Normothermic Levels Research Articles

Functional role of metabolic suppression in avian thermoregulation in the heat

Hypometabolism arising from active metabolic suppression occurs in several contexts among endotherms, particularly during heterothermic states such as torpor. However, observed Q10 ≈ 1 for avian resting metabolic rate within the thermoneutral zone, values far below the Q10 = 2–3 expected on the basis of Arrhenius effects, suggests hypometabolism also plays a role in birds’ thermoregulation at environmental temperatures approaching or exceeding normothermic body temperature (Tb). We evaluated the occurrence of hypometabolism during heat exposure among birds by re-analysing literature data to quantify changes in Tb and resting metabolic rate (RMR) near the upper boundary of the thermoneutral zone, at air temperatures (Tair) between the inflection above which Tb increases above normothermic levels (Tb.inf) and the upper critical limit of thermoneutrality (Tuc). Among the ∼55 % of species in which Tuc – Tb.inf > 0, Q10 < 2–3 occurred in nine of 10 orders for which suitable data exist, indicating that hypometabolism during heat exposure is widespread across the avian phylogeny. Values of Q10 < 2–3 were not restricted to small body mass, as previously proposed. Our findings support the idea that metabolic suppression reduces avian metabolic heat production and hence evaporative cooling requirements during heat exposure, with reductions of 20–30 % in RMR in some species. Moreover, these findings add to evidence that hypometabolism is an important component of heat tolerance among endotherms such as birds and tropical arboreal mammals.

Heat tolerance and evaporative cooling capacity in an arid-zone elephant shrew

Endotherms vary widely in their capacity to defend sublethal body temperature (Tb) during acute heat exposure. Interspecific variation in the upper thermal limits of small mammals remains poorly studied, particularly in taxa other than bats. We hypothesised that rupicolous elephant shrews (Macroscelidae), on account of their occupancy of above-ground rock crevices in hot habitats and rapid cursorial locomotion, have evolved pronounced heat tolerance capacities. To test this hypothesis, we quantified relationships between Tb, resting metabolic rate (RMR) and evaporative water loss (EWL) in western rock elephant shrews (Elephantulus rupestris) exposed to air temperature (Tair) approaching or exceeding Tb under conditions of low humidity representative of the study population’s arid, winter-rainfall habitat in western South Africa. Our data revealed a pronounced capacity to tolerate Tair > Tb, with E. rupestris tolerating Tair up to 48.0 ± 0.1 °C while defending Tb > 7 °C below Tair (maximum Tb = 41.64 ± 0.16 °C). Three behavioural pathways were employed to dissipate heat: open mouth panting, flattening their body posture, and nose-licking. At the highest experimental Tair values achieved, EWL increased 15.05-fold relative to normothermic levels and heat was dissipated evaporatively at rates equivalent to 174%—240% of metabolic heat production. The heat tolerance limit of Tair = 48 °C in E. rupestris is one of the highest yet recorded in a non-volant small mammal, and our data support the notion that elephant shrews possess a pronounced capacity to avoid lethal hyperthermia during acute heat exposure.

COOLING BY DOUSING WITH COLD WATER DOES NOT ALTER THE PATHOPHYSIOLOGICAL BIOCHEMICAL CHANGES INDUCED BY CAPTURE IN BLESBOK (DAMALISCUS PYGARGUS PHILLIPSI).

