Biomedical subjects
Publications and source records attributed to O Shido.
In sum, our results indicate that LPS shock-associated hypothermia involves the following major mechanisms: 1) a decrease in the threshold Tb for activation of cold thermogenesis; 2) the resultant widening of the interthreshold zone; and 3) cold-seeking behavior. We speculate that, in severe systemic inflammation, this hypothermia constitutes an adaptive response.
Several timed daily environmental cues alter the pattern of nycthemeral variations in body core temperature in rodents. The present study investigated the effect of timed exercise on variations of daily body core temperature. Male rats were housed in cages with a running wheel at an ambient temperature of 24 degrees C with a 12:12 h light/dark cycle. Timed daily exercise rats (TEX) were allowed access to the wheel for 6 h in the last half of the dark phase, freely exercising rats (FEX) could run at any time, and sedentary rats (NEX) were not allowed to run. After a 3-week exercise period, all animals were denied access to the wheel. The intraabdominal temperatures (Tab) and spontaneous activities of rats were measured for 6 days after the exercise period. The Tab values of the TEX rats were significantly higher than those of the other two groups only in the last half of the dark phase, while Tab in the FEX and NEX rats showed no significant difference. The specific Tab changes in the TEX rats lasted for 2 days after the exercise period. Spontaneous activity levels were higher in the TEX rats than the FEX and NEX rats in the last half of the dark phase for 1 day after the exercise period. The results suggest that daily exercised limited to a fixed time per day modifies nycthemeral variations of body core temperature in rats so that the temperature increases during the period when the animals had previously exercised. Such a rise in body core temperature is partly attributed to an increase in the spontaneous activity level.
We studied the effect of an abdominal prick with a needle on LPS-induced fever in freely-moving rats. LPS was injected intraperitoneally by the following 3 methods: 1) through a hypodermic needle pricked into the abdominal cavity, 2) through a catheter chronically indwelt in the abdominal cavity, and 3) through a catheter chronically indwelt in the abdominal cavity immediately after an abdominal prick was made. In the second method, core body temperature (Tb) began to rise about 1 h after the injection, reaching a maximal level at around 2.5 h and decreasing gradually thereafter. In the first and third methods, Tb rose again to make a second peak after making the first peak of fever. This was the same when LPS was injected through a hypodermic needle pricked into the abdominal cavity under restrained condition. These results suggest that the abdominal prick with a needle is responsible for the development of the second peak (or prolongation) of LPS-fever in rats.
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.
This study investigated the day-night differences in behavioral and autonomic thermoregulatory responses to bacterial lipopolysaccharide (LPS) in rats. Male rats were housed individually in cages with a 12: 12 h light dark cycle at an ambient temperature of 24 degrees C. The rats were placed in a box with a temperature gradient and intraperitoneally injected with LPS (10 micrograms/kg). The preferred ambient temperature (Tpr) was estimated by the location of the rats in the box, and intraperitoneal temperature (Tb) was measured by a biotelemetry system. Measurements were taken during the light and dark phases of the day. LPS produced fever in both phases. The magnitude of rise in Tb did not differ between the two periods. In the dark phase, Tpr significantly increased during the development of fever and decreased during the defervescence, while it did not change throughout the febrile course during the light phase. In a separate experiment, rats were loosely restrained and placed in a direct calorimeter. Their colonic temperature (Tcol), evaporative and nonevaporative heat loss and heat production were measured before and after intraperitoneal injections of LPS (10 micrograms/kg). Measurements were taken during the light and dark phases of the day. LPS induced fever in both phases. The magnitude of change in T col, heat loss, and heat production due to LPS did not differ between the two periods. These results suggest that the fertile response of rats to intraperitoneal LPS is not affected by the time of day. However, it seems that during LPS-induced fever, thermoregulatory behavior is not fully activated during the light phase of the day.
