Corticospinal and spinal excitability during peripheral or central cooling in humans.

Cold exposure can impair fine and gross motor control and threaten survival. Most motor task decrement is due to peripheral neuromuscular factors. Less is known about cooling on central neural factors. Corticospinal and spinal excitability were determined during cooling of the skin (Tsk) and core (Tco). Eight subjects (four female) were actively cooled in a liquid perfused suit for 90 min (2 °C inflow temperature), passively cooled for 7 min, and then rewarmed for 30 min (41 °C inflow temperature). Stimulation blocks included 10 transcranial magnetic stimulations [eliciting motor evoked potentials (MEPs) which indicate corticospinal excitability], 8 trans-mastoid electrical stimulations [eliciting cervicomedullary evoked potentials (CMEPs) which indicate spinal excitability] and 2 brachial plexus electrical stimulations [eliciting maximal compound motor action potentials (Mmax)]. These stimulations were delivered every 30 min. Cooling for 90 min reduced Tsk to 18.2 °C while Tco did not change. At the end of rewarming Tsk returned to baseline while Tco decreased by 0.8 °C (afterdrop) (P < 0.001). Metabolic heat production was higher than baseline at the end of passive cooling (P = 0.01), and 7 min into rewarming (P = 0.04). MEP/Mmax remained unchanged throughout. CMEP/Mmax increased by 38% at end cooling (although increased variability at this time rendered the increase insignificant, P = 0.23) and 58% at end warming when Tco was 0.8 °C below baseline (P = 0.02). Cooling increased spinal excitability but not corticospinal excitability. Cooling may decrease cortical and/or supraspinal excitability which is compensated for by increased spinal excitability. This compensation is key to providing a motor task and survival advantage.

Cumulative effects of pre-pandemic vulnerabilities and pandemic-related hardship on psychological distress among pregnant individuals.

OBJECTIVE: Our primary objective was to determine whether pre-existing vulnerabilities and resilience factors combined with objective hardship resulted in cumulative (i.e., additive) effects on psychological distress in pregnant individuals during the COVID-19 pandemic. A secondary objective was to determine whether any of the effects of pandemic-related hardship were compounded (i.e., multiplicative) by pre-existing vulnerabilities. METHOD: Data are from a prospective pregnancy cohort study, the Pregnancy During the COVID-19 Pandemic study (PdP). This cross-sectional report is based upon the initial survey collected at recruitment between April 5, 2020 and April 30, 2021. Logistic regressions were used to evaluate our objectives. RESULTS: Pandemic-related hardship substantially increased the odds of scoring above the clinical cut-off on measures of anxiety and depression symptoms. Pre-existing vulnerabilities had cumulative (i.e., additive) effects on the odds of scoring above the clinical cut-off on measures of anxiety and depression symptoms. There was no evidence of compounding (i.e., multiplicative) effects. Social support had a protective effect on anxiety and depression symptoms, but government financial aid did not. CONCLUSION: Pre-pandemic vulnerability and pandemic-related hardship had cumulative effects on psychological distress during the COVID-19 pandemic. Adequate and equitable responses to pandemics and disasters may require more intensive supports for those with multiple vulnerabilities.

Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.

Fear of COVID-19, mental health, and pregnancy outcomes in the pregnancy during the COVID-19 pandemic study: Fear of COVID-19 and pregnancy outcomes.

