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Acid-base regulation during heating and cooling in the lizard, Varanus exanthematicus.

Current concepts of acid-base balance in ectothermic animals require that arterial pH vary inversely with body temperature in order to maintain a constant OH-/H+ and constant net charge on proteins. The present study evaluates acid-base regulation in Varanus exanthematicus under various regimes of heating and cooling between 15 and 38 degrees C. Arterial blood was sampled during heating and cooling at various rates, using restrained and unrestrained animals with and without face masks. Arterial pH was found to have a small temperature dependence, i.e., pH = 7.66--0.005 (T). The slope (dpH/dT = -0.005), while significantly greater than zero (P less than 0.05), is much less than that required for a constant OH-/H+ or a constant imidazole alphastat (dpH/dT congruent to 0.018). The physiological mechanism that distinguishes this species from most other ectotherms is the presence of a ventilatory response to temperature-induced changes in CO2 production and O2 uptake, i.e., VE/VO2 is constant. This results in a constant O2 extraction and arterial saturation (approx. 90%), which is adaptive to the high aerobic requirements of this species.

Acid-Base Equilibrium↗

Effects of subanesthetic doses of inert gases on behavioral thermoregulation in mice.

Mice exposed to subanesthetic partial pressures of N2O (0.25 to 0.75 atm) or N2 (5.7 or 11.33 atm) and allowed to choose between a warm and a cool environment showed a marked preference for the cooler environment. This behavior was associated with the onset of hypothermia, with deep body temperature falling by up to about 3 degrees C, usually to a new, steady level. Both the length of time spent in the cooler environment and the degree of the hypothermia produced increased with the partial pressure of N2O or N2 used. The effects of N2O on behavioral thermoregulation and body temperature were reversible. There was a correlation between anesthetic potency and the ability of both gases to alter thermoregulation, suggesting that the effect of these agents on thermoregulation was caused by the same molecular interactions as those which underlie anesthesia. Since both gases elicited changes in behavioral thermoregulation promoting rather than opposing the onset of hypothermia, it is concluded that they may have acted to lower the level at which deep body temperature was being regulated.

Anesthetics↗

Radio frequency (13.56 MHz) energy enhances recovery from mild hypothermia.

The rate of warming after hypothermia depends on the method of rewarming. This study compared the effectiveness of radio frequency (RF) energy against hot (41 degrees C) water immersion (HW) and an insulated cocoon (IC) for rewarming hypothermic men. Six men fasted overnight and were rewarmed for 1 h after attaining a 0.5 degree C reduction in rectal temperature (Tre). Tre and esophageal (Tes) temperature were recorded every 5 min with nonmetallic thermal probes. The base-line value for Tre and Tes just before rewarming was subtracted from each 5 min Tre and Tes during rewarming to give delta Tre and delta Tes. The 12 delta Tes values were averaged for each individual and were compared using analysis of variance. The average delta Tes for RF (1.15 +/- 0.22 degrees C/h) was faster (P less than 0.001) than either IC (0.37 +/- 0.16 degrees C/h) or HW (0.18 +/- 0.09 degree C/h). The present study shows the superiority of RF energy for rewarming mildly hypothermic men.

Adult↗

Adequacy of food rations in soldiers during an arctic exercise measured by doubly labeled water.

To investigate the adequacy of food rations to supply energy needs in cold-temperature environments, caloric expenditure and intake and body composition changes were measured in a group of infantrymen during a 10-day field exercise in the Canadian Arctic. Energy expenditure was measured by the doubly labeled water method (n = 10), and caloric intake was measured by complete food intake records (n = 20). Body composition was determined by isotope dilution (n = 10) and bioelectrical impedence analysis (n = 20) on days 0 and 10. Baseline isotopic enrichment shifts due to geographical relocation were also monitored (n = 5). Mean body weight decreased 0.63 +/- 0.83 (SD) kg over the study period (P < 0.005), although fat-free and fat mass compartment changes were not significant. Baseline isotopic changes were -4.65 +/- 2.54 and -0.48 +/- 0.07 /1000/day for deuterium and 18O, respectively. Mean baseline corrected energy expenditure level was 4,317 +/- 927 kcal/day. Self-reported caloric intakes obtained from food records were 2,633 +/- 499 kcal/day (61.0% of expenditure). Rations packs contained 4,350 kcal/day. Results suggest that 1) food intake was significantly underreported and 2) the energy needs of most subjects were being met by rations and available supplements.