Wild animals are commonly captured for conservation, research, and wildlife management purposes. However, capture is associated with a high risk of morbidity or mortality. Capture-induced hyperthermia is a commonly encountered complication believed to contribute significantly to morbidity and mortality. Active cooling of hyperthermic animals by dousing with water is believed to treat capture-induced pathophysiological effects, but remains untested. This study aimed to determine the pathophysiological effects of capture, and whether cooling by dousing with cold water effectively reduces these effects in blesbok (Damaliscus pygargus phillipsi). Thirty-eight blesbok were randomly allocated into three groups: a control group that was not chased (Ct, n=12), chased not cooled (CNC, n=14), and chased plus cooled group (C+C, n=12). The CNC and C+C groups were chased for 15 min prior to chemical immobilization on day 0. Animals in the C+C group were cooled with 10 L of cold water (4 C) for 10 min during immobilization. All animals were immobilized on days 0, 3, 16, and 30. During each immobilization, rectal and muscle temperatures were recorded, and arterial and venous blood samples collected. Blesbok in the CNC and C+C groups presented with capture-induced pathophysiological changes characterized by hyperthermia, hyperlactatemia, increased markers of liver, skeletal, and cardiac muscle damage, hypoxemia, and hypocapnia. Cooling effectively returned body temperatures to normothermic levels, but neither the magnitude nor the duration of the pathophysiological changes differed between the CNC and C+C groups. Therefore, at least in blesbok, capture-induced hyperthermia appears not to be the primary cause of the pathophysiological changes, but is more likely a clinical sign of the hypermetabolism resulting from capture-induced physical and psychological stress. Although cooling is still recommended to prevent the compounding cytotoxic effects of persistent hyperthermia, it is unlikely to prevent stress- and hypoxia-induced damage caused by the capture procedure.

Heat shock factor 1 induces a short burst of transcription of the clock gene Per2 during interbout arousal in mammalian hibernation

During winter hibernation, a diverse range of small mammals can enter prolonged torpor. They spend the nonhibernation season as a homeotherm but the hibernation season as a heterotherm. In the hibernation season, chipmunks (Tamias asiaticus) cycle regularly between 5 and 6days-long deep torpor with a body temperature (Tb) of 5 to 7 °C and interbout arousal of ∼20h, during which, their Tb returns to the normothermic level. Here, we investigated Per2 expression in the liver to elucidate the regulation of the peripheral circadian clock in a mammalian hibernator. In the nonhibernation season, as in mice, heat shock factor 1, activated by elevated Tb during the wake period, activated Per2 transcription in the liver, which contributed to synchronizing the peripheral circadian clock to the Tb rhythm. In the hibernation season, we determined that the Per2 mRNA was at low levels during deep torpor, but Per2 transcription was transiently activated by heat shock factor 1, which was activated by elevated Tb during interbout arousal. Nevertheless, we found that the mRNA from the core clock gene Bmal1 exhibited arrhythmic expression during interbout arousal. Since circadian rhythmicity is dependent on negative feedback loops involving the clock genes, these results suggest that the peripheral circadian clock in the liver is nonfunctional in the hibernation season.

Changes in Body Surface Temperature Play an Underappreciated Role in the Avian Immune Response.

AbstractFever and hypothermia are well-characterized components of systemic inflammation. However, our knowledge of the mechanisms underlying such changes in body temperature is largely limited to rodent models and other mammalian species. In mammals, high dosages of an inflammatory agent (e.g., lipopolysaccharide [LPS]) typically leads to hypothermia (decrease in body temperature below normothermic levels), which is largely driven by a reduction in thermogenesis and not changes in peripheral vasomotion (i.e., changes in blood vessel tone). In birds, however, hypothermia occurs frequently, even at lower dosages, but the thermoeffector mechanisms associated with the response remain unknown. We immune challenged zebra finches (Taeniopygia guttata) with LPS, monitored changes in subcutaneous temperature and energy balance (i.e., body mass, food intake), and assessed surface temperatures of and heat loss across the eye region, bill, and legs. We hypothesized that if birds employ thermoregulatory mechanisms similar to those of similarly sized mammals, LPS-injected individuals would reduce subcutaneous body temperature and maintain constant surface temperatures compared with saline-injected individuals. Instead, LPS-injected individuals showed a slight elevation in body temperature, and this response coincided with a reduction in peripheral heat loss, particularly across the legs, as opposed to changes in energy balance. However, we note that our interpretations should be taken with caution owing to small sample sizes within each treatment. We suggest that peripheral vasomotion, allowing for heat retention, is an underappreciated component of the sickness-induced thermoregulatory response of small birds.

Experimental evidence that hyperthermia limits offspring provisioning in a temperate-breeding bird.