BACKGROUND: Sustained fear during pregnancy has the potential to increase psychological distress and obstetric risk. This study aimed to (1) identify factors and characteristics associated with fear of COVID-19, (2) investigate the relationship between fear of COVID-19 and maternal anxiety and depression, and (3) determine the relationship between fear of COVID-19 and pregnancy outcomes. METHODS: 9251 pregnant Canadians were recruited between April - December 2020. Participants self-reported (scale of 0-100) the degree of threat they perceived from the SARS-CoV-2 virus in relation to themselves and their unborn baby. RESULTS: Mean fear scores indicated moderate to elevated concern. In multivariable linear regression, fear of COVID-19 was associated with food insecurity, ethnicity, geographic location, history of anxiety prior to pregnancy, having a chronic health condition, pre-pregnancy BMI, parity, and stage of pregnancy at study enrollment. Higher COVID-19 fear was associated with increased odds of depression, adjusted odds ratio (aOR) = 1.75, p < 0.001, 95% CI 1.66-1.85, and anxiety, aOR=2.04, p < 0.001, 95% CI 1.94-2.15). Furthermore, fear of COVID-19 was associated with a 192-gram reduction in infant birthweight, and a 6.1-day reduction in gestational age at birth. LIMITATIONS: The sample has higher education compared to the Canadian population and cannot test causal effects. CONCLUSION: This study suggests that sociodemographic, health, and obstetric factors may contribute to increased fear of COVID-19 and associated adverse psychological and pregnancy outcomes.

Beam power scale-up in micro-electromechanical systems based multi-beam ion accelerators.

We report on the development of multi-beam radio frequency (RF) linear ion accelerators that are formed from stacks of low cost wafers and describe the status of beam power scale-up using an array of 112 beams. The total argon ion current extracted from the 112-beamlet extraction column was 0.5 mA. The measured energy gain in each RF gap reached as high as 7.25 keV. We present a path toward using this technology to achieve ion currents >1 mA and ion energies >100 keV for applications in material processing.

Effect of a 20-day ski trek on fuel selection during prolonged exercise at low workload with ingestion of 13C-glucose.

Fuel selection was measured in five subjects (36.0 +/- 10.5 years old; 87.3 +/- 12.5 kg; mean +/- SD) during a 120-min tethered walking with ski poles (1.12 l O(2) min(-1)) with ingestion of (13)C-glucose (1.5 g kg(-1)), before and after a 20-day 415-km ski trek [physical activity level (PAL) approximately 3], using respiratory calorimetry, urea excretion, and (13)C/(12)C in expired CO(2) and in plasma glucose. Before the ski trek, protein oxidation contributed 9.7 +/- 1.6% to the energy yield (%En) while fat and carbohydrate (CHO) oxidation provided 73.5 +/- 5.5 and 16.7 +/- 6.5%En. Plasma glucose was the main source of CHO (52.9 +/- 9.5%En) with similar contributions from exogenous glucose (27.2 +/- 3.1%En), glucose from the liver (25.6 +/- 8.3%En) and muscle glycogen (20.9 +/- 4.0%En). Endogenous CHO contributed 46.6 +/- 3.9%En. Following the ski trek %En from protein, fat, CHO, exogenous glucose and endogenous CHO were not significantly modified (10.1 +/- 1.3, 15.8 +/- 6.7, 74.1 +/- 6.5, 28.7 +/- 3.0 and 45.5 +/- 7.5%En, respectively) but the %En from plasma glucose and glucose from the liver (41.1 +/- 3.6 and 12.4 +/- 4.0%En) were reduced, while that from muscle glycogen increased (33.0 +/- 4.5%En). These results show that in subjects in the fed state with glucose ingestion during exercise, CHO is the main substrate oxidized, with major contributions from both exogenous and endogenous CHO. Following a ~3-week period of prolonged low intensity exercise, the %En from protein, fat, CHO, exogenous glucose and endogenous CHO were not modified. However, the %En from glucose released from the liver was reduced (possibly due to an increased insulin sensitivity of the liver) while that from muscle glycogen was increased.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs.

Cooling intrathoracic airways by filling the pulmonary circulation with cold blood alters pulmonary mechanoreceptor discharge. To determine whether this initiates reflex changes that could contribute to airway obstruction, we measured changes in tracheal smooth muscle tension and bronchial arterial flow evoked by cooling. In nine chloralose-anesthetized open-chest dogs, the right pulmonary artery was cannulated and perfused; the left lung, ventilated separately, provided gas exchange. With the right lung phasically ventilated, filling the right pulmonary circulation with 5 degrees C blood increased smooth muscle tension in an innervated upper tracheal segment by 23 +/- 6 (SE) g from a baseline of 75 g. Contraction began within 10 s of injection and was maximal at approximately 30s. The response was abolished by cervical vagotomy. Bronchial arterial flow increased from 8 +/- 1 to 13 +/- 2 ml/min, with little effect on arterial blood pressure. The time course was similar to that of the tracheal response. This response was greatly attenuated after cervical vagotomy. Blood at 20 degrees C also increased tracheal smooth muscle tension and bronchial flow, whereas 37 degrees C blood had little effect. The results suggested that alteration of airway mechanoreceptor discharge by cooling can initiate reflexes that contribute to airway obstruction.