Arctic Regions↗

Inhaled furosemide attenuates hyperpnea-induced obstruction and intra-airway thermal gradients.

Inhaled furosemide attenuates exercise- and isocapnic hyperventilation-induced asthma; however, the mechanism for this phenomenon is unknown. Because the magnitude of the intra-airway thermal gradient that develops between the cooling of hyperpnea and the rewarming that occurs once hyperventilation ceases is directly related to the severity of thermally induced obstruction in humans, we wondered if furosemide blunted these temperature changes. To explore this issue, eight asthmatic subjects had tracheobronchial airstream temperature measures as they performed isocapnic hyperventilation with frigid air alone (HV) or with pretreatment with inhaled saline (S + HV) or 45 +/- 3 (SE) mg of furosemide (F + HV). HV and S + HV resulted in similar degrees of obstruction, whereas the mechanical decrements after F + HV were significantly less. In concert with this protective effect, F + HV resulted in less airstream cooling during hyperventilation and slower rewarming in the recovery period. Because the major source of heat to the airways is provided by its microcirculation, inhaled furosemide may be acting as a topical vasodilator serving to enhance heat availability and thus reducing the effective thermal burden of hyperpnea.

Administration, Inhalation↗

Effects of pulmonary air embolism on discharge of slowly adapting pulmonary stretch receptors.

Pulmonary air embolism (PAE) usually causes small-airway collapse. Local transpulmonary pressure (Ptr) is thought to be closely associated with the activity of slowly adapting pulmonary stretch receptors (SAPSRs). To test whether discharge of SAPSRs located distal to collapsed airways is closely related to the overall Ptr, we studied 65 SAPSRs in anesthetized paralyzed open-chest dogs that were ventilated at constant tidal volume and frequency. PAE increased both Ptr and total pulmonary resistance but decreased dynamic lung compliance. Three groups of SAPSRs were identified on the basis of their locations in intrapulmonary airways. Group I had 29 SAPSRs located in airways < 1 mm in diameter. Group II had 10 SAPSRs that were found in intrapulmonary airways between 1 and 2 mm in diameter. PAE decreased the activity of 31 of the 39 SAPSRs in these two groups. Their activity during PAE was not related to Ptr. The 26 SAPSRs in group III were in airways > 2 mm in diameter. PAE increased the peak firing rate of 18 of these receptors, and there was a close relationship between the discharge frequency of these SAPSRs and the Ptr during PAE. In groups I and II, the dissociation between Ptr and SAPSR activity during PAE may have been caused by peripheral airway collapse. Activity of central fibers was blocked at higher temperatures than activity of peripheral fibers. We suggest that the response of a SAPSR to PAE depends on the location of the receptor within the lungs, and we speculate that threshold and fiber type are also related to location.

Airway Resistance↗

Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats.

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60-100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.

Anesthesia↗

Efficacy of forced-air and inhalation rewarming by using a human model for severe hypothermia.

