Beneficial effects of high magnesium on alcohol-induced cardiac failure.
Although alcohol has long been known to induce cardiac depression and cardiomyopathy, it is not known whether drug therapy or pharmacologic manipulation can be used to prevent or reverse these toxicities. With this in mind, high levels (15 mM) of magnesium (Mg) were investigated for their potential antialcohol effects on perfused rat hearts. A high concentration of ethanol (135 mM) was used to induce rapid cardiac failure as assessed by hemodynamic and metabolic parameters. During ethanol perfusion in normal 1.2 mM [Mg2+]o physiologic salt solution, coronary flow decreased immediately, and all of the hemodynamic parameters studied (except for heart rate) were depressed significantly. After 10 min of 135 mM ethanol perfusion, only 60% of the hearts kept beating; at 15 min, only 42% of the hearts continued to beat. Myocardial metabolism under such conditions as assessed by examination of coronary effluent concentrations of lactic acid (LA), lactic acid dehydrogenase (LDH) and creatine phosphokinase (CPK) was rapidly and severely compromised. Although 15 mM MgSO4 alone did not alter coronary flow and systolic pressure under the conditions studied, it did decrease cardiac output, heart rate and total pressure developed. However, when 15 mM MgSO4 was given 10 min before ethanol, and continued during ethanol perfusion, the usual depression in all assessed cardiac hemodynamic parameters (except heart rate) caused by ethanol was not observed. During 15 min of high [Mg2+]o perfusion, coronary flow recovered from 19.1 +/- 6.8% (ethanol alone) to 68.1 +/- 9.9% of control values (p < 0.01); cardiac output recovered from 10.4 +/- 4.6% (ethanol alone) to 43.6 +/- 7.5% of control (p < 0.01); stroke volume went from 12.9 +/- 5.8% (ethanol alone) to 97.1 +/- 14.5% of control (p < 0.01); systolic pressure from 55.3 +/- 3.6% (ethanol alone) to 88.8 +/- 4.0% of control (p < 0.01), and total pressure developed from 23.9 +/- 7.8% (ethanol alone) to 35.0 +/- 4.5% of control (p < 0.05). Assessment of the metabolic biochemical parameters supported these changes in hemodynamic improvement. For example, LA, LDH and CPK all went from elevated values towards normal levels. There were similar hemodynamic and metabolic responses to high [Mg2+]o given during ethanol perfusion to that given before ethanol perfusion. The hemodynamic and metabolic beneficial effects between groups pretreated or treated with high [Mg2+]o exhibited no significant differences. These results suggest that high [Mg2+]o (15 mM) given either before or during ethanol-induced cardiotoxicity is effective in attenuating both functional and metabolic damage caused by high ethanol perfusion in the rat heart.
Zou
L Y
LY
Department of Physiology, State University of New York, Brooklyn.
Wu
F
F
Altura
B T
BT
Barbour
R L
RL
Altura
B M
BM
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D000431:Ethanol / Q000009:adverse effects*; D006323:Heart Arrest / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
D007773:Lactates; D019344:Lactic Acid; D000431:Ethanol; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D008274:Magnesium