Ethanol effects on cardiomyocyte contractility.
Little is known about the direct cardiac effects of socially common sub-intoxication levels of ethanol. Previous studies evaluating the responses of normal cardiomyocytes to short-term ethanol exposure have utilized ethanol concentrations equivalent to extreme intoxication or lethal levels in vivo. The purpose of the present study was to investigate the contractile responses of isolated rat ventricular cardiomyocytes during exposure to relatively low concentrations of ethanol in the range 0.05-0.5% (v/v) (8.6-86 mM) under physiological conditions (3 Hz stimulation; 36 degrees C; BSA vehicle). High-speed imaging techniques were used to study the kinetics of myocyte contraction, and shortening parameters were calculated for mechanistic evaluation. The concentration-response relationship was not linear and exhibited two plateau phases, suggesting at least two mechanisms of action of ethanol on cardiomyocyte contraction. At 0.05% (8.6 mM), ethanol treatment produced a 14.4% decrease in maximum myocyte shortening. The maximum rates of cell shortening and lengthening were similarly impaired, but there was no effect on contraction cycle timing at this low concentration. At 0.30% (51 mM), ethanol reduced maximum shortening by 40.2%, prolonged excitation-contraction coupling latency and abbreviated the contraction cycle time by 38%. The inotropic modulatory effect of ethanol was exaggerated in the absence of protein in the superfusion buffer. This is the first report which identifies ethanol at 0.05% (v/v) as a modulator of cardiac contractility. Kinetic analyses indicate that the mechanism of action involves disturbance of sarcoplasmic reticulum function, and this may contribute to arrhythmogenic vulnerability - especially in an in vivo context of heightened compensatory sympathetic drive.
Delbridge
L M
LM
Department of Physiology, University of Melbourne, Parkville, Victoria 3052, Australia. l.delbridge@physiology.unimelb.edu.au
Connell
P J
PJ
Harris
P J
PJ
Morgan
T O
TO
D000818:Animals; D018929:Cell Culture Techniques; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D013268:Stimulation, Chemical
D000431:Ethanol