Anesthetic Depression of Myocardial Contractility

Abstract

The bulk of experimental evidence indicates that anesthetics do not produce their negative inotropic effect via an inhibitory action on mitochondrial electron transport. Anesthetics decrease energy need, rather than energy production. Anesthetics also decrease the rate of sequestration of Ca2+ by mitochondria, but, again, this appears not to be an important cause of reduced myocardial contractility. The role played by direct anesthetic depression of the myofibrils in reducing contractility is uncertain. Most experimental evidence now available suggests that significant myofibrillar depression, measured in terms of inhibition of actomyosin ATPase activity or inhibition of force production, occurs only at anesthetic concentrations which are high compared to concentrations employed clinically. This would seem to indicate that the myofibrils are not an important target for anesthetics in regard to the production of depressed myocardial contractility. However, the experimental act of removing myofibrils from their intracellular environment, or of removing the sarcolemma or making it hyperpermeable, appears to prevent some regulatory myofibrillar phosphorylation reactions from taking place. As stated by Winegrad, "certain forms of regulation of the cardiac myofibril are fragile and can be seen only when cellular constituents and structure are maintained." It is possible that this type of regulation is susceptible to inhibition by anesthetics. Methods for preserving this regulation are available, and will need to be employed before a depressant action of anesthetics on the myofibril can be definitely dismissed as a significant cause of the inhibition of cardiac contractility. A single study, of intracellular Ca2+ levels in the intact cell (where myofibrillar regulation was presumably preserved), has indicated that halothane may decrease myofilament Ca2+ sensitivity. However, for reasons stated above, this study cannot be taken as unequivocal proof of such an action. Despite the fact that the normal action potential is little affected by anesthetics, the sarcolemma appears to play a pivotal role in the production of anesthetic-induced contractile depression. Significant depression of the rate of upstroke of the slow (Ca2+-mediated) action potential by clinical concentrations of both inhalation and intravenous anesthetics has been demonstrated by several workers. This has been interpreted to mean that anesthetics inhibit the influx of Ca2+ through the slow channel, and such has been confirmed (to date, for halothane and thiamylal) by direct measurement of the slow inward Ca2+ current using a voltage clamp technique.(ABSTRACT TRUNCATED AT 400 WORDS)