Alcohol intoxication results in rapid loss in free magnesium in brain and disturbances in brain bioenergetics: relation to cerebrovasospasm, alcohol-induced strokes, and barbiturate anesthesia-induced deaths.
In vivo 31P-nuclear magnetic resonance (31P-NMR) spectroscopy and ion-selective electrode measurements were undertaken to determine if administration of acute doses of alcohol (ALC, 0.2-6.6 g/kg), and lethal doses of barbiturate anesthesia, exert any influence on: (1) brain cellular bioenergetics, intracellular free Mg ([Mg2+]i) and intracellular pH (pHi), and (2) serum levels of ionized Mg (IMg2+), ionized calcium (ICa2+) and K+. Approximately 20-30 min after intraperitoneal administration of ALC to anesthetized rats, brain phosphocreatine (PCr)/ATP and PCr/inorganic phosphate (P(i)) ratios dropped from 2.5 to 1.7 and from 6.6 to 2.2, respectively, P(i) rose 20-200% (depending upon ALC dose), and free ADP and creatine rose significantly. ALC induced rapid decreases in the cytosolic phosphorylation potential (CPP) and free energy of ATP hydrolysis (-delta G/delta E). Following ALC administration, brain [Mg2+]i dropped rapidly (within 4-30 min) and significantly; the greater the dose of ALC, the greater the loss in brain [Mg2+]. Correlations were found between [Mg2+]i, PCr/ATP, CPP and delta G/delta E after ALC but not in control brains. Rats that exhibited ALC-induced strokes and death (unlike barbiturate death) exhibited huge elevations in [Mg2+]i. Although ALC administration does not alter brain pHi at least (up to 70 min), ALC- and barbiturate-induced death produces rapid brain intracellular acidosis. Concomitant with ALC-induced alterations in [Mg2+]i and brain cellular bioenergetics, we noted that ALC administration results in rapid elevations in serum IMg2+ and K+ but not ICa2+. These results suggest that ALC administration and heavy or binge-drinking of ALC (1) can result in rapid alterations in brain bioenergetics, [Mg2+]i and pHi, and (2) result in rapid elevations in serum IMg2+ and K+ in rats. In addition, ALC- and barbiturate-induced deaths do not appear to produce identical alterations in brain bioenergetics and [Mg2+]i, and lastly binge or heavy drinking of ALC may result in stroke-like events and sudden death via rapid alterations in brain cellular bioenergetics.
Altura
B M
BM
Department of Physiology, SUNY Health Science Center, Brooklyn.
Altura
B T
BT
Gupta
R K
RK
D000435:Alcoholic Intoxication / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001463:Barbiturates / Q000633:toxicity; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology; D008274:Magnesium / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D001463:Barbiturates; D000431:Ethanol; D008274:Magnesium; D011188:Potassium; D002118:Calcium