Endotoxin shock: thermoregulatory mechanisms

To clarify mechanisms of hypothermia in lipopolysaccharide (LPS) shock, four experiments were conducted in 72 chronically instrumented Wistar rats. They were intended to accomplish the following: experiment 1, determine the dose of intravenous Escherichia coli LPS that induces a body temperature (Tb) fall at a minimal mortality the dose chosen (0.5 mg/kg) was then used in experiments 2-4; experiment 2, identify the time course of the arterial blood pressure (BP) fall (shock) during the response to LPS; experiment 3, measure threshold Tb values for skin vasodilation and activation of metabolic heat production (M) during the LPS shock; and experiment 4, ascertain behavioral thermoregulation in LPS shock. For experiments 1-3, rats were kept in restrainers; ambient temperature (Ta) was 26 degrees C. In experiment 4, rats freely moved in a thermogradient (18-33 degrees C). Variables monitored were colonic (Tc) and tail skin (Tsk) temperatures (experiment 1); BP (experiment 2); hypothalamic temperature (Thy), M (from oxygen consumption), and Tsk (experiment 3); and preferred Ta (Tpr) and abdominal temperature (experiment 4). In experiment 1, LPS induced no Tc changes at 0 mg/kg, a biphasic fever (no mortality) at 0.05 mg/kg, a biphasic hypothermia (42% mortality) at 0.5 mg/kg, and a rapid fall of Tc (100% mortality) at 5 mg/kg. LPS-induced (0.5 mg/kg) hypotension (experiment 2) occurred simultaneously with the first hypothermic phase; both Tc and BP reached their nadirs (-0.8 +/- 0.1 degrees C and -34 +/- 12 mmHg) at approximately 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 (experiment 3; P < 0.05). In experiment 4, 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.