Effect of subdiaphragmatic vagotomy on the noradrenergic and HPA axis activation induced by intraperitoneal interleukin-1 administration in rats. (49/200)

The vagus nerve is thought to participate in signal transduction from the immune system to the CNS. The role of the vagus in the physiological, behavioral and neurochemical responses to intraperitoneally (ip) injected interleukin-1beta (IL-1beta) was studied using awake subdiaphragmatically vagotomized rats. The rats were injected ip with saline and IL-1beta (1 microg/rat) in random order. For the next 2-4 h, they were monitored for locomotor activity, body temperature via abdominally implanted telethermometers, hypothalamic norepinephrine (NE) secretion using in vivo microdialysis and blood sampled via intravenous catheters to determine concentrations of ACTH and corticosterone to assess hypothalamo-pituitary-adrenocortical (HPA) axis activation. Saline injections were followed by transient increases in locomotor activity, body temperature, dialysate NE and plasma concentrations of ACTH and corticosterone. These responses were not significantly altered by vagotomy. IL-1beta injections resulted in short-lived increases in shivering and longer decreases in locomotor activity, as well as a delayed modest fever. IL-1beta also induced prolonged elevations of hypothalamic microdialysate NE, as well as plasma ACTH and corticosterone. Similar responses were observed regardless of the order of the saline and IL-1beta injections. Subdiaphragmatic vagotomy prevented the IL-1-induced increases in body temperature and the increase in dialysate NE, and markedly attenuated the increases in plasma ACTH and corticosterone. The results indicate close temporal relationships between the apparent release of NE and the increase in body temperature and the HPA activation. This together with the effects of vagotomy suggests that the activation of NE in turn increases body temperature and activates the HPA axis. However, because IL-1beta induces a limited HPA activation in subdiaphragmatically vagotomized rats, the vagus nerve does not appear to be the only route by which ip IL-1beta can activate the HPA axis. It is suggested that IL-1beta-induced vagal activation of hypothalamic NE is the major mechanism of HPA activation at low doses of IL-1beta. However, IL-1beta can also exert direct effects on IL-1 receptors on cerebral blood vessels, activating cyclooxygenases and hence synthesis of prostaglandins which in turn can affect body temperature, behavior and HPA axis activation.  (+info)

Fatty acid transport protein 1 is required for nonshivering thermogenesis in brown adipose tissue. (50/200)

Nonshivering thermogenesis in brown adipose tissue (BAT) generates heat through the uncoupling of mitochondrial beta-oxidation from ATP production. The principal energy source for this process is fatty acids that are either synthesized de novo in BAT or are imported from circulation. How uptake of fatty acids is mediated and regulated has remained unclear. Here, we show that fatty acid transport protein (FATP)1 is expressed on the plasma membrane of BAT and is upregulated in response to cold stimuli, concomitant with an increase in the rate of fatty acid uptake. In FATP1-null animals, basal fatty acid uptake is reduced and remains unchanged following cold exposure. As a consequence, FATP1 knockout (KO) animals display smaller lipid droplets in BAT and fail to defend their core body temperature at 4 degrees C, despite elevated serum free fatty acid levels. Similarly, FATP1 is expressed by the BAT-derived cell line HIB-1B upon differentiation, and both fatty acid uptake and FATP1 protein levels are rapidly elevated following isoproterenol stimulation. Stimulation of fatty uptake by isoproterenol required both protein kinase A and mitogen-activated kinase signaling and is completely dependent on FATP1 expression, as small-hairpin RNA-mediated knock down of FATP1 abrogated the effect.  (+info)

Nalfurafine, the kappa opioid agonist, inhibits icilin-induced wet-dog shakes in rats and antagonizes glutamate release in the dorsal striatum. (51/200)

