Christopher L. Chapman

Naloxone prevents interruption of parturition and increases plasma oxytocin following environmental disturbance in parturient sows

Experiments in rodents have suggested that environmental disturbance can disrupt parturition through an opioid-mediated inhibition of oxytocin secretion. To test this hypothesis in a large animal model, 14 primiparous female pigs were allowed to commence parturition in a strawed pen. Five of these gilts were allowed to continue parturition undisturbed in this pen, while the remainder were moved to a farrowing crate immediately after the birth of the first piglet. At this time, pigs were injected subcutaneously with either the opioid antagonist naloxone (n = 4; dose 1 mg/kg body weight) or saline (n = 5). Whereas the undisturbed pigs all gave birth to a second piglet within 53 min, in three of the five disturbed and saline-treated pigs no further births occurred for 2 h, at which time oxytocin was administered subcutaneously to restart parturition. By contrast, all of the naloxone-treated pigs gave birth spontaneously within 2 h, although mean interbirth intervals were still prolonged compared to undisturbed pigs. In a second experiment, nine primiparous female pigs with chronic catheters preplaced in the external jugular vein were similarly moved after the birth of their first piglet and either injected with naloxone (n = 5) or saline (n = 4). Again, parturition was interrupted in three out of four saline-treated animals for at least 2.5 h, but resumed promptly when exogenous oxytocin was administered. Plasma concentrations of oxytocin in these pigs were significantly lower than in naloxone-treated pigs, five out of six of which gave birth spontaneously to one or more piglets within 2.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic responses upon the initiation of thermoregulatory behavior in young healthy adults

ABSTRACT We tested the hypotheses that thermoregulatory behavior is initiated before changes in blood pressure and that skin blood flow upon the initiation of behavior is reflex mediated. Ten healthy young subjects moved between 40°C and 17°C rooms when they felt ‘too warm’ (W→C) or ‘too cool’ (C→W). Blood pressure, cardiac output, skin and rectal temperatures were measured. Changes in skin blood flow between locations were not different at 2 forearm locations. One was clamped at 34°C ensuring responses were reflex controlled. The temperature of the other was not clamped ensuring responses were potentially local and/or reflex controlled. Relative to pre-test Baseline, skin temperature was not different at C→W (33.5 ± 0.7°C, P = 0.24), but was higher at W→C (36.1 ± 0.5°C, P < 0.01). Rectal temperature was different from Baseline at C→W (−0.2 ± 0.1°C, P < 0.01) and W→C (−0.2 ± 0.1°C, P < 0.01). Blood pressure was different from Baseline at C→W (+7 ± 4 mmHg, P < 0.01) and W→C (−5 ± 5 mmHg, P < 0.01). Cardiac output was not different from Baseline at C→W (−0.1 ± 0.4 L/min, P = 0.56), but higher at W→C (0.4 ± 0.4 L/min, P < 0.01). Skin blood flow between locations was not different from Baseline at C→W (clamped: −6 ± 15 PU, not clamped: −3 ± 6 PU, P = 0.46) or W→C (clamped: +21 ± 23 PU, not clamped: +29 ± 15 PU, P = 0.26). These data indicate that the initiation of thermoregulatory behavior is preceded by moderate changes in blood pressure and that skin blood flow upon the initiation of this behavior is under reflex control.

Activation of autonomic thermoeffectors preceding the decision to behaviourally thermoregulate in resting humans

What is the central question of this study? Do increases in metabolic heat production and sweat rate precede the initiation of thermoregulatory behaviour in resting humans exposed to cool and warm environments? What is the main finding and its importance? Thermoregulatory behaviour at rest in cool and warm environments is preceded by changes in vasomotor tone in glabrous and non‐glabrous skin, but not by acute increases in metabolic heat production or sweat rate. These findings suggest that sweating and shivering are not obligatory for thermal behaviour to be initiated in humans.

Thermal behavior remains engaged following exercise despite autonomic thermoeffector withdrawal

