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Reversibility of acute alcohol cardiac depression: 31P NMR in hamsters
W Auffermann1, S Wu, W W Parmley
1Cardiovascular Research Institute, University of California, San Francisco 94143.
Insights
Acute alcohol exposure reversibly depresses heart function, increasing intracellular calcium. Verapamil pretreatment protected hamster hearts from this cardiac depression without impacting energy reserves.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Biochemistry
Background:
- Acute alcohol exposure can lead to cardiac dysfunction.
- Calcium homeostasis plays a critical role in cardiac contractility.
- The effects of specific calcium channel blockers on alcohol-induced cardiac depression are not fully understood.
Purpose of the Study:
- To investigate the effects of acute alcohol exposure on isolated hamster heart function and energy metabolism.
- To evaluate the protective potential of verapamil and diltiazem against alcohol-induced cardiac depression.
- To assess the impact of alcohol and drug pretreatment on intracellular calcium levels and high-energy phosphates.
Main Methods:
- Isolated hamster hearts were perfused with ethanol and subsequently with control medium.
- Groups were pretreated with verapamil or diltiazem.
- Cardiac function (developed pressure, end-diastolic pressure) was measured.
- Energy metabolites (ATP, Pi, PCr) were analyzed using 31P NMR.
- Intracellular calcium was quantified using atomic absorption spectrophotometry.
Main Results:
- Ethanol perfusion significantly reduced developed pressure and increased end-diastolic pressure, with decreased ATP and increased Pi.
- Verapamil pretreatment partially attenuated cardiac depression during ethanol exposure.
- Diltiazem showed no protective effect.
- Cardiac function recovered after ethanol removal, with verapamil-pretreated hearts showing better performance.
- Intracellular calcium normalized post-ethanol, and high-energy phosphates remained largely unchanged during and after alcohol exposure.
Conclusions:
- Functional cardiac depression from acute alcohol exposure is reversible.
- Verapamil offers cardioprotection against alcohol-induced depression by potentially modulating intracellular calcium.
- Energy metabolism is not significantly altered by acute alcohol exposure or verapamil treatment in this model.
Abstract:
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.