In many vertebrates, parental care can require long bouts of daily exercise that can span several weeks. Exercise, especially in the heat, raises body temperature, and can lead to hyperthermia. Typical strategies for regulating body temperature during endurance exercise include modifying performance to avoid hyperthermia (anticipatory regulation) and allowing body temperature to rise above normothermic levels for brief periods of time (facultative hyperthermia). Facultative hyperthermia is commonly employed by desert birds to economize on water, but this strategy may also be important for chick-rearing birds to avoid reducing offspring provisioning when thermoregulatory demands are high. In this study, we tested how chick-rearing birds balance their own body temperature against the need to provision dependent offspring. We experimentally increased the heat dissipation capacity of breeding female tree swallows (Tachycineta bicolor) by trimming their ventral feathers and remotely monitored provisioning rates, body temperature and the probability of hyperthermia. Birds with an experimentally increased capacity to dissipate heat (i.e. trimmed treatment) maintained higher feeding rates than controls at high ambient temperatures (greater than or equal to 25°C), while maintaining lower body temperatures. However, at the highest temperatures (greater than or equal to 25°C), trimmed individuals became hyperthermic. These results provide evidence that chick-rearing tree swallows use both anticipatory regulation and facultative hyperthermia during endurance performance. With rising global temperatures, individuals may need to increase their frequency of facultative hyperthermia to maintain nestling provisioning, and thereby maximize reproductive success.

Winter thermoregulation in free-ranging pygmy falcons in the Kalahari Desert

Among birds, pronounced heterothermy tends to be used by small species belonging to phylogenetically older taxa and inhabiting environments with unpredictable and/or seasonally scarce food resources. Previous evidence suggests that a small arid-zone raptor, the pygmy falcon (Polihierax semitorquatus), enters torpor and decreases its body temperature (Tb) to below 31 °C on winter nights in the Kalahari Desert, where sub-zero night-time temperatures occur regularly. To confirm that this species has the capacity for heterothermy and to characterise its thermoregulatory patterns under natural conditions, we implanted temperature-sensitive radio transmitters into free-ranging falcons. Based on data from seven individuals, we found no evidence for the substantial reductions in Tb previously reported. The mean minimum rest-phase Tb during the study period was 37.89 ± 0.67 °C, we observed no instances of Tb < 36 °C, and air temperature did not significantly influence patterns of thermoregulation. Our results highlight intraspecific variability in heterothermy among birds and reveal that, contrary to previous suggestions, even in mid-winter pygmy falcons may not reduce Tb below normothermic levels.

Turning Down the Heat: Role of Sarcolpin in Thermoregulation of Hibernating Arctic Ground Squirrels

Hibernation in mammals is a whole‐body phenotype that involves profound reductions in metabolism and core body temperature resulting in a state of torpor. Some mammalian hibernators, such as ground squirrels, have the ability to reverse this state of hypometabolism by rewarming periodically (~every 1–4 weeks) to normothermic levels. The predominant sources of thermogenesis during these arousal periods have been shown to be brown adipose tissue (BAT) and skeletal muscle shivering. Recently, skeletal muscle non‐shivering thermogenesis has been speculated to be a significant source of heat production, which may occur via sarcolipin (SLN) uncoupling of sarcoendoplasmic reticulum (SR) calcium ATPase (SERCA)‐mediated calcium pumping. During torpor, the thermogenic contribution of BAT and skeletal muscle need to be reduced in order for hibernating mammals to maintain hypometabolic conditions. We hypothesized that skeletal muscle non‐shivering thermogenesis is a significant source of heat production and, in hibernating mammals, must be reduced during torpor. Skeletal muscle samples were taken from 2 species of ground squirrels (13‐lined and Arctic), in and out of torpor conditions, to assess fluctuations in protein expression. Preliminary results show that SLN expression is decreased during periods of torpor and significantly increase after terminal arousal from hibernation in the spring in both ground squirrel species. Furthermore, SERCA expression significantly increased during torpor in Arctic ground squirrels, which fell to normothermic levels post arousal, suggesting an enhancement of calcium handling during torpor. Next, Arctic ground squirrels were implanted with peristaltic pumps subcutaneously which delivered inhibitors of BAT‐uncoupling (SR59230A) or skeletal muscle‐uncoupling (dantrolene) during hibernation to quantify the effect of reducing specific thermogenic mechanisms directly on rewarming and metabolic rate during interbout arousals. To measure metabolic rate changes in AGS, VO2 was monitored during rewarming using respirometry. Results show that suppressing skeletal muscle uncoupling; using dantrolene (RyR inhibitor that decreases cytosolic calcium) caused a dose dependent reduction in metabolic rate during AGS rewarming. Inhibition of BAT thermogenesis resulted in faster rates of metabolism increase during IBAs. These data suggest that skeletal muscle nonshivering thermogenesis could be a significant regulator of core body temperature and basal metabolic rate, which need to be suppressed during hibernation to maintain torpor.Support or Funding InformationThirteen lined ground squirrel data funded by NIH Grant 1RC2HL101625‐01, U.S. Army Medical Research and Materiel Command contract W81XWH‐11‐0409, and the University of Minnesota McKnight Presidential Endowment. Arctic Ground Squirrel data supported by a UAF INBRE IDeA pilot award from NIH NIGMS grant number P20GM103395.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The functional significance of facultative hyperthermia varies with body size and phylogeny in birds