We tested the hypothesis that thermal behavior during the exercise recovery compensates for elevated core temperatures despite autonomic thermoeffector withdrawal. In a thermoneutral environment, 6 females and 6 males (22 ± 1 y) cycled for 60 min (225 ± 46 W metabolic heat production), followed by 60 min passive recovery. Mean skin and core temperatures, skin blood flow, and local sweat rate were measured continually. Subjects controlled the temperature of their dorsal neck to perceived thermal comfort using a custom-made neck device. Neck device temperature provided an index of thermal behavior. Mean body temperature, calculated as the average of mean skin and core temperatures, provided an index of the stimulus for thermal behavior. To isolate the independent effect of exercise on thermal behavior during recovery, data were analyzed post-exercise the exact minute mean body temperature recovered to pre-exercise levels within a subject. Mean body temperature returned to pre-exercise levels 28 ± 20 min into recovery (Pre: 33.5 ± 0.2, Post: 33.5 ± 0.2 °C, P = 0.20), at which point, mean skin temperature had recovered (Pre: 29.6 ± 0.4, Post: 29.5 ± 0.5 °C, P = 0.20) and core temperature (Pre: 37.3 ± 0.2, Post: 37.5 ± 0.3 °C, P = 0.01) remained elevated. Post-exercise, skin blood flow (Pre: 59 ± 78, Post: 26 ± 25 PU, P = 0.10) and local sweat rate (Pre: 0.05 ± 0.25, Post: 0.13 ± 0.14 mg/cm2 min-1, P = 0.09) returned to pre-exercise levels, while neck device temperature was depressed (Pre: 27.4 ± 1.1, Post: 21.6 ± 7.4 °C, P = 0.03). These findings suggest that thermal behavior compensates for autonomic thermoeffector withdrawal in the presence of elevated core temperatures post-exercise.

Firefighter Work Duration Influences the Extent of Acute Kidney Injury

Purpose We tested the hypothesis that elevations in biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and dehydration elicited by two common firefighter work durations. Methods Twenty-nine healthy adults (10 females) wearing firefighter protective clothing completed two randomized trials where they walked at 4.8 km·h−1, 5% grade in a 38°C, 50% RH environment. In the short trial, subjects completed two 20-min exercise bouts. In the long trial (LONG), subjects completed three 20-min exercise bouts. Each exercise bout was separated by 10 min of standing rest in an ~20°C environment. Venous blood samples were obtained before and immediately after exercise, and after 1 h recovery. Dependent variables included changes in core temperature, body weight, plasma volume, serum creatinine, and plasma neutrophil gelatinase-associated lipocalin, a marker of renal tubule injury. Results Changes in core temperature (+2.0°C ± 0.7°C vs +1.1°C ± 0.4°C, P < 0.01), body weight (−0.9% ± 0.6% vs −0.5% ± 0.5%, P < 0.01), and plasma volume (−11% ± 5% vs −8% ± 6%, P < 0.01) during exercise were greater in LONG. Increases in creatinine were higher in LONG postexercise (0.18 ± 0.15 vs 0.08 ± 0.07 mg·dL−1, P < 0.01) and after recovery (0.21 ± 0.16 vs 0.14 ± 0.10 mg·dL−1, P < 0.01). Increases in neutrophil gelatinase-associated lipocalin were greater in LONG postexercise (27.0 ± 20.5 vs 12.7 ± 18.0 ng·mL−1, P = 0.01) and after recovery (16.9 ± 15.6 vs 1.5 ± 15.1 ng·mL−1, P = 0.02). Conclusions Biomarkers of acute kidney injury are influenced by the magnitude of hyperthermia and hypovolemia elicited by exercise in the heat.

Peripheral chemosensitivity is not blunted during 2 h of thermoneutral head out water immersion in healthy men and women

Carbon dioxide (CO2) retention occurs during water immersion, but it is not known if peripheral chemosensitivity is altered during water immersion, which could contribute to CO2 retention. We tested the hypothesis that peripheral chemosensitivity to hypercapnia and hypoxia is blunted during 2 h of thermoneutral head out water immersion (HOWI) in healthy young adults. Peripheral chemosensitivity was assessed by the ventilatory, heart rate, and blood pressure responses to hypercapnia and hypoxia at baseline, 10, 60, 120 min, and post HOWI and a time‐control visit (control). Subjects inhaled 1 breath of 13% CO2, 21% O2, and 66% N2 to test peripheral chemosensitivity to hypercapnia and 2–6 breaths of 100% N2 to test peripheral chemosensitivity to hypoxia. Each gas was administered four separate times at each time point. Partial pressure of end‐tidal CO2 (PETCO2), arterial oxygen saturation (SpO2), ventilation, heart rate, and blood pressure were recorded continuously. Ventilation was higher during HOWI versus control at post (P = 0.037). PETCO2 was higher during HOWI versus control at 10 min (46 ± 2 vs. 44 ± 2 mmHg), 60 min (46 ± 2 vs. 44 ± 2 mmHg), and 120 min (46 ± 3 vs. 43 ± 3 mmHg) (all P < 0.001). Ventilatory (P = 0.898), heart rate (P = 0.760), and blood pressure (P = 0.092) responses to hypercapnia were not different during HOWI versus control at any time point. Ventilatory (P = 0.714), heart rate (P = 0.258), and blood pressure (P = 0.051) responses to hypoxia were not different during HOWI versus control at any time point. These data indicate that CO2 retention occurs during thermoneutral HOWI despite no changes in peripheral chemosensitivity.