1. Heat-acclimated (HA) rats, kept under a 12:12 h light-dark regime, were subjected to an ambient temperature (Ta) of 33 degrees C for 5 h in the last half of the dark phase for 3 weeks. Control rats were kept under a 12:12 h light-dark regime at a constant Ta of 24 degrees C. 2. After the acclimation period, the rats were then placed in a metabolic chamber at a Ta of 26.5 degrees C, and body core temperature was gradually increased and decreased using an intravenous thermode. Thermoeffector thresholds were determined by the hypothalamic temperature (T(hy)) at the onset of warm-induced tail skin vasodilatation and cold-induced thermogenesis measured by oxygen consumption. 3. Each rat was subjected to the experiment twice, once in the first half and once in the last half of the dark phase, on different days in random order. 4. In HA rats, T(hy) at the onset of both skin vasodilatation and thermogenesis were significantly lower in the last half of the dark phase compared with the first half. In control rats, however, there were no such differences between the two halves. 5. The results suggest that in rats acclimated to daily heat exposure, thermoeffector thresholds shift to lower temperatures only during the period of day when the rats had previously been exposed to heat.
The expression of Fos protein in the rat diencephalon, brain stem, cerebellum, and spinal cord was investigated using immunohistochemistry during chronic cold exposure, in order to clarify the neural regions involved in the thermoregulatory responses and the central mechanism of neural activation with cold acclimation. Numerous Fos-positive cells were observed in many brain regions after cold exposure and changes in the number of Fos-positive cells were analyzed quantitatively. Fos-positive regions were classified into three groups on the basis of the expression period of Fos protein. The first group was where a significant number of Fos-positive cells were seen 3 h and 24 h after cold exposure, but not observed 14 days after exposure; the regions included the lateral septal nucleus (LS), parvocellular paraventricular hypothalamic nucleus (pPVN), posterior hypothalamic area (PH), supramammillary nucleus (SuM), locus coeruleus (LC), dorsal tegmental nucleus (DTg), vestibular nucleus (Ves), and nucleus of solitary tract (Sol). The second group was where a significant number of Fos-positive cells were found 3 h, 24 h and 14 days after cold exposure; the regions included the preoptic hypothalamic area (POA), paraventricular thalamic nucleus (PV), lateral preoptic area (LPO), zona incerta (ZI), subparafascicular thalamic nucleus (SPF), lateral dorsal central grey (CGLD), lateral ventral central grey (CGLV), microcellular tegmental nucleus (MiTg), lateral lemniscus nucleus (LL), dorsal parabrachial nucleus (DPB), and the cerebellum. The third group was where Fos-positive cells were more numerous 14 days after cold exposure than they were after 3 h and 24 h of exposure; these regions included the ventromedial hypothalamic nucleus (VMH) and the spinal cord. These results demonstrate that the numbers and regions of Fos-positive cells in the rat brains changed during chronic cold exposure, and such changes may reveal the cellular adaptation of the thermogenic responsive neurons in the rat brain to cold acclimation.
Fos expression in the rat diencephalon, brain stem, cerebellum, and spinal cord was examined after warm (33 degrees C) and cold (10 degrees C) ambient exposures. Fos expression was examined with use of immunohistochemical method and the number of Fos-positive neurons in each nucleus was quantitatively analyzed. When rats were exposed to cold ambient, significant number of Fos-positive neurons was found in the lateral septal nucleus (LS), preoptic hypothalamic area (POA), parvocellular paraventricular hypothalamic nucleus (pPVN), lateral preoptic area (LPO), zona incerta (ZI), paraventricular thalamic nucleus (PV), ventromedial hypothalamic nucleus (VMH), subparafascicular thalamic nucleus (SPF), posterior hypothalamic area (PH), supramammillary nucleus (SuM), microcellular tegmental nucleus (MiTg), lateral lemniscus nucleus (LL), lateral dorsal central grey (CGLD), lateral ventral central grey (CGLV), dorsal parabrachial nucleus (DPB), locus coeruleus (LC), dorsal tegmental nucleus (DTg), vestibular nucleus (Ves), nucleus of solitary tract (Sol), spinal