Abstract Facultative hyperthermia, the elevation of body temperature above normothermic levels, during heat exposure, importantly affects the water economy and heat balance of terrestrial endotherms. We currently lack a mechanistic understanding of the benefits hyperthermia provides for avian taxa. Facultative hyperthermia has been proposed to minimize rates of water loss via three distinct mechanisms: M1) by maintaining body temperature (Tb) above environmental temperatures (Te), heat can be lost non‐evaporatively, saving water; M2) by minimizing the thermal gradient when Te &gt; Tb, environmental heat gain and evaporative water loss rates are reduced; and M3) by storing heat via increases in Tb which reduces evaporative heat loss demands and conserves water. Although individuals may benefit from all three mechanisms during heat exposure, the relative importance of each mechanism has not been quantified among species that differ in their body size, heat tolerance and mechanisms of evaporative heat dissipation. We measured resting metabolism, evaporative water loss and real‐time Tb from 33 species of birds representing nine orders ranging in mass from 8 to 300 g and estimated the water savings associated with each proposed mechanism. We show that facultative hyperthermia varies in its benefits among species. Small songbirds with comparatively low evaporative cooling capacities benefit most from (M1), and hyperthermia maintains a thermal gradient that allows non‐evaporative heat losses. Other species benefited most from (M2) minimizing evaporative losses via a reduced thermal gradient for heat gain at high Te. We found that (M3), heat storage, only improved the water economy of the sandgrouse, providing little benefit to other species. We propose that differences in the frequency and magnitude of hyperthermia will drive taxon‐specific differences in temperature sensitivity of tissues and enzymes and that the evolution of thermoregulatory mechanisms of evaporative heat dissipation may contribute to differences in basal metabolic rate among avian orders. Understanding the mechanistic basis of heat tolerance is essential to advance our understanding of the ecology of birds living in hot environments that are warming rapidly, where extreme heat events are already re‐structuring avian communities. A plain language summary is available for this article.

Precise Control of Target Temperature Using N6-Cyclohexyladenosine and Real-Time Control of Surface Temperature.

Targeted temperature management is standard of care for cardiac arrest and is in clinical trials for stroke. N6-cyclohexyladenosine (CHA), an A1 adenosine receptor (A1AR) agonist, inhibits thermogenesis and induces onset of hibernation in hibernating species. Despite promising thermolytic efficacy of CHA, prior work has failed to achieve and maintain a prescribed target core body temperature (Tb) between 32°C and 34°C for 24 hours. We instrumented Sprague-Dawley rats (n = 19) with indwelling arterial and venous cannulae and a transmitter for monitoring Tb and ECG, then administered CHA via continuous IV infusion or intraperitoneal (IP) injection. In the first experiment (n = 11), we modulated ambient temperature and increased the dose of CHA in an attempt to manage Tb. In the second experiment (n = 8), we administered CHA (0.25 mg/[kg·h]) via continuous IV infusion and modulated cage surface temperature to control Tb. We rewarmed animals by increasing surface temperature at 1°C h-1 and discontinued CHA after Tb reached 36.5°C. Tb, brain temperature (Tbrain), heart rate, blood gas, and electrolytes were also monitored. Results show that titrating dose to adjust for individual variation in response to CHA led to tolerance and failed to manage a prescribed Tb. Starting with a dose (0.25 mg/[kg·h]) and modulating surface temperature to prevent overcooling proved to be an effective means to achieve and maintain Tb between 32°C and 34°C for 24 hours. Increasing surface temperature to 37°C during CHA administration brought Tb back to normothermic levels. All animals treated in this way rewarmed without incident. During the initiation of cooling, we observed bradycardia within 30 minutes of the start of IV infusion, transient hyperglycemia, and a mild hypercapnia; the latter normalized via metabolic compensation. In conclusion, we describe an intravenous delivery protocol for CHA at 0.25 mg/(kg·h) that, when coupled with conductive cooling, achieves and maintains a prescribed and consistent target Tb between 32°C and 34°C for 24 hours.