A second postcooling afterdrop: more evidence for a convective mechanism.

An attempt was made to demonstrate the importance of increased perfusion of cold tissue in core temperature afterdrop. Five male subjects were cooled twice in water (8 degrees C) for 53-80 min. They were then rewarmed by one of two methods (shivering thermogenesis or treadmill exercise) for another 40-65 min, after which they entered a warm bath (40 degrees C). Esophageal temperature (Tes) as well as thigh and calf muscle temperatures at three depths (1.5, 3.0, and 4.5 cm) were measured. Cold water immersion was terminated at Tes varying between 33.0 and 34.5 degrees C. For each subject this temperature was similar in both trials. The initial core temperature afterdrop was 58% greater during exercise (mean +/- SE, 0.65 +/- 0.10 degrees C) than shivering (0.41 +/- 0.06 degrees C) (P < 0.005). Within the first 5 min after subjects entered the warm bath the initial rate of rewarming (previously established during shivering or exercise, approximately 0.07 degrees C/min) decreased. The attenuation was 0.088 +/- 0.03 degrees C/min (P < 0.025) after shivering and 0.062 +/- 0.022 degrees C/min (P < 0.025) after exercise. In 4 of 10 trials (2 after shivering and 2 after exercise) a second afterdrop occurred during this period. We suggest that increased perfusion of cold tissue is one probable mechanism responsible for attenuation or reversal of the initial rewarming rate. These results have important implications for treatment of hypothermia victims, even when treatment commences long after removal from cold water.

Ventilatory effects of high and pulsatile blood flow in the pulmonary circulation.

The mechanism of ventilatory stimulation that accompanies increases in cardiac output is unknown. Previous studies addressing this issue have been inconclusive. However, only steady pulmonary blood flow was used. The effect of flow pulsatility merits consideration, because increasing cardiac output raises not only mean pulmonary arterial pressure but also pulse pressure; mechanoreceptors with an important dynamic component to their responses may cause a response to pulsatile, but not steady, flow. Studies were done on anesthetized cats (n = 4) and dogs (n = 4). The right pulmonary artery was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the right pulmonary artery. The right pulmonary circulation was perfused at different levels of flow, which was either steady or pulsatile. Steady-state flow of up to 150 ml.kg-1.min-1 (270 ml.kg-1.min-1 when corrected for the proportion of lung tissue perfused) did not affect breathing pattern. When high pulmonary flow was made pulsatile (pulse pressure approximately 23 mmHg), breath duration decreased from 3.7 +/- 0.72 to 3.4 +/- 0.81 (SD) s (P less than 0.01), representing a change in frequency of only 9%. There was no change in peak inspiratory activity. It was concluded that pulmonary vascular mechanoreceptors are not likely to contribute significantly to the increase in ventilation in association with increases in cardiac output.

Ventilatory effect of acute pulmonary hypothermia.

