in velocity of contraction and an increase in left ventricular end-diastolic pressure. Since most of these drugs act by increasing the velocity of contraction or by increasing afterload, or both, the effect of these variables oil myocardial oxygen demand is highly pertinent to the clinical use of these drugs. The action of these drugs in augmenting the magnitude of paradoxic systolic stretching of the fibers of the ischemic myocardium and the resulting increase in dissipation of ventricular pressure expended in producing such distention is regarded as an important factor working against the effectiveness of drug therapy.