Acute effects of ethanol on cardiac function and intracellular calcium in perfused rat heart.
OBJECTIVE
The aim was to evaluate effects of ethanol on cardiac function and intracellular Ca2+ ([Ca2+]i) in perfused rat hearts.


METHODS
A Langendorff perfused rat heart preparation was used. Changes in [Ca2+]i were evaluated by surface fluorometry in hearts loaded with Indo 1-AM.


RESULTS
Clinically relevant concentrations of ethanol (0.2 or 0.4% vol/vol) had no significant haemodynamic effects. High concentrations of ethanol (1, 2, 3, and 4% vol/vol) showed dose dependent decreases in developed pressure and the systolic peak and overall amplitude of the Indo 1 fluorescence transients (identical to [Ca2+]i), that were partially antagonised by high extracellular Ca2+ ([Ca2+]o = 4 mM). The ethanol concentrations that decreased developed pressure by 50% were 1.4 and 2.6% in the low (1.5 mM) and high [Ca2+]o, respectively. Four per cent ethanol decreased the amplitude of Indo 1 fluorescence transients to 54.5(SD 3.1) and 64.6(7.9)% of control values in the low and high [Ca2+]o, respectively. A relationship between the amplitude of Indo 1 fluorescence and developed pressure was fitted to a single sigmoid curve irrespective of [Ca2+]o. During ethanol washout, there was a dose dependent overshoot of the fluorescence ratio.


CONCLUSIONS
Only high concentrations of ethanol depressed left ventricular function in a dose dependent manner by decreasing the amplitude of [Ca2+]i transients. High [Ca2+]o partially antagonised acute alcoholic cardiac depression by increasing the amplitude of [Ca2+]i transients. [Ca2+]i is a mediator of the acute cardiac effects of ethanol in perfused intact rat hearts.
Kojima
S
S
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco 94143.
Wu
S T
ST
Wikman-Coffelt
J
J
Parmley
W W
WW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function / Q000187:drug effects
D000431:Ethanol; D002118:Calcium