The isolated effect of cooling the pulmonary circulation on ventilation was quantified in nine anesthetized dogs. The right pulmonary artery (RPA) was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the RPA between, but not during, periods of cooling. Cooled blood boluses were injected into the RPA under conditions in which either bolus temperature (5-35 degrees C) or volume (0-1.5 ml/kg body wt) varied. Inspiratory time (TI), expiratory time (TE), breath duration (TT), and peak integrated activity (PEAK) were determined from diaphragm EMG. Results for five postinjection breaths were converted to a percent of the values from five preinjection breaths. There was a linear relationship between bolus temperature and TI [r = 0.61, slope (x) = 0.59%/degrees C, P less than 0.001), TE (r = 0.73, x = 1.43%/degrees C, P less than 0.001] as well as TT (r = 0.74, x = 1.10%/degrees C, P less than 0.001), whereas PEAK was unaffected (n = 9). When injection temperature was 5 degrees C, an inverse linear relationship existed between bolus volume and TI (r = 0.75, x = -15.2%.ml-1.kg-1, P less than 0.001) and TE (r = 0.78, x = -23.4%.ml-1.kg-1, P less than 0.001) (n = 4). In two dogs tested the effect of bolus injection was minimal at residual volume and progressively increased with lung volume. The effect of cold bolus injection was eliminated after right vagotomy in three dogs. Results indicate that cooling of some vagal receptor in the lung increases breathing frequency primarily by shortening TE.

A mathematical model for human brain cooling during cold-water near-drowning.

A two-dimensional mathematical model was developed to estimate the contributions of different mechanisms of brain cooling during cold-water near-drowning. Mechanisms include 1) conductive heat loss through tissue to the water at the head surface and in the upper airway and 2) circulatory cooling to aspirated water via the lung and via venous return from the scalp. The model accounts for changes in boundary conditions, blood circulation, respiratory ventilation of water, and head size. Results indicate that conductive heat loss through the skull surface or the upper airways is minimal, although a small child-sized head will conductively cool faster than a large adult-sized head. However, ventilation of cold water may provide substantial brain cooling through circulatory cooling. Although it seems that water breathing is required for rapid "whole" brain cooling, it is possible that conductive cooling may provide some advantage by cooling the brain cortex peripherally and the brain stem centrally via the upper airway.

Respiratory response to pulmonary vascular congestion in intact conscious dogs.

Clinical disorders associated with pulmonary venous hypertension frequently result in tachypnea and hyperpnea. The response to pulmonary vascular congestion (PVC) in anesthetized or decerebrate animals has consisted of modest and bidirectional changes in respiratory rate with no hyperpnea. We hypothesized that anesthesia or decerebration in previous animal experiments may have attenuated the hyperpneic response that would otherwise have been evident. A conscious dog model was developed in which the left lower lobe (LLL) pulmonary circulation could be reversibly isolated and pressurized. Occluders were placed outside the LLL pulmonary artery (PA) and vein. Two fine catheters were introduced through the wall of the LLLPA distal to the arterial occluder. A pleural catheter was used to monitor pleural pressure swings. After recovery from surgery PVC was initiated by inflation of the occluders and injection of warm saline or fresh warm blood through one of the catheters. PVC resulted in decreased breathing frequency and hypopnea in six of seven intact unanesthetized dogs. The remaining dog exhibited a transient rapid shallow breathing pattern. In four dogs tested using the same preparation under anesthesia, the response to PVC was an increase instead of a decrease in breathing frequency. We conclude that the presence of higher brain function does not promote tachypnea or hyperpnea in response to PVC. Mechanisms other than PVC, per se, likely account for the tachypnea and hyperpnea observed in clinical disorders associated with pulmonary venous hypertension.

Mechanism of detection of resistive loads in conscious humans.

Conscious humans easily detect loads applied to the respiratory system. Resistive loads as small as 0.5 cmH2O.l-1.s can be detected. Previous work suggested that afferent information from the chest wall served as the primary source of information for load detection, but the evidence for this was not convincing, and we recently reported that the chest wall was a relatively poor detector for applied elastic loads. Using the same setup of a loading device and body cast, we sought resistive load detection thresholds under three conditions: 1) loading of the total respiratory system, 2) loading such that the chest wall was protected from the load but airway and intrathoracic pressures experienced negative pressure in proportion to inspiratory flow, and 3) loading of the chest wall alone with no alteration of airway or intrathoracic pressure. The threshold for detection for the three types of load application in seven normal subjects was 1.17 +/- 0.33, 1.68 +/- 0.45, and 6.3 +/- 1.38 (SE) cmH2O.l-1.s for total respiratory system, chest wall protected, and chest wall alone, respectively. We conclude that the active chest wall is a less potent source of information for detection of applied resistive loads than structures affected by negative airway and intrathoracic pressure, a finding similar to that previously reported for elastic load detection.