Diurnal body temperature patterns in free‐ranging populations of two southern African arid‐zone nightjars

Endotherms allocate large amounts of energy and water to the regulation of a precise body temperature (Tb), but can potentially reduce thermoregulatory costs by allowing Tb to deviate from normothermic levels. Many data on heterothermy at low air temperatures (Ta) exist for caprimulgids, whereas data on thermoregulation at high Ta are largely absent, despite members of this taxon frequently roosting and nesting in sites exposed to high operative temperatures. We investigated thermoregulation in free‐ranging rufous‐cheeked nightjars Caprimulgus rufigena and freckled nightjars Caprimulgus tristigma in the southern African arid zone. Individuals of both species showed labile Tb fluctuating around a single modal Tb (Tb‐mod). Average Tb‐mod was 39.7°C for rufous‐cheeked nightjars and 39.0°C for freckled nightjars. In both species, diurnal Tb increased with increasing Ta. At Ta ≥ 38°C, rufous‐cheeked nightjar mean Tb increased to 42°C, equivalent to 2.3°C above Tb‐mod. Under similar conditions, freckled nightjar Tb was on average only 1.1°C above Tb‐mod, with a mean Tb of 40.0°C. Freckled nightjars are one of the most heterothermic caprimulgids investigated to date, but our data suggest that during hot conditions this species maintains Tb within a narrow range above Tb‐mod, possibly reflecting an evolutionary tradeoff between decreased thermal sensitivity to lower Tb but increased sensitivity to high Tb. These findings reveal how general thermoregulatory patterns at similar Ta can vary even among closely related species.

Can hibernators sense and evade fires? Olfactory acuity and locomotor performance during deep torpor.

Increased habitat fragmentation, global warming and other human activities have caused a rise in the frequency of wildfires worldwide. To reduce the risks of uncontrollable fires, prescribed burns are generally conducted during the colder months of the year, a time when in many mammals torpor is expressed regularly. Torpor is crucial for energy conservation, but the low body temperatures (T b) are associated with a decreased responsiveness and torpid animals might therefore face an increased mortality risk during fires. We tested whether hibernators in deep torpor (a) can respond to the smell of smoke and (b) can climb to avoid fires at T bs below normothermic levels. Our data show that torpid eastern pygmy-possums (Cercartetus nanus) are able to detect smoke and also can climb. All males aroused from torpor when the smoke stimulus was presented at an ambient temperature (T a) of 15°C (T b ∼18°C), whereas females only raised their heads. The responses were less pronounced at T a 10°C. The first coordinated movement of possums along a branch was observed at a mean T b of 15.6°C, and animals were even able to climb their prehensile tail when they reached a mean T b of 24.4°C. Our study shows that hibernators can sense smoke and move at low T b. However, our data also illustrate that at T b ≤13°C, C. nanus show decreased responsiveness and locomotor performance and highlight that prescribed burns during winter should be avoided on very cold days to allow torpid animals enough time to respond.

Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia does not contribute to hyperthermia-induced hyperventilation.

