Effects of cytokines and nitric oxide on myocardial E-C coupling.

Abstract

Compelling evidence now exists that pro-inflammatory cytokines and nitric oxide (NO) are newly identified endogenous regulators of myocardial contractility. The mechanism(s) responsible for the inotropic and chronotropic effects of these novel mediators can be explained on the basis of recently established principles of myocardial excitation contraction coupling (E-C). A novel hypothesis is proposed that cytokines and NO-mediated alterations in E-C coupling contribute to the reversible myocardial depression and beta-adrenergic desensitization observed in a diverse group of clinical conditions that activate host inflammatory responses, including congestive heart failure. The results of in vitro studies indicate that cytokines and NO have both immediate, short-term, as well as long-term effects on cardiac performance. Basic studies into these cytokine signaling pathways in cardiac myocytes have the potential to provide important new insights relevant to the design of new management strategies for the treatment of congestive heart failure patients.