Short-term effect of tidal pleural pressure swings on pulmonary blood flow during rest and exercise.

Because pleural pressure (Ppl) has important effects on venous return and left ventricular function, it is possible that the magnitude of respiratory fluctuations in Ppl importantly influences cardiac output (pulmonary blood flow, QL) during exercise. To examine this question, we increased (+15 cmH2O) and decreased (-11 cmH2O) the amplitude of fluctuations in Ppl by elastic loading and unloading, respectively, during steady-state exercise (50 W) and estimated the corresponding changes in QL from measurement of breath-by-breath alveolar O2 consumption [(Vo2)A] by a modification of the technique of Beaver et al. (J. Appl. Physiol. 51: 1662-1675, 1981). Load changes were applied for three breaths. Using oscilloscopic volume feedback, subjects maintained constant breathing pattern and end-expiratory volume during control and experimental breaths. This procedure minimized errors in computing (Vo2)A. Furthermore, because over the brief period of load change (especially the first 1 or 2 breaths) mixed venous and arterial O2 contents were not likely to have changed, changes in (Vo2)A reflected changes in QL according to the Fick principle. In six normal subjects, neither loading nor unloading had any effect on (Vo2)A in the first, second, or third breath (P greater than 0.5). Additional studies at rest produced equally negative results. We conclude that the magnitude of respiratory fluctuations in Ppl has no short-term effect on pulmonary blood flow at rest or during mild exercise.

Role of the chest wall in detection of added elastic loads.

Changes in respiratory mechanical loads are readily detected by humans. Although it is widely believed that respiratory muscle afferents serve as the primary source of information for load detection, there is, in fact, no convincing evidence to support this belief. We developed a shell that encloses the body, excluding the head and neck. A special loading apparatus altered pressure in proportion to respired volume (elastic load) in one of three ways: 1) at the mouth only (T), producing a conventional load in which respiratory muscles are loaded and airway and intrathoracic pressures are made negative in proportion to volume, 2) both at the mouth and in the shell (AW), where the same pattern of airway and intrathoracic pressure occurs but the muscles are not loaded because Prs (i.e., mouth pressure minus pressure in the shell is unchanged, and 3) positive pressure in proportion to volume at the shell only, loading the chest wall but causing no change in airway or thoracic pressures (CW). The threshold for detection (delta E50) with the three types of application was determined in seven normal subjects: 2.16 +/- 0.22, 2.65 +/- 0.54, and 6.21 +/- 0.85 (SE) cmH2O/l for T, AW, and CW, respectively. Therefore the active chest wall, including muscles, is a much less potent source of information than structures affected by the negative airway and intrathoracic pressure. The latter account for the very low threshold for load detection.

Ventilatory response to moderate hypoxia in awake chemodenervated cats.

In humans and cats the ventilatory response to 30 min of moderate hypoxia (arterial PO2 40-55 Torr) is biphasic: ventilation increases sharply for the first 5 min and then declines. In humans there is evidence that the decline is dependent on the initial increase. We therefore examined ventilatory responses to moderate isocapnic hypoxia in awake cats with and without carotid body denervation. Cats underwent denervation or a sham operation. Then they were studied in a Drorbaugh-Fenn plethysmograph while ventilation, arterial PO2, and end-tidal PO2 and PCO2 were measured. Three sham-operated and four denervated cats were studied with room air as the control. Sham animals demonstrated a biphasic response: ventilation rose to 211% of control at 5 min and fell to 114% of control at 25 min. Denervated animals showed neither the initial increase nor the subsequent decrease in ventilation. Three sham-operated and three denervated cats were studied with 2% CO2 added to the inspirate. Results were similar: intact cats showed a biphasic response to hypoxia, whereas denervated cats showed neither an increase nor a decrease in ventilation. Preliminary experiments showed that hypoxia was not associated with changes in CO2 output or systemic blood pressure in either denervated or intact animals. We conclude that depression of ventilation does not occur in awake denervated cats in response to moderate hypoxia and that the decline in ventilation that occurs in intact cats is in some way dependent on peripheral chemoreceptor output.

