Romanovsky A A, Shido O, Sakurada S, Sugimoto N, Nagasaka T
Department of Physiology, Kanazawa University Medical School, Japan.
Am J Physiol. 1996 Apr;270(4 Pt 2):R693-703. doi: 10.1152/ajpregu.1996.270.4.R693.
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.
为阐明脂多糖（LPS）休克时体温过低的机制，在72只长期植入仪器的Wistar大鼠身上进行了四项实验。这些实验旨在实现以下目标：实验1，确定能以最低死亡率诱导体温（Tb）下降的静脉注射大肠杆菌LPS剂量[然后将选定的剂量（0.5mg/kg）用于实验2-4]；实验2，确定对LPS反应过程中动脉血压（BP）下降（休克）的时间进程；实验3，测量LPS休克期间皮肤血管舒张和代谢产热（M）激活的阈值Tb值；实验4，确定LPS休克时的行为体温调节。对于实验1-3，大鼠被置于约束器中；环境温度（Ta）为26℃。在实验4中，大鼠在温度梯度（18-33℃）中自由活动。监测的变量有结肠温度（Tc）和尾部皮肤温度（Tsk）（实验1）；血压（BP）（实验2）；下丘脑温度（Thy）、M（根据耗氧量）和Tsk（实验3）；以及偏好的Ta（Tpr）和腹部温度（实验4）。在实验1中，0mg/kg的LPS未引起Tc变化，0.05mg/kg时出现双相热（无死亡），0.5mg/kg时出现双相体温过低（死亡率42%），5mg/kg时Tc迅速下降（死亡率100%）。LPS诱导的（0.5mg/kg）低血压（实验2）与第一个体温过低阶段同时发生；LPS注射后约1.5小时，Tc和BP均达到最低点（-0.8±0.1℃和-34±12mmHg）。休克性体温过低的主要自主神经机制是M的阈值Thy从37.9±0.3℃转变为36.0±0.3℃（实验3；P<0.05）。在实验4中，在整个休克期间，大鼠选择的Tpr低于25℃（与对照组的28-30℃相比；P<0.05）；它们的Tb降至36.2±0.3℃（P<0.05）。总之，LPS休克相关的体温过低涉及M的阈值Tb降低、由此导致的阈值间区域变宽以及寻冷行为。