Icilin, a cooling compound, produces vigorous wet-dog shakes in rats. We have reported previously that icilin-induced wet-dog shakes are blocked by the kappa opioid receptor agonists, nalfurafine and U50,488H, and that icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum. Since activation of kappa opioid receptors inhibits glutamate release intrastriatally, we targeted glutamate release within the dorsal striatum using nalfurafine and examined the role of the dorsal striatum in icilin-induced wet-dog shakes, more specifically, the effect that icilin-evoked intrastriatal glutamate release has on the overt stimulant behavior. We report that nalfurafine (0.04mg/kg) inhibits icilin (0.50mg/kg)-induced wet-dog shakes and that this inhibition is reversed by intrastriatal perfusion of the kappa opioid receptor antagonist, norbinaltorphimine (100nM). Furthermore,we antagonized icilin-evoked glutamate release with nalfurafine (0.04mg/kg), and reversed inhibition of glutamate release with intrastriatal norbinaltorphimine (100nM). These findings support a central component in the behavioral response to icilin and suggest that activation of kappa opioid receptors antagonizes icilin-induced wet-dog shakes in rats by inhibiting glutamate release within the dorsal striatum.  (+info)

Oxygen uptake during recovery following naloxone. Relationship with intraoperative heat loss. (52/200)

The increased metabolic and respiratory demand during naloxone recovery from opioid-based anesthesia could be related to the return of thermoregulation in hypothermic patients and thus be avoided by preventing intraoperative hypothermia. In this study, we measured O2 uptake (VO2) during naloxone-induced recovery in two groups of patients to determine the effect of intraoperative heat loss on postoperative VO2 changes. In seven patients, intraoperative hypothermia was prevented (normothermic group), whereas hypothermia was allowed to develop in seven other patients (hypothermic group). Core and skin temperatures were measured throughout the study to calculate changes in body heat content. Before naloxone antagonism of fentanyl-supplemented anesthesia, core temperature (mean +/- SEM) was 36.8 +/- 0.1 degrees C in the normothermic group and 34.2 +/- 0.2 degrees C in the hypothermic group (P less than 0.001). After titrated administration of naloxone during recovery, VO2 and minute ventilation (VE) increased in the hypothermic group, by 114 +/- 37% and 97 +/- 52% respectively (P less than 0.05), with a three-fold increase in four patients. In the normothermic group, VO2 increased significantly less (25 +/- 5%), without any significant change in VE. The change in VO2 and VE was significantly greater in patients who were hypothermic. VO2 was integrated throughout the recovery period to calculate recovery energy expenditure. Recovery energy expenditure and intraoperative heat loss were highly correlated (r = 0.88; P less than 0.01). This study demonstrates that the metabolic and respiratory stresses associated with naloxone-induced recovery from opioid-based anesthesia depend on the intraoperative heat loss and can therefore be reduced by preventing intraoperative hypothermia.  (+info)

Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study. (53/200)

INTRODUCTION: Mild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions-vasoconstriction and shivering-which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34 degrees C without producing significant sedation or respiratory depression. METHODS: Eight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 mug/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 mug/ml). Volunteers were cooled with 4 degrees C cold Ringer lactate infused over a central venous catheter (rate asymptotically equal to 2.4 degrees C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale. RESULTS: Control shivering threshold was 35.5 degrees C +/- 0.2 degrees C. Skin warming reduced the shivering threshold to 34.9 degrees C +/- 0.5 degrees C (p = 0.01). Meperidine reduced the shivering threshold to 34.2 degrees C +/- 0.3 degrees C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days. CONCLUSION: A combination of meperidine and skin surface warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C via an additive interaction and produced only very mild sedation and no respiratory toxicity.  (+info)

Lipid mobilization of long-distance migrant birds in vivo: the high lipolytic rate of ruff sandpipers is not stimulated during shivering. (54/200)