Effectiveness of three field treatments for induced mild (33.0 degrees C) hypothermia.

Three field applicable treatments for hypothermia were compared. Subjects were cooled in stirred cold water (8.0 degrees C) to a core temperature (Tco) as low as 33 degrees C and rewarmed in a random order by each of three techniques: shivering, external heat, and treadmill exercise. Tco was monitored with an esophageal thermistor probe at the level of the heart. Treatment effectiveness was determined by calculating the amount of Tco afterdrop, length of afterdrop period, rate of Tco increase, and total recovery time. Rate of Tco increase for exercise (4.9 degrees C/h) was significantly higher (P less than 0.05) than shivering (3.5 degrees C/h) but not external heat (3.7 degrees C/h). Exercise afterdrop amount and afterdrop length values (0.95 degrees C and 24 min, respectively) were significantly higher (P less than 0.05) than both shivering (0.33 degrees C, 15 min) and external heat (0.32 degrees C, 14 min). Therefore, although rate of Tco increase during recovery for exercise was faster than for shivering or external heat, as it was preceded by a greater afterdrop length and amount, total recovery time did not differ among the three treatments.

Exercise endurance and arterial desaturation in normobaric hypoxia with increased chemosensitivity.

We studied whether exercise endurance under normobaric hypoxia can be enhanced by increasing hypoxic ventilatory sensitivity with almitrine bismesylate (ALM). On both ALM and placebo (PL) days, resting subjects breathed a hypoxic gas mixture (an inspired O2 fraction of 10.4-13.2%), which lowered resting arterial O2 saturation (SaO2) to 80%. After 15 min of rest there was a 3-min warm-up period of exercise at 50 W (light) on a cycle ergometer, followed by a step increase in load to 60% of the previously determined maximum power output with room-air breathing (moderate), which was maintained until exhaustion. With PL, SaO2 decreased rapidly with the onset of exercise and continued to fall slowly during moderate exercise, averaging 71.0 +/- 1.8% (SE) at exhaustion. With ALM, saturation did not differ from PL during air breathing but significantly exceeded SaO2 with PL, by 3.4% during resting hypoxia, by 4.0% at the start of exercise, and by 5.9% at exhaustion. Ventilation was not affected by ALM during air breathing and was slightly, although not significantly, increased during hypoxic rest and exercise. ALM was associated with an increased heart rate during room air breathing but not during hypoxia. Endurance time was 20.6 +/- 1.6 min with ALM and 21.3 +/- 0.9 min with PL. During hypoxic exercise, the potential benefit of greater saturation with ALM is apparently offset by other unidentified factors.

Hypoxia similarly impairs metabolic responses to cutaneous and core cold stimuli in conscious rats.

Cold exposure elicits several thermoregulatory responses, including an increased metabolic heat production from shivering and nonshivering thermogenesis. The increased metabolism can be in response to body core and/or body cutaneous cooling. Hypoxic hypoxia has been shown to attenuate the metabolic response to cutaneous cooling. We measured metabolic heat production in adult conscious rats during independent cutaneous and core cooling, during normoxia and hypoxia, to 1) test the hypothesis that hypoxia suppresses the metabolic response to independent core cooling and 2) determine whether hypoxia acts preferentially on the response to cutaneous or core cooling. The animals were studied in a temperature-controlled metabolic chamber, and body core temperature was controlled by an abdominal heat exchange coil. Ambient temperature was varied (10, 19, and 28 degrees C) while core temperature was clamped at 37 degrees C or core temperature was varied (33, 35, and 37 degrees C) at a stable ambient temperature of 28 degrees C. Our data indicate that although the sensitivity of the metabolic response to core cooling is about five to six times that to cutaneous cooling. Hypoxia similarly attenuates thermoregulatory responses to both stimuli.