What is the central question of this study? Does baroreceptor unloading during passive hyperthermia contribute to increases in ventilation and decreases in end-tidal carbon dioxide during that exposure? What is the main finding and its importance? Hyperthermic hyperventilation is not mitigated by expanding central blood volume and reloading the cardiopulmonary baroreceptors via rapid saline infusion or by reloading the arterial baroreceptors via phenylephrine administration. The absence of a reduction in ventilation upon reloading the baroreceptors to pre-hyperthermic levels indicates that cardiopulmonary and arterial baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (P ET ,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ∼1.8°C) to cause a sustained increase in ventilation and reduction in P ET ,CO2. Upon attaining hyperthermic hyperventilation, in protocol1 (n=10; three females) a bolus (19±2mlkg(-1) ) of warm (∼38°C) isotonic saline was rapidly (5-10min) infused intravenously to restore reductions in central venous pressure, whereas in protocol2 (n=11; five females) phenylephrine was infused intravenously (60-120μgmin(-1) ) to return mean arterial pressure to normothermic levels. In protocol1, hyperthermia increased ventilation (by 2.2±1.7lmin(-1) , P<0.01), while reducing P ET ,CO2 (by 4±3mmHg, P = 0.04) and central venous pressure (by 5±1mmHg, P <0.01). Saline infusion increased central venous pressure by 5±1 mmHg (P<0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P>0.05). In protocol2, hyperthermia increased ventilation (by 5.0±2.7lmin(-1) , P <0.01) and reduced P ET ,CO2 (by 5±2 mmHg, P<0.01) and mean arterial pressure (by 9±7mmHg, P <0.01). Phenylephrine infusion increased mean arterial pressure by 12±3mmHg (P<0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P>0.05). The absence of a reduction in ventilation upon reloading the cardiopulmonary and arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans.

Effects of therapeutic hypothermia and kinetics of serum protein S100B after cardiopulmonary resuscitation

Introduction. Post-resuscitation care is regulated by international guidelines. A milestone of these is the application of therapeutic hypothermia (TH). The aims of our study were: to determine the 30-day-mortality for our patients, to monitor the efficacy and effects of TH, and to investigate serum protein S100B – as an early prognostic marker.Materials and Methods. In our study, 57 patients, treated after cardiopulmonary resuscitation (CPR) on a multidisciplinary intensive care unit, were included. Patients were divided into groups who received and who didn’t receive TH. 30-day-mortality was determined as an end-point. Effects of TH were monitored using statistical analysis according to clinical parameters and laboratory tests. Serum protein S100B levels were measured with ELISA technique on 20 randomised patients atadmission and the 1st, 3rd and 5th day after CPR. Results. Total 30-day-mortality was 74%. TH did not reduced the 30-day-mortality (73% vs. 74%, p>0.05). We found a significant correlation between TH and serum lactate concentration after admission (0h,p=0.006) and at 12 (p=0.045) and 36 (p=0.049) hours after CPR. On the3rd (p=0.005) and 4th (p=0.043) day after CPR, as a result of TH, platelet count was significantly higher compared to normothermic samples. There was no significant difference in protein S100B levels between the normothermic and TH group and protein S100B levels did not correlate with 30-day-mortality.Conclusion. Despite recommendations of international guidelines, we cannot prove the beneficial effect of TH, or a correlation of protein S100B levels with a positive outcome.

Baroreceptor unloading does not limit forearm sweat rate during severe passive heat stress.

This study tested the hypothesis that sweat rate during passive heat stress is limited by baroreceptor unloading associated with heat stress. Two protocols were performed in which healthy subjects underwent passive heat stress that elicited an increase in intestinal temperature of ∼1.8°C. Upon attaining this level of hyperthermia, in protocol 1 (n = 10, 3 females) a bolus (19 ml/kg) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to elevate central venous pressure (CVP), while in protocol 2 (n = 11, 5 females) phenylephrine was infused intravenously (60-120 μg/min) to return mean arterial pressure (MAP) to normothermic levels. In protocol 1, heat stress reduced CVP from 3.9 ± 1.9 mmHg (normothermia) to -0.6 ± 1.4 mmHg (P < 0.001), while saline infusion returned CVP to normothermic levels (5.1 ± 1.7 mmHg; P > 0.999). Sweat rate was elevated by heat stress (1.21 ± 0.44 mg·cm(-2)·min(-1)) but remained unchanged during rapid saline infusion (1.26 ± 0.47 mg·cm(-2)·min(-1), P = 0.5), whereas cutaneous vascular conductance increased from 77 ± 10 to 101 ± 20% of local heating max (P = 0.029). In protocol 2, MAP was reduced with heat stress from 85 ± 7 mmHg to 76 ± 8 mmHg (P = 0.048). Although phenylephrine infusion returned MAP to normothermic levels (88 ± 7 mmHg; P > 0.999), sweat rate remained unchanged during phenylephrine infusion (1.39 ± 0.22 vs. 1.41 ± 0.24 mg·cm(-2)·min(-1); P > 0.999). These data indicate that both cardiopulmonary and arterial baroreceptor unloading do not limit increases in sweat rate during passive heat stress.

