In vivo toxic effects of halothane on canine cerebral metabolic pathways.
The effects of high concentrations of halothane on cerebral metabolism were examined in dogs with the aid of an extracorporeal circuit to support the systemic circulation. At blood levels exceeding those representing equilibration with 2.3% halothane, a dose-related decrease in cerebral oxygen consumption (CMR02) occurred that was unrelated to the presence or absence of an active electroencephalogram. In this circumstance, despite adequate oxygen delivery, a dose-related alteration in oxidative phosphorylation also occurred as evidenced by progressive decreases in cerebral concentrations of ATP and phosphocreatine and concomitant increases in cerebral lactate and lactate/pyruvate ratio. These effects were totally reversible, except for persistence of increased of increased CMR02, after return to low halothane concentrations. It is concluded that the mechanisms of the cerebral metabolic effects of halothane differ from those of thiopental and, at high concentrations, are at least in part related to interference with oxidative phosphorylation. These in vivo studies confirm the potentially detrimental effects of high halothane concentrations on cerebral metabolic pathways as demonstrated by others in vitro.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005112:Extracorporeal Circulation; D005947:Glucose / Q000378:metabolism; D006221:Halothane / Q000008:administration & dosage / Q000633:toxicity*; D007773:Lactates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013874:Thiopental / Q000633:toxicity; D014655:Vascular Resistance / Q000187:drug effects
D007773:Lactates; D011773:Pyruvates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005947:Glucose; D013874:Thiopental; D006221:Halothane