We recently developed a nonshivering human model for severe hypothermia by using meperidine to inhibit shivering in mildly hypothermic subjects. This thermal model was used to evaluate warming techniques. On three occasions, eight subjects were immersed for approximately 25 min in 9 degrees C water. Meperidine (1.5 mg/kg) was injected before the subjects exited the water. Subjects were then removed, insulated, and rewarmed in an ambient temperature of -20 degrees C with either 1) spontaneous rewarming (control), 2) inhalation rewarming with saturated air at approximately 43 degrees C, or 3) forced-air warming. Additional meperidine (to a maximum cumulative dose of 2.5 mg/kg) was given to maintain shivering inhibition. The core temperature afterdrop was 30-40% less during forced-air warming (0.9 degree C) than during control (1.4 degrees C) and inhalation rewarming (1.2 degrees C) (P < 0.05). Rewarming rate was 6- to 10-fold greater during forced-air warming (2.40 degrees C/h) than during control (0.41 degree C/h) and inhalation rewarming (0.23 degree C/h) (P < 0.05). In nonshivering hypothermic subjects, forced-air warming provided a rewarming advantage, but inhalation rewarming did not.

Adult↗

Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise.

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3 degrees C (CT), 20 degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher (P < 0.05) when HT was compared with NT, which in turn was higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher (P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase (P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.

Adult↗

Effect of body temperature during exercise on skeletal muscle cytochrome c oxidase content.

This study determined the role of body temperature during exercise on cytochrome-c oxidase (CytOx) activity, a marker of mitochondrial content, and mitochondrial heat shock protein 70 (mtHSP70), which is required for import of nuclear-coded preproteins. Male, 10-wk-old, Sprague-Dawley rats exercised identically for 9 wk in ambient temperatures of 23 degrees C (n = 10), 8 degrees C with wetted fur (n = 8), and 4 degrees C with wetted fur and fan (n = 7). These conditions maintained exercising core temperature (T(c)) at 40.4, 39.2, or 38.0 degrees C (resting temperature), respectively. During weeks 3-9, exercisers ran 5 days/wk up a 6% grade at 20 m/min for 60 min. Animals were housed at 23 degrees C. Gastrocnemius CytOx activity in T(c)=38.0 degrees C (83.5 +/- 5.5 microatoms O x min(-1) x g wet wt(-1)) was greater than all other groups (P < 0.05), exceeding sedentary (n = 7) by 73.2%. T(c) of 40.4 and 39.2 degrees C also were higher than sedentary by 22.4 and 37.4%, respectively (P < 0.05). Quantification of CytOx content verified that the increased activity was due to an increase in protein content. In extensor digitorum longus, a nonactive muscle, CytOx was not elevated in T(c) = 38.0 degrees C. mtHSP70 was significantly elevated in gastrocnemius of T(c) = 38.0 degrees C compared with sedentary (P < 0.05) but was not elevated in extensor digitorum longus (P > 0.05). The data indicate that decreasing exercise T(c) may enhance mitochondrial biogenesis and that mtHSP70 expression is not dependent on temperature.

Animals↗

Effect of water temperature on cooling efficiency during hyperthermia in humans.

We evaluated the cooling rate of hyperthermic subjects, as measured by rectal temperature (T(re)), during immersion in a range of water temperatures. On 4 separate days, seven subjects (4 men, 3 women) exercised at 65% maximal oxygen consumption at an ambient temperature of 39 degrees C until T(re) increased to 40 degrees C (45.4 +/- 4.1 min). After exercise, the subjects were immersed in a circulated water bath controlled at 2, 8, 14, or 20 degrees C until T(re) returned to 37.5 degrees C. No difference in cooling rate was observed between the immersions at 8, 14, and 20 degrees C despite the differences in the skin surface-to-water temperature gradient, possibly because of the presence of shivering at 8 and 14 degrees C. Compared with the other conditions, however, the rate of cooling (0.35 +/- 0.14 degrees C/min) was significantly greater during the 2 degrees C water immersion, in which shivering was seldom observed. This rate was almost twice as much as the other conditions (P < 0.05). Our results suggest that 2 degrees C water is the most effective immersion treatment for exercise-induced hyperthermia.

Adult↗

Altered frequency responses of sympathetic nerve discharge bursts after IL-1beta and mild hypothermia.

