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 O₂ 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 °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% O₂ 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.