cord, and cerebellum. When animals were exposed to warm ambient, the numbers of Fos-positive neurons in the LS, POA, PV, LPO, and SuM were significantly increased to be equal to those of cold ambient. However, after warm ambient exposure the numbers of Fos-positive neurons in the DPB and spinal cord were increased but less than those of cold ambient, and those in the pPVN, VMH, ZI, SPF, PH, CGLD, CGLV, MiTg, LL, LC, DTg, Ves, Sol, and cerebellum were not significantly increased as compared with those of control or cold ambient. Abdominal temperature was not changed during cold ambient exposure, but the temperature was significantly increased during warm ambient exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was performed to investigate the mechanism of heat-induced vasoconstriction (HIVC) in human fingers. The left fingers of five male subjects were immersed in water controlled at an initial temperature of 35.0 degrees C. The blood flows (BF) of the left index and fourth fingers were measured continuously with laser-Doppler flowmeter probes, and the temperatures of the middle finger and water bath were also monitored continuously using thermistor probes. Arterial blood pressure and heart rate were measured every minute before and during local finger warming. A local anesthetic (0.5% bupivacaine hydrochloride) or saline at a volume of 5.0-8.0 ml was aseptically injected into the base of the fourth or index finger, respectively. After finger BFs had been stabilized for > or = 10 min, the fingers were warmed by raising the water bath temperature from 35.0 to 41.5 degrees C in 14 min. The BF of the index finger fell significantly for 6 min after local warming was commenced (at water bath temperatures between 35.5 and 37.5 degrees C) without associated changes in mean arterial blood pressure, indicating the occurrence of HIVC. Then BF increased toward prewarming levels. The local anesthetic injection, however, completely abolished HIVC in the fourth finger. These results suggest that, in humans, innervation to finger vessels is indispensable for producing HIVC and hence that a local mechanism, such as myogenic vascular response to high temperature, may not be involved in the induction of HIVC.
Body core temperature of rats acclimated to heat given daily at a fixed time falls during the previous heat exposure time. In the present study, thermoregulatory responses of heat-acclimated rats were examined during the specific period. Heat-acclimated rats were subjected to an ambient temperature of 32 degrees C for approximately 5 h in the first half or last half of the dark phase for 14 days while control rats were kept at 24 degrees C. Then the rats were placed in a direct calorimeter and were warmed for 30 min with an intraperitoneal electric heater. Measurements were made twice in the first and last halves of the dark phase. Body warming significantly increased body core temperature in all rats. In the heat-acclimated rats, heat production (M) was significantly depressed during the previous heat exposure time but not during the other period. Body warming had little effect on M in the control rats during either period. The results suggest that rats acclimated to heat given at a fixed time daily respond to an acute heat load with a pronounced reduction of M. However, such a response was observed only during the period when the rats had been previously exposed to heat.
Rats were subjected to an ambient temperature (Ta) of 33 degrees C for ca. 5 h during the last half of the dark phase for 5, 14 or 28 consecutive days (heat-exposed rats, HE), while control rats were kept at a constant Ta of 24 degrees C. After the heat exposure schedule, the levels of hypothalamic temperature (T(hy)) as an index of body core temperature in the HE were significantly lower than those of the controls for 2-4 h in the last half of the dark phase. The low levels of T(hy) persisted during the specific period for 1, 3 and 6 days after the end of the 5-, 14- and 28-day heat exposure schedules, respectively. These results confirm that, in rats subjected to daily heat exposure for ca. 5 h at a fixed time per day, their T(hy) falls during the period when the rats were previously exposed to heat, and suggest that the duration of the specific T(hy) change observed after completing the heat exposure schedule depends on the length of the heat exposure schedule.
