Regional Blood Flow and Cerebral Metabolic Changes during Alcohol Withdrawal and Following Midazolam Therapy

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Abstract
Regional blood flows and cerebral oxygen consumption (CMRO2) were measured following alcohol withdrawal in alcohol-dependent rats. In addition, the authors tested the ability of midazolam (0.057, 0.575, or 5.75 mg .cntdot. kg-1) to modify alcohol-induced changes. Rats received a 3-week treatment of daily ad libitum access to a liquid diet containing 6.54% ethanol or a sham treatment with the same caloric intake but with white dextrin substituted for alcohol. Regional blood flow was measured 12 h after alcohol withdrawal with radioactive microspheres. Nitrous oxide (70% in oxygen) was used as the control anesthetic. Rats withdrawn from alcohol treatment had significantly increased heart rate, cortical cerebral blood flow (CBF) (39 .+-. 8%, mean .+-. SE), and CMRO2 (41 .+-. 9%) compared with sham-treated rats (P < 0.05). Subcortical CBF (49 .+-. 8%), myocardial (52 .+-. 18%), and hepatic arterial blood flow (298 .+-. 47%) also were increased in alcohol-withdrawn rats. Renal blood flow decreased 47 .+-. 5%, while skeletal muscle and small intestinal blood flow were not significantly different between the two groups. Midazolam infusion decreased CBF, CMRO2, and hepatic arterial blood flow in alcohol-withdrawn rats to similar levels as sham-treated rats and increased renal blood flow in both groups. Skeletal muscle and intestinal tissues showed no change in blood flow in response to midazolam. The authors conclude that midazolam may be effective in lowering blood pressure and brain metabolism and reversing regional blood flow changes produced by alcohol withdrawal in the rat.