Alteration of carbon monoxide and hypoxic hypoxia-induced lethality following phenobarbital, chlorpromazine, or alcohol pretreatment

Abstract

Mice were pretreated with phenobarbital, chlorpromazine, or alcohol prior to exposure to 1900 ppm carbon monoxide (CO) or 7.5% oxygen (O 2) environments. Pretreatment for 1 hr with chlorpromazine or ethanol increased the lethality of mice exposed to both CO and 7.5% O 2, while 1-hr phenobarbital pretreatment had no effect on CO lethality but increased 7.5% O 2 lethality. Changes in carboxyhemoglobin concentrations that were observed were inconsistent with the alteration in CO lethality. Studies of red blood cell 2,3-diphosphoglycerate concentrations and rate of carboxyhemoglobin formation in vitro showed that the apparent affinity of hemoglobin for oxygen and CO remained unchanged following drug or alcohol pretreatments. The different effects of the pretreatments on CO and 7.5% O 2 lethality and the lack of correlation of CO lethality with carboxyhemoglobin concentrations suggests that there are other factors besides extracellular events directly associated with oxygenation of tissues which are critical determinants of the lethal potential of CO or 7.5% O 2.