Although interleukin-1beta (IL-1beta) administration produces nonuniform changes in the level of sympathetic nerve discharge (SND), the effect of IL-1beta on the frequency-domain relationships between discharges in different sympathetic nerves is not known. Autospectral and coherence analyses were used to determine the effect of IL-1beta and mild hypothermia (60 min after IL-1beta, colonic temperature from 38 degrees C to 36 degrees C) on the relationships between renal-interscapular brown adipose tissue (IBAT) and splenic-lumbar sympathetic nerve discharges in chloralose-anesthetized rats. The following observations were made. 1) IL-1beta did not alter renal-IBAT coherence values in the 0- to 2-Hz frequency band or at the cardiac frequency (CF). 2) Peak coherence values relating splenic-lumbar discharges at the CF were significantly increased after IL-1beta and during hypothermia. 3) Hypothermia after IL-1beta significantly reduced the coupling (0-2 Hz and CF) between renal-IBAT but not splenic-lumbar SND bursts. 4) Combining IL-1beta and mild hypothermia had a greater effect on renal-IBAT SND coherence values than did mild hypothermia alone. These data demonstrate functional plasticity in sympathetic neural circuits and suggest complex relationships between immune products and SND regulation.

Acute-Phase Reaction↗

Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades.

Dorsolateral prefrontal and posterior parietal cortex share reciprocal projections. They also share nearly identical patterns of neuronal activation during performance of memory-guided saccades. To test the hypothesis that the reciprocal projections between parietal and prefrontal neurons may entrain their parallel activation, the present experiments have combined cortical cooling in one cortical area with single-unit recording in the other to more precisely determine the physiological interactions between the two during working memory performance. The activity of 105 cortical neurons during the performance of an oculomotor delayed response (ODR) task (43 parietal neurons during prefrontal cooling, 62 prefrontal neurons during parietal cooling) was compared across two blocks of trials collected while the distant cortical area either was maintained at normal body temperature or cooled. The mean firing rates of 71% of the prefrontal neurons during ODR performance changed significantly when parietal cortex was cooled. Prefrontal neurons the activity of which was modulated during the cue, delay, or saccade periods of the task were equally vulnerable to parietal inactivation. Further, both lower and higher firing rates relative to the precool period were seen with comparable frequency. Similar results were obtained from the converse experiment, in which the mean firing rates of 76% of the parietal neurons were significantly different while prefrontal cortex was cooled, specifically in those task epochs when the activity of each neuron was modulated during ODR performance. These effects again were seen equally in all epochs of the ODR task in the form of augmented or suppressed activity. Significant effects on the latency of neuronal activation during cue and saccade periods of the task were absent irrespective of the area cooled. Cooling was associated in some cases with a shift in the best direction of Gaussian tuning functions fit to neuronal activity, and these shifts were on average larger during parietal than prefrontal cooling. In view of the parallel between the similarity in activity patterns previously reported and the largely symmetrical cooling effects presently obtained, the data suggest that prefrontal and parietal neurons achieve matched activation during ODR performance through a symmetrical exchange of neuronal signals between them; in both cortical areas, neurons activated during the cue, delay, and also saccade epochs of the ODR task participate in reciprocal neurotransmission; and the output of each cortical area produces a mixture of excitatory and inhibitory drives within its target.

Animals↗

Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature.

Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as -2.9 degrees C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0 degrees C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.

Adaptation, Physiological↗

[Fluorescence diagnosis with 5-ALA thermogel of cervical intraepithelial neoplasia].

