Is lactate a mediator of hypoxia-induced anapyrexia?

Abstract

Hypoxia causes a regulated decrease in body core temperature ( T(c)), termed anapyrexia, which seems to be a very effective way of preventing hypoxia-associated cell damage. Since during several pathological states the supply of O(2) is a limiting factor, the clinical importance of anapyrexia is evident. However, the mechanisms involved in this response remain unclear. We tested the hypothesis that lactate, a classic companion of hypoxia, is a mediator of hypoxia-induced anapyrexia, using the inhibitor of acid lactic production dichloroacetate (DCA). Each of 28 rats was placed in a chamber ventilated with humidified air at an ambient temperature of 24-26 degrees C. After a control period of 30 min the animals were given saline or 100 mg/kg DCA i.p. Then, 30 min later, the chamber was flushed with a 7% O(2) gas mixture for 2 h. At the end of the experiment, the animals were decapitated and blood samples collected for measurements of plasma lactate. T(c) was measured by biotelemetry. DCA did not affect the T(c) or basal lactate levels of normoxic rats. Hypoxia elicited a significant decrease in T(c) and an increase in plasma lactate levels. Although DCA decreased plasma lactate levels during hypoxia, it caused no change in the course of hypoxia-induced anapyrexia. Correspondingly, no correlation was found between the drop in T(c) and the rise in plasma lactate during hypoxic conditions. These results do not support the hypothesis that lactate is a mediator of hypoxia-induced anapyrexia in rats.