Reversibility of acute alcohol cardiac depression: 31P NMR in hamsters.
Isolated hamster hearts were perfused with 2% ethanol for 30 min and then reequilibrated with control medium. One group of hamsters was pretreated with verapamil. Another group received diltiazem. Myocardial verapamil levels were 9.5 +/- 0.7 mg/g dry wt; diltiazem levels were 22 +/- 7 mg/g dry wt. Energy metabolites were assessed by using 31P NMR standardized with high-pressure liquid chromatography of freeze-clamped tissue. Intracellular calcium was measured by atomic absorption spectrophotometry, marking the extracellular space with K(CoEDTA). After 30 min of perfusion, untreated hamster hearts showed a 74% decrease in developed pressure, a marked increase in end-diastolic pressure, a decrease of ATP from 9.8 to 8.8 mmol, and an increase of Pi from 6.7 to 9.8 mmol, but no change of phosphocreatine (PCr) or intracellular pH (pHi). Verapamil pretreatment partially prevented cardiac depression during alcohol perfusion. Whereas diltiazem had no protective effect. After reequilibration, developed pressure and oxygen consumption significantly exceeded control values. ATP decreased to 8 mmol; pHi, PCr, and Pi showed no significant change. Verapamil-pretreated hearts showed better performance than untreated hearts without change in PCr and Pi, whereas ATP dropped slightly to 8.7 mmol. Thus, functional cardiac depression resulting from acute alcohol exposure is reversible. Increased intracellular calcium levels during alcohol exposure normalized after the removal of alcohol. There was no major change in high-energy phosphates during alcohol exposure or after the removal of alcohol. Verapamil protects the heart from functional depression during alcohol exposure without affecting energy resources.
Auffermann
W
W
Cardiovascular Research Institute, University of California, San Francisco 94143.
Wu
S
S
Parmley
W W
WW
Higgins
C B
CB
Sievers
R
R
Wikman-Coffelt
J
J
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000187:drug effects; D006224:Cricetinae; D004110:Diltiazem / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008647:Mesocricetus; D010101:Oxygen Consumption / Q000187:drug effects; D010758:Phosphorus; D014700:Verapamil / Q000494:pharmacology
D000227:Adenine Nucleotides; D010758:Phosphorus; D000431:Ethanol; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium