Decreased beating rate variability of spontaneously contracting cardiomyocytes after co-incubation with endotoxin

Abstract

Decreased heart rate variability (HRV) in critically ill patients indicates a poor prognosis. In heart failure patients, there is an elevated sympathetic tone, reflected by a dominance of sympathetic parameters in HRV, whereas in critically ill patients sympathetic and parasympathetic modulation of heart rate is attenuated despite increased catecholamine blood levels. Thus, autonomic dysfunction in the critically ill cannot be causally related to an impairment at the level of neural transmission, but may be due to a derangement of signal transduction at the effector cell level. On the basis of our working hypothesis that endotoxin may be involved in this blunting of effector cell response to nerval input, we studied the spontaneous beating of cardiomyocytes under the influence of endotoxin. Applying the clinically established indices of HRV to the analysis of beating rate variability (BRV) of neonatal rat cardiomyocytes in serum-free medium, a narrowing of their BRV by endotoxin is demonstrated. We propose that the narrowing of HRV in critically ill patients does not only reflect the altered input from the central or peripheral neurons, but rather a remodeling of the cardiac pacemaker cells by endotoxin and inflammatory mediators.