For long migrations, birds must rely on high flux capacities at all steps of lipid metabolism, from the mobilization of adipose reserves to fatty acid oxidation in flight muscle mitochondria. Substrate kinetics and indirect calorimetry were used to investigate key parameters of lipid metabolism in a highly aerobic shorebird: the ruff sandpiper Philomachus pugnax. In this study, we have quantified the effects of cold exposure because such measurements are presently impossible during flight. Lipolytic rate was monitored by continuous infusion of 2-[(3)H]-glycerol and lipid oxidation by respirometry. Plasma lipid concentrations (non-esterified fatty acids, neutral lipids and phospholipids) and their fatty acid composition were also measured to assess whether cold exposure causes selective metabolism of specific lipids. Results show that shivering leads to a 47% increase in metabolic rate (44.4+/-3.8 ml O(2)kg(-1) min(-1) to 65.2+/-8.1 ml O(2) kg(-1) min(-1)), almost solely by stimulating lipid oxidation (33.3+/- 3.3 ml O(2) kg(-1) min(-1) to 48.2+/-6.8 ml O(2) kg(-1) min(-1)) because carbohydrate oxidation remains close to 11.5+/- 0.5 ml O(2) kg(-1) min(-1). Sandpipers support an unusually high lipolytic rate of 55-60 micromol glycerol kg(-1) min(-1). Its stimulation above thermoneutral rates is unnecessary during shivering when the birds are still able to re-esterify 50% of released fatty acids. No changes in plasma lipid composition were observed, suggesting that cold exposure does not lead to selective metabolism of particular fatty acids. This study provides the first measurements of lipolytic rate in migrant birds and shows that their capacity for lipid mobilization reaches the highest values measured to date in vertebrates. Extending the limits of conventional lipid metabolism has clearly been necessary to achieve long-distance migrations.  (+info)

Hypothermia in patients with chronic spinal cord injury. (55/200)

DESIGN: Retrospective analysis of medical records. BACKGROUND/OBJECTIVES: To determine frequency and degree of hypothermic episodes in patients with chronic spinal cord injury (SCI). SETTING: Veterans Administration Medical Center. METHODS: Research involved analysis of body temperature records of 50 chronic patients with tetraplegia. All patients were men with a length of injury of 19 +/- 6 years. Mean age was 53 +/- 15 (SD) years. Data were derived from the computerized patient record database system of the Veterans Administration Medical Center. Results were classified into 3 groups: (a) hypothermia (< 95 degrees F), (b) subnormal temperature (< 97.7 degrees F), and normal temperatures (97.7 degrees F to 98.4 degrees F). Body temperature was recorded during hospitalization (minimum duration of 30 days) using an oral probe twice a day. Ambient temperature was controlled by a central air-conditioning system and maintained at 72 degrees F to 74 degrees F. RESULTS: A total of 867 measurements of body temperature were evaluated; normal temperature was recorded 298 times (35%), subnormal temperature was recorded 544 times (63%), and hypothermia was recorded 25 times (3%). There were 15 patients with 30 hypothermic episodes; subnormal temperature was found in all 50 patients from 1 to 47 times. Regression analysis of age and duration of SCI showed a nonsignificant relationship with body temperature. CONCLUSIONS: Our data suggest that patients with tetraplegia after SCI have significant dysfunction of thermoregulation associated with frequent episodes of subnormal body temperature in a normal ambient environment. Further studies are needed to evaluate possible consequences of low temperatures on the general health of patients and to develop preventive interventions.  (+info)

Fueling shivering thermogenesis during passive hypothermic recovery. (56/200)

In humans, the relative importance of oxidative fuels for sustaining shivering during passive hypothermic recovery or rewarming is still unclear. The main goals of this study were 1) to quantify the respective contributions of lipids and carbohydrates (CHO) during passive rewarming and 2) to determine the effects of precooling exercise on the pattern of fuel utilization. With indirect calorimetry methodologies, changes in fuel metabolism were quantified in nonacclimatized adult men shivering to rewarm from moderate hypothermia (core temperature approximately 34.5 degrees C) not following (Con) or following a precooling exercise at 75% (.)Vo(2max) for 15 min (Pre-CE). As hypothermic individuals shiver to normothermia, results showed that CHO dominate at all shivering intensities above 50% Shiv(peak,) while lipids were preferred at lower intensities. This change in the relative importance of CHO and lipids to total heat production was dictated entirely by modulating CHO oxidation rate, which decreased by as much as 10-fold from the beginning to the end of rewarming (from 1,611 +/- 396 to 141 +/- 361 mg/min for Con and 1,555 +/- 230 to 207 +/- 261 mg/min for Pre-CE). In contrast, lipid oxidation rate remained constant and low (relatively to maximal rates at exercise) throughout rewarming, averaging 183 +/- 141 for Con and 207 +/- 118 mg lipids/min for Pre-CE. In addition, this pattern of fuel selection remained the same between treatments. We concluded that fuel selection is regulated entirely by changes in CHO oxidation rate. Further research should focus on establishing the exact regulatory processes involved in achieving this large upregulation of CHO utilization rate following hypothermia.  (+info)