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Department of Physiology and Biophysics, University of Tennessee at Memphis, Memphis, Tennessee 38163; and Thermoregulation Laboratory, Legacy Research, Legacy Portland Hospitals, Portland, Oregon 97227
Received 26 February 1996; accepted in final form 19 August 1996.
Romanovsky, Andrej A., and Clark M. Blatteis. Heat
stroke: opioid-mediated mechanisms. J. Appl.
Physiol. 81(6): 2565-2570, 1996.
In our previous
study in guinea pigs, intensive and prolonged intraperitoneal heating
(IPH) caused heat stroke characterized by high mortality and
accompanied by two paradoxical phenomena: ear skin vasoconstriction at
a high body temperature (Tb)
(hyperthermia-induced vasoconstriction) and a post-IPH
Tb fall at an ambient temperature (Ta) below thermoneutrality
(hyperthermia-induced hypothermia). In this study, we tested the
hypothesis that the mechanisms of the two phenomena involve endogenous
opioid agonists. Experiments were conducted in 24 unanesthetized,
lightly restrained guinea pigs, each chronically implanted with an
intraperitoneal thermode and intrahypothalamic thermocouple. The
thermoregulatory effects of a wide-spectrum opioid-receptor antagonist,
naltrexone (NTX; 50 or 0 µmol/kg sc), were studied in IPH-induced
heat stroke and under normal conditions. IPH was accomplished by
perfusing (50 ml/min; 80 min) water (45°C) through the thermode.
Ta was maintained at ~24°C.
Skin vasodilation occurred at the onset of IPH but later changed to
vasoconstriction despite high Tb
and continuing IPH. IPH-induced hyperthermia (1.8 ± 0.1°C) was followed by a post-IPH Tb fall (
5.1 ± 0.7°C; calculated for the survivors only). The 48-h mortality rate
was 50%. NTX prevented the hyperthermia-induced vasoconstriction and
attenuated the hyperthermia-induced hypothermia (1.8 ± 0.4°C). None of the NTX-treated animals died. The effects of NTX on
Tb regulation under normal
conditions were minor. These results indicate that the phenomena of
both hyperthermia-induced vasoconstriction and hyperthermia-induced
hypothermia are opioid dependent. The latter is speculated to reflect
opioid-mediated inhibition of metabolism; the former is thought to
result from opioid-induced hemodynamic alterations. Because both
phenomena did not occur in the NTX-treated survivors, the skin
vasoconstriction at high Tb and
the posthyperthermia Tb fall may
be viewed as markers of the severity of heat stroke. It is suggested
that opioid antagonists may have therapeutic potential in heat-induced
disorders.
hyperthermia; hypothermia; poikilothermia; vasoconstriction; vasodilation
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