The long-term objective of this proposal is to determine the relationship between chronic alcoholism and infection-induced depression of cardiac function. Since chronic alcoholism itself has been shown to induce a cardiomyopathy, we hypothesize that chronic alcoholism will enhance the sensitivity of the myocardium to infection-induced dysfunction. This enhanced sensitivity of the myocardium of the alcoholic may contribute to a greater severity of sepsis and a recovery that is plagued with more compilications.
The specific aims of this study are to compare myocardial performance in septic, chronically alcoholic and septic, nonalcoholic rats and to elucidate the control mechanisms that play a role in the development of the dysfunctions and in the potentiation of the two insults. These studies will use the isolated perfused working heart preparation to assess ventricular performance- both volume pumped (cardiac output) and pressure generated. Cardiac performance, in the preparation, is independent of neurohumoral agents which can affect contractile performance under in vivo conditions. Such agents as catecholamines and infection-induced mediator release will not be present and thee- fore intrinsic contractile performance can be asssessed. In addition, intrinsic compliance and myocardial substrate utilization will be studied in alcoholic and non-alcoholic rats with and without bacterial infection. The ability of cardiac tissue to respond to catecholamine stimulation will be assessed in alcoholic rats with and without sepsis and in appropriate control animals. These studies will evaluate chrono-tropic and inotropic functional responses to B-adrenergic stimulation in isolated atria and isovolumically contracting hearts. In addition, biochemical characterization of isolated myocytes from alcoholic and nonalcoholic rats with and without sepsis will be determined by measuring cAMP accumulation in response of catecholamine stimulation and B-receptor binding parameters with radioligands. These studies will dissociate alcohol and infection changes by alcoholism. Finally, the reversal of the alcohol-induced dysfunction and the alcohol potentiation of infection-induced dysfunction will be assessed by gradually withdrawing alcohol from the animals diet and assessing cardiac pump function, substrate utilization and catecholamine responsiveness.