Changes in body core temperature (T(cor)) and heat balance after an abrupt release of lower body negative pressure (LBNP) were investigated in 5 volunteers under the following conditions: (1) an ambient temperature (Ta) of 20 degrees C or (2) 35 degrees C, and (3) Ta of 25 degrees C with a leg skin temperature of 30 degrees C or (4) 35 degrees C. The leg skin temperature was controlled with water perfusion devices wound around the legs. Rectal (T(re)), tympanic (T(ty)) and esophageal (T(es)) temperatures, skin temperatures (7 sites) and oxygen consumption were measured. The intensity of LBNP was adjusted so that the amount of blood pooled in the legs was the same under all conditions. When a thermal balance was attained during LBNP, application of LBNP was suddenly halted. The skin temperatures increased significantly after the release of LBNP under all conditions, while oxygen consumption hardly changed. The release of LBNP caused significant falls in T(cor)s under conditions (1) and (3), but lowered T(cor)s very slightly under conditions (2) and (4). The changes in T(es) were always more rapid and greater than those of T(ty) and T(re). The falls in T(ty) and T(re) appeared to be explained by changes in heat balance, whereas the sharp drop of T(es) could not be explained especially during the first 8 min after the release of LBNP. The results suggest that a fall in T(cor) after a release of LBNP is attributed to an increase in heat loss due to reflexive skin vasodilation and is dependent on the temperature of venous blood returning from the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)
Male Wistar rats were divided into two groups. The controls (CN) were kept at a constant ambient temperature (Ta) of 24 degrees C throughout the experiment. Heat-acclimated rats (HA) were subjected to Ta of 33 degrees C in the last half of the dark phase for 16 consecutive days. After the schedule was terminated, hypothalamic temperature (Thy), oxygen consumption (VO2), heat loss, and feeding activity were measured for the following 2 days at Ta of 24 degrees C with a direct calorimeter in constant darkness. Hypothalamic temperature, VO2, and heat loss of the HA were significantly lower than those of the CN for 3-4 h during the period when the rats had been previously exposed to heat. Feeding activity during the specific period was significantly less in the HA than in the CN only on the first day. Under starved conditions, the decreases of Thy and VO2 during the previous heat exposure time were consistent in the HA. The results suggest that body core temperature and feeding behavior decrease during the previous heat exposure time in rats after subjection to repeated heat exposure at a fixed time daily. The characteristic fall in body core temperature is mainly attributed to the reduction of VO2. It also seems that a decrease in postprandial thermogenesis is not a predominant contributor to the depression of VO2 during the previous heat exposure time in heat-acclimated rats.
We have previously shown that the febrile response of guinea pigs to lipopolysaccharide (LPS) is attenuated by the subcutaneous administration of the tertiary mu-receptor opioid antagonist naloxone-hydrochloride (Nal-HCl). Because Nal-HCl readily crosses the blood-brain barrier (BBB), this study was undertaken to investigate whether its effect on fever is mediated peripherally or centrally. For this, the effects of 1) Nal-HCl (23 and 46 mumol/kg sc), 2) the quaternary opioid antagonists Nal-methiodide (Nal-mI, 46 and 92 mumol/kg sc) and Nal-methobromide (Nal-mBr, 92 mumol/kg sc), which do not cross the BBB, and 3) intracerebroventricular Nal-HCl (0.25 and 1.25 mumol) on the febrile response to intravenous S. enteritidis LPS (2 micrograms/kg) were investigated in conscious guinea pigs. Under afebrile conditions, both Nal-HCl (whether administered sc or icv) and its quaternary analogues induced hypothermic responses. Peripheral Nal-HCl, Nal-mI, and Nal-mBr also attenuated both phases of the characteristically biphasic LPS fever. The thermal effects of the peripheral opioid antagonists, both tertiary and quaternary, were associated with cutaneous vasodilation. Intracerebroventricularly administered Nal-HCl did not evoke any attenuation of fever. The analysis of the data shows that Nal-HCl possesses three different thermoregulatory actions: a central hypothermic action, a peripheral thermolytic action (which is due to, at least partly, cutaneous vasodilation), and a peripheral antipyretic action. The latter effect suggests that, in guinea pigs, circulating opioids may have a role in fever production.
Male Wistar rats were acclimated to cages with running wheels. Then, the running time of rats were limited to the last 3 (WR3) or 6 (WR6) h of the dark phase. After a 2-week activity restriction, the rats were again allowed access to the wheel freely. In the WR3 or WR6, wheel revolutions for the last 3 or 6 h of the dark phase was significantly greater after the activity restriction than before. The results suggest that, in rats, voluntary running limited to a fixed time daily alters the distributions of locomotor activity in a day, i.e., running activity increases during the period when the rats had been previously allowed to exercise.
