Tolerance to ethanol and cross-tolerance to pentobarbital by isolated hearts from chronic alcoholic rats.
The effects of ethanol and pentobarbital on the function of isolated working hearts from control and ethanol-fed male Long-Evans rats were studied. Hearts from ethanol-fed animals (38% of calories; 10-12 months) exhibited functional tolerance to the cardiodepressive effects of 18-71 mM ethanol in the perfusing medium. Left ventricular systolic pressure, peak relaxation rate, isovolumic pressure indexes, peak aortic flow rate, cardiac output, and stroke work of the control hearts were depressed to a greater extent than were those indexes of the alcoholic rat hearts during exposure to ethanol in vitro. Differences in the functional responses of controls and alcoholics were not the result of differences in energetics; myocardial O2 consumption, O2 supply-to-utilization ratio, and external work efficiency changed similarly in both groups of hearts during perfusion with ethanol. Cross-tolerance of the alcoholic rat hearts to the in vitro cardiodepressive effects of pentobarbital was also apparent. Peak rate of left ventricular pressure development, peak aortic flow rate, isovolumic pressure indexes, and cardiac output of the control rat hearts were significantly lower than those indexes of the alcoholic rat hearts during perfusion with 0.5 mM pentobarbital. In addition, four of the seven control hearts could not be paced during pentobarbital perfusion using 3V electrical pulses; the pacing voltage had to be raised and right ventricular pacing used to maintain stable function of those hearts at a 321 beats/min pacing rate. Myocardial O2 consumption and O2 supply-to-utilization ratios of control and alcoholic rat hearts were similar, but external work efficiency was slightly higher in the alcoholics than in controls during pentobarbital perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Segel
L D
LD
Department of Internal Medicine, University of California School of Medicine, Davis 95616.
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010424:Pentobarbital / Q000008:administration & dosage / Q000633:toxicity*; D010477:Perfusion; D051381:Rats
D000431:Ethanol; D010424:Pentobarbital