Endotoxin shock: thermoregulatory mechanisms.
Romanovsky, Andrej A., Osamu Shido, Sohtaro Sakurada, Naotoshi
Sugimoto, and Tetsuo Nagasaka.
Department of Physiology, Kanazawa University Medical School,
Kanazawa 920, Japan
APStracts 2:0292R, 1995.
To clarify mechanisms of hypothermia in lipopolysaccharide (LPS)
shock, four experiments (E1-E4) were conducted in 72 chronically
instrumented Wistar rats. They were aimed at: E1 determining the dose
of iv E. coli LPS that induces a body temperature (Tb) fall at a
minimal mortality [the dose chosen (0.5 mg/kg) was then used in E2
-E4]; E2 identifying the time course of the arterial blood pressure
(BP) fall (shock) during the response to LPS; E3 measuring threshold
Tbs for skin vasodilation and activation of metabolic heat production
(M) during the LPS-shock; and E4 ascertaining behavioral
thermoregulation in LPS-shock. For E1-E3, rats were kept in
restrainers; ambient temperature (Ta) was 26 degrees C. In E4, rats
freely moved in a thermogradient (18 33 degrees C). Variables
monitored were: colonic (Tc) and tail skin (Tsk) temperatures (E1);
BP (E2); hypothalamic temperature (Thy), M (from VO2), and Tsk (E3);
and preferred Ta (Tpr) and abdominal temperature (E4). In E1, LPS
induced: at 0 mg/kg no Tc changes; at 0.05 mg/kg a biphasic fever (no
mortality); at 0.5 mg/kg a biphasic hypothermia (42% mortality); and
at 5 mg/kg a rapid fall of Tc (100% mortality). LPS (0.5 mg/kg)
induced hypotension (E2) occurred simultaneously with the first
hypothermic phase; both Tc and BP reached their nadirs ( 0.8 +/- 0.1
degrees C and 34 +/- 12 mm Hg) at _1.5 h post-LPS. The major
autonomic mechanism of the shock hypothermia was a shift in the
threshold Thy for M from 37.9 +/- 0.3 to 36.0 +/- 0.3 degrees C (E3;
P < 0.05). In E4, rats selected Tpr below 25 degrees C (vs. 28-30
degrees C in control; P < 0.05) throughout the duration of the shock;
their Tb dropped to 36.2 +/- 0.3 degrees C (P < 0.05). In sum, the
LPS shock-associated hypothermia involves a decrease in the threshold
Tb for M, the resultant widening of the interthreshold zone, and
cold-seeking behavior.
Received 26 June 1995; accepted in final form 18 October 1995.
APS Manuscript Number R394-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 November 95