Emergence of cognitive deficits after mild traumatic brain injury due to hyperthermia

Mild elevations in core temperature can occur in individuals involved in strenuous activities that are risky for potentially sustaining a mild traumatic brain injury (mTBI) or concussion. Recently, we have discovered that mild elevations in brain temperature can significantly aggravate the histopathological consequences of mTBI. However, whether this exacerbation of brain pathology translates into behavioral deficits is unknown. Therefore, we investigated the behavioral consequences of elevating brain temperature to mildly hyperthermic levels prior to mTBI. Adult male Sprague Dawley rats underwent mild fluid-percussion brain injury or sham surgery while normothermic (37°C) or hyperthermic (39°C) and were allowed to recover for 7days. Animals were then assessed for cognition using the water maze and cue and contextual fear conditioning. We found that mTBI alone at normothermia had no effect on long-term cognitive measures whereas mTBI animals that were hyperthermic for 15min prior to and for 4h after brain injury were significantly impaired on long-term retention for both the water maze and fear conditioning. In contrast, hyperthermic mTBI animals cooled within 15min to normothermia demonstrated no significant long-term cognitive deficits. Mild TBI irrespective of temperature manipulations resulted in significant short-term working memory deficits. Cortical atrophy and contusions were detected in all mTBI treatment groups and contusion volume was significantly less in hyperthermic mTBI animals that were cooled as compared to hyperthermic mTBI animals that remained hyperthermic. These results indicate that brain temperature is an important variable for mTBI outcome and that mildly elevated temperatures at the time of injury result in persistent cognitive deficits. Importantly, cooling to normothermia after mTBI prevents the development of long-term cognitive deficits caused by hyperthermia. Reducing temperature to normothermic levels soon after mTBI represents a rational approach to potentially mitigate the long-term consequences of mTBI.

Maximal local thermal hyperemia in able‐bodied and spinal cord injured humans (677.10)

Paraplegic spinal cord injury alters local thermal hyperemic responses. We hypothesized that a similar effect would be observed in tetraplegia. 6 able‐bodied (AB), 5 paraplegic (PARA), and 5 tetraplegic (TETRA) age and gender matched subjects participated. Skin blood flow (SkBF) was monitored by laser‐Doppler flowmetry (LDF) from forearm and calf sites. Local skin temperature (Tloc) was controlled with combined LDF/local heating probe holders. Tloc was measured with thermocouples placed between the probe holders and the skin. Mean arterial pressure (MAP) was recorded by Finapres. After instrumentation, Tloc was increased slowly from normothermic levels to 42°C and maintained at that temperature for at least 25 minutes to cause maximal local vasodilation. Cutaneous vascular conductance was calculated as CVC=LDF/MAP and analyzed by ANOVA. Results: At Tloc=42°C, CVC measured from forearm skin was 47±7mV in AB, 49±8mV in PARA, and 42±8mV in TETRA. These responses did not statistically differ among groups. At Tloc=42°C, CVC measured from calf skin was 26±7mV in AB, 50±8mV in PARA, and 42±8mV in TETRA. These responses differed between AB and PARA (p=0.04) and tended to differ between AB and TETRA (p=0.15). Within groups, forearm responses tended to be greater than calf responses in AB (p=0.06), but not in PARA and TETRA groups. We conclude that spinal cord injury alters maximal SkBF levels in the calf, but not the forearm. In AB persons, maximal SkBF tends to be lower in the calf than the forearm (supported by NIH Grant R03NS083961).Grant Funding Source: Supported by NIH R03NS083961

Ocular blood flow decreases during passive heat stress in resting humans.