OBJECTIVE: To study the pharmacokinetics and selectivity of 5-aminolevulinic acid (5-ALA) from 5-ALA thermolabile gel formulation in cervical intraepithelial neoplasia (CIN). The novel thermogel Pluronic F127 is liquid at cold temperatures and turns into a gel-like consistency at body temperature, thereby improving adhesion of 5-ALA to the cervix uteri. METHODS: 27 female patients with CIN 1-3 were included in this study. Thirty minutes to 12 h before conisation, 10 mL of thermo-gel containing either 4, 10, or 20% of 5-ALA were topically applied to the cervix. Biopsies were taken from the lesions as well as normal surrounding epithelial tissue for histological examination, fluorescence microscopy and spectrometry. RESULTS: The thermogel Pluronic F127 was easy to handle and proved reliable as vehicle carrier. 5-ALA induced porphyrin fluorescence was maximal after application of 10% 5-ALA thermogel. We observed the higher porphyrin fluorescence intensity within the CIN lesions (1,116 +/- 241 AU), as compared to normal adjacent epithelium (704 +/- 166 AU). This difference was statistically significant (p < 0.05). Four to six hours after application, porphyrin fluorescence in dysplastic epithelium reached maximal intensity, and tumor selectivity was the highest in CIN 3 achieving a tumor-to-normal ratio of 3.5. Compared to other studies employing 5-ALA, the thermogel preparation of 5-ALA leads to twofold increase in the porphyrin selectivity. CONCLUSIONS: The thermogel Pluronic F127 seems to improve the local cervical drug application. Based on these results, we recommend the application of a 10% 5-ALA thermogel formulation 4-6 h prior to photodynamic therapy in CIN.

Adult↗

Liquid incubator with perfluorochemicals for extremely premature infants.

OBJECTIVES: Maintenance of appropriate body temperature, humidification and prevention of skin injury are very important in the management of extremely premature infants with immature skin. We have developed a new closed liquid incubator, utilising the characteristics of perfluorochemical (PFC) liquids, i.e., high specific gravity and chemical and biological inertness. The potential of this incubator to control body temperature was evaluated in rats. METHODS: PFC liquid (FC43; 3M Company, Tokyo, Japan) within the incubator was heated or cooled and the rectal temperature of each rat and the PFC temperature were monitored. RESULTS: The rectal temperature of rats floating on the PFC liquid surface changed almost in parallel to the temperature of PFC within the incubator, indicating that this technique can be used to warm or cool adults rats in a stable manner. The relative humidity of air within the incubator was maintained constant at 100%. CONCLUSIONS: The liquid incubator used in the present study maintained an environment with a relative humidity of 100% and allowed stable maintenance of temperature in adult rats. We also demonstrated that heating and cooling the PFC liquid allowed control of body temperature. Although further studies are required, this new incubator may be useful for the clinical management of extremely premature infants.

Animals↗

Role of receptor cycling in the regulation of angiotensin II surface receptor number and angiotensin II uptake in rat vascular smooth muscle cells.

In vivo data on the factors controlling angiotensin II (AII) cell surface binding are conflicting. We studied the specific effects of AII on AII binding in rat mesenteric artery vascular smooth muscle cells in culture. Incubation with unlabeled AII at 21 degrees C resulted in time- and concentration-dependent decreases in AII surface binding at 4 degrees C, with a 30% reduction after exposure to 300 nM AII for 15 min. Reductions in cell surface binding were due to decrements in receptor number rather than changes in binding affinity. Loss of surface receptors was mediated by receptor internalization as maneuvers that blocked ligand internalization (cold temperature and phenylarsine oxide [PAO]) attenuated AII-induced loss of surface receptors. After removal of AII, recovery of surface binding was rapid (t1/2 = 15 min) and was mediated by reinsertion of a preexisting pool of receptors into the surface membrane rather than by new receptor synthesis. To determine the role of receptor cycling on AII-induced surface receptor loss, cells were incubated with the endosomal inhibitor chloroquine during exposure to AII at 21 degrees C. Incubation with AII plus chloroquine resulted in a 70% greater loss of surface binding than after incubation with AII alone. To determine the role of receptor cycling on uptake of ligand, cells were incubated with PAO or endosomal inhibitors during exposure to AII at 4 and 21 degrees C. Compared with buffer these agents did not alter AII uptake at 4 degrees C, but decreased uptake by 12-50% at 21 degrees C. These results indicate that after binding AII receptors cycle and that receptor cycling attenuates AII-induced losses of surface receptors and enhances ligand uptake by providing a continuous source of receptors to the cell surface.

Angiotensin II↗