Intrapreoptic (IPO) microinjections of various agents cause unavoidable brain tissue injury, often resulting in prostaglandin (PG)-mediated core temperature (Tc) rises. However, IPO microinjection of the alpha 2-adrenoreceptor agonist clonidine (Clo) generally evokes a Tc fall, seemingly avoiding the influence of injury due to the microinjection procedure per se. To clarify this, we microinjected bilaterally into the preoptic/anterior hypothalamus of conscious guinea pigs various doses of Clo dissolved in pyrogen-free saline (PFS, 1 microliter/side). Clo caused biphasic hypo-/hyperthermic responses. The initial hypothermia was dose dependent: no decrease in Tc for 0.1 microgram of Clo, -0.4 +/- 0.1 degree C for 0.5 microgram, -0.9 +/- 0.1 degree C for 1.5 microgram, and -1.2 +/- 0.1 degree C for 5.0 micrograms. During the hyperthermic phase, Tc increased to a dose-independent level (1.0-1.5 degrees C), remaining there up to 5 h postinjection. PFS microinjected IPO also induced hyperthermia, but without any initial Tc decrease. This Tc rise was delayed by 100 min when the cyclooxygenase inhibitor indomethacin (Indo, 50 micrograms/microliters) was injected. Nontreated animals (time controls) maintained Tc at baseline levels during the whole experiment. The alpha 2-antagonist rauwolscine (2 micrograms/side), microinjected IPO 10 min before Clo (0.5 microgram/side), abolished the hypothermic without affecting the hyperthermic response phase; Indo (10 mg/kg), injected intramuscularly 20 min after the IPO microinjection of Clo (0.5 microgram), significantly attenuated the hyperthermic phase. These results confirm that an artifactitious, PG-mediated Tc rise consequent to nonspecific brain tissue injury contaminates the thermal response to agents (hyper- or hypothermizing) microinjected IPO.(ABSTRACT TRUNCATED AT 250 WORDS)
Male Wistar rats were divided into five groups: a control group kept at an ambient temperature of 24 degrees C for 14 days, and four heat-acclimated groups (two groups subjected to a constant ambient temperature of 33 degrees C for 4 days or 14 days (HC-14) immediately preceding the measurement; and another two groups subjected to an ambient temperature of 33 degrees C for about 5 h once a day for 4 days, or 14 days (HI-14) just prior to the measurement). After the completion of the schedule, the rats were placed in a temperature-controlled chamber. Hypothalamic (Thy) and interscapular brown adipose tissue (TBAT) temperatures, oxygen consumption (VO2), and shivering activity were measured during a gradual fall in temperature of a water jacket surrounding the chamber (TW) from 30 to 10 degrees C at a constant rate of 0.18 degree C/min. During the fall in TW, VO2 and TBAT increased significantly and shivering was induced without associate changes in Thy in all groups. TW at the onset of a rise in metabolic heat production (onset of cold-induced thermogenesis) coincided with that at the onset of a rise in TBAT (onset of BAT thermogenesis), but was significantly higher than that at the onset of shivering. In HC-14 and HI-14 rats, TWS at the onset of cold-induced thermogenesis and BAT thermogenesis were significantly higher than those in control rats, whereas TWS at the onset of shivering were not different from those in control rats. The onset of cold-induced thermogenesis did not change after the 4-day heat exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was conducted to investigate day-night variations of plasma thyroid hormone and energy substrate levels in rats after acclimation to heat loaded for several hours at a fixed time per day. The heat-acclimated rats were exposed to an ambient temperature of 33 degrees C for 5 h in the last half of the dark phase for 16 consecutive days, while the control rats were kept at 24 degrees C for the same period. After completing the schedule, plasma levels of triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4), cortisol, triglyceride, nonesterified fatty acid, total protein, and glucose were measured at 3-h intervals between 00:00 and 18:00 (dark phase, 03:00-15:00). The plasma levels of T3 and FT3 of the heat-acclimated rats were higher than those of the controls in the last half of the dark phase. Similar differences were observed for T4 and FT4 levels. The plasma cortisol level was consistently higher in the heat-acclimated rats than in the control rats. There were no particular differences in energy-substrate levels between the two groups at any time of the day. These results indicate that heat exposure at a fixed time per day alters the pattern of day-night variations of plasma thyroid hormone levels in rats. It is noteworthy that the plasma levels of thyroid hormones, especially T3 and FT3, increased during the period when the rats had been previously exposed to heat.