BackgroundHeat stress induces various physiological changes and so could influence ocular circulation. This study examined the effect of heat stress on ocular blood flow.FindingsOcular blood flow, end-tidal carbon dioxide (PETCO2) and blood pressure were measured for 12 healthy subjects wearing water-perfused tube-lined suits under two conditions of water circulation: (1) at 35°C (normothermia) for 30 min and (2) at 50°C for 90 min (passive heat stress). The blood-flow velocities in the superior temporal retinal arteriole (STRA), superior nasal retinal arteriole (SNRA), and the retinal and choroidal vessels (RCV) were measured using laser-speckle flowgraphy. Blood flow in the STRA and SNRA was calculated from the integral of a cross-sectional map of blood velocity. PETCO2 was clamped at the normothermia level by adding 5% CO2 to the inspired gas. Passive heat stress had no effect on the subjects’ blood pressures. The blood-flow velocity in the RCV was significantly lower after 30, 60 and 90 min of passive heat stress than the normothermic level, with a peak decrease of 18 ± 3% (mean ± SE) at 90 min. Blood flow in the STRA and SNRA decreased significantly after 90 min of passive heat stress conditions, with peak decreases of 14 ± 3% and 14 ± 4%, respectively.ConclusionThe findings of this study suggest that passive heat stress decreases ocular blood flow irrespective of the blood pressure or arterial partial pressure of CO2.

Hyperthermic hyperventilation is not mitigated by cardiopulmonary baroreceptor loading

This study tested the hypothesis that cardiopulmonary baroreceptor loading would reverse increases in ventilation and decreases in end‐tidal carbon dioxide (CO2) that accompany hyperthermia. Ten individuals (29±5 y; 76±12 kg) underwent passive heat stress via a water perfused suit while intestinal temperature (HQ Inc.), mean skin temperature, central venous pressure (central venous catheter, CVP, n=8), minute ventilation, tidal volume (Parvo‐Medics) and end‐tidal CO2 (capnograph, PETCO2) were monitored. After intestinal temperature was elevated 1.9 ±0.5°C, causing a sustained rise in ventilation (by 2.9 ±2.8 L/min), and reductions in PETCO2 (by 4 ±3 mm Hg) and CVP (by 4 ±1 mm Hg), 19 ±2 ml/kg of warmed saline was rapidly (over 5–10 min) infused intravenously to increase CVP and return cardiopulmonary baroreceptor loading towards normothermic levels. Saline infusion increased CVP by 5 ±1 mm Hg (P &lt;0.01) but did not change (P &gt;;0.05) ventilation, tidal volume or PETCO2. Intestinal and skin temperatures did not change (P &gt;;0.05) with saline infusion. The absence of a reduction in ventilation upon returning cardiopulmonary baroreceptor loading to pre‐heat stress levels indicates that hyperthermic hyperventilation is not caused by cardiopulmonary baroreceptor unloading coincident with the heat stress. Supported by NIH Grant HL061388

Waking to drink: rates of evaporative water loss determine arousal frequency in hibernating bats

Bats hibernate to cope with low ambient temperatures (T(a)) and low food availability during winter. However, hibernation is frequently interrupted by arousals, when bats increase body temperature (T(b)) and metabolic rate (MR) to normothermic levels. Arousals account for more than 85% of a bat's winter energy expenditure. This has been associated with variation in T(b), T(a) or both, leading to a single testable prediction, i.e. that torpor bout length (TBL) is negatively correlated with T(a) and T(b). T(a) and T(b) were both found to be correlated with TBL, but correlations alone cannot establish a causal link between arousal and T(b) or T(a). Because hydration state has also been implicated in arousals from hibernation, we hypothesized that water loss during hibernation creates the need in bats to arouse to drink. We measured TBL of bats (Pipistrellus kuhlii) at the same T(a) but under different conditions of humidity, and found an inverse relationship between TBL and total evaporative water loss, independent of metabolic rate, which directly supports the hypothesis that hydration state is a cue to arousal in bats.