Kinetic disposition of ethanol in the neonatal piglet and hemodynamic effects in the presence and absence of 4-methylpyrazole.

The hemodynamic effects of acute ethanol intoxication and the kinetic disposition of ethanol are reported for the first time in neonatal piglets under nitrous oxide anesthesia. Two hours after a single dose of ethanol (1.4 g/kg), blood pressure decreased from 76 +/- 4 to 71 +/- 4 mm Hg (p less than 0.05) and heart rate increased from 194 +/- 10 to 227 +/- 8 beats/min (p less than 0.05; means +/- SE). By 5 hr, blood pressure dropped to 67.5 +/- 4 mm Hg and heart rate increased to 239 +/- 8 beats/min. In piglets pretreated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, there was a transient increase in blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.05) immediately after the end of the ethanol infusion. However, the hemodynamic alterations observed 2 hr after ethanol treatment alone were prevented with 4-methylpyrazole. These findings indicate that ethanol metabolites play a significant role in hemodynamic alterations observed after acute ethanol intoxication. The mean ethanol metabolic rate derived from plasma data was 94 +/- 9 mg/liter/hr. This corresponded to an apparent Km of 68 +/- 3 mg/liter and a Vm of 123 +/- 11 mg/liter/hr. The Vd was 0.966 +/- 0.031 liter/kg. The metabolic rate for ethanol, derived from plasma data, correlated with in vitro alcohol dehydrogenase activity at pH 7.4 and 25 and 37 degrees C. The optimum pH for hepatic alcohol dehydrogenase activity was 9.9.