Behavioral thermoregulation in older adults with cardiovascular co-morbidities

ABSTRACT We tested the hypotheses that older adults with cardiovascular co-morbidities will demonstrate greater changes in body temperature and exaggerated changes in blood pressure before initiating thermal behavior. We studied twelve healthy younger adults (Younger, 25 ± 4 y) and six older adults (‘At Risk’, 67 ± 4 y) taking prescription medications for at least two of the following conditions: hypertension, type II diabetes, hypercholesterolemia. Subjects underwent a 90-min test in which they voluntarily moved between cool (18.1 ± 1.8°C, RH: 29 ± 5%) and warm (40.2 ± 0.3°C, RH: 20 ± 0%) rooms when they felt ‘too cool’ (C→W) or ‘too warm’ (W→C). Mean skin and intestinal temperatures and blood pressure were measured. Data were analyzed as a change from pretest baseline. Changes in mean skin temperature were not different between groups at C→W (Younger: +0.2 ± 0.8°C, ‘At Risk’: +0.7 ± 1.8°C, P = 0.51) or W→C (Younger: +2.7 ± 0.6°C, ‘At Risk’: +2.9 ± 1.9°C, P = 0.53). Changes in intestinal temperature were not different at C→W (Younger: 0.0 ± 0.1°C, ‘At Risk’: +0.1 ± 0.2, P = 0.11), but differed at W→C (-0.1 ± 0.2°C vs. +0.1 ± 0.3°C, P = 0.02). Systolic pressure at C→W increased (Younger: +10 ± 9 mmHg, ‘At Risk’: +24 ± 17 mmHg) and at W→C decreased (Younger: −4 ± 13 mmHg, ‘At Risk’: -23 ± 19 mmHg) to a greater extent in ‘At Risk’ (P ≤ 0.05). Differences were also apparent for diastolic pressure at C→W (Younger: −2 ± 4 mmHg, ‘At Risk’: +17 ± 23 mmHg, P < 0.01), but not at W→C (Younger Y: +4 ± 13 mmHg, ‘At Risk’: −1 ± 6 mmHg, P = 0.29). Despite little evidence for differential control of thermal behavior, the initiation of behavior in ‘at risk’ older adults is preceded by exaggerated blood pressure responses.

The motivation to behaviorally thermoregulate during passive heat exposure in humans is dependent on the magnitude of increases in skin temperature

We tested the hypothesis that the motivation to behaviorally thermoregulate in humans is dependent on the magnitude of changes in mean skin temperature. Ten healthy subjects (22 ± 3 y, 5 females) underwent 60 min of seated rest in a 32±1 °C or 42±1 °C environment (20% relative humidity). Trials were completed in a counterbalanced order. The motivation to behaviorally thermoregulate was measured using an operant behavior task on a fixed ratio schedule, in which subjects received thermal reinforcement after clicking a button 100 times. The reinforcer was 30 s of cooling on the dorsal aspect of the neck. The motivation to behave was defined as the cumulative number of button clicks over time and behavioral thermoregulation was defined as the change in neck skin temperature. Mean skin temperature was higher throughout the 42 °C versus the 32 °C trial (at 60 min: 36.3±0.5 °C vs. 34.5±0.5 °C, P < .01) and core temperature became higher in this trial 40 min into heat exposure (at 60 min: 37.2±0.2 °C vs. 37.1±0.1 °C, P ≤ .04), but did not differ from pre- heat exposure (P = .81). Neck skin temperature was lower in the 42 °C compared to the 32 °C trial starting at 30 min (33.7±0.8 °C vs. 35.3±0.5°C, P < .01), which was maintained thereafter (P ≤ .04). Cumulative responding for thermal reinforcement was greater in the 42 °C trial compared to the 32 °C trial at 20 min (180±155 clicks vs. 0±0 clicks, P < .01), which persisted thereafter (P < .01). These data indicate that the motivation to behaviorally thermoregulate during passive heat exposure in humans is dependent on the magnitude of increases in skin temperature.

Central Chemosensitivity is Augmented during Thermoneutral Head Out Water Immersion in Healthy Adults: 1396 Board #204 May 31 8

Carbon dioxide (CO2) retention occurs during water immersion and increases the risk of CO2 toxicity. The central chemoreceptors primarily mediate the rise in ventilation during hypercapnia. However, it is unknown if two hours of head out water immersion (HOWI) alters central chemosensitivity. PURPOSE: We tested the hypothesis that central chemosensitivity is blunted during two hours of HOWI. METHODS: We assessed central chemosensitivity in 18 subjects (age: 22±1 y, BMI: 25±2 kg/m, 8 women) during a thermoneutral (35±0°C) HOWI trial and a time-control dry trial at baseline, 10 min, 60 min, 90 min, 120 min, and post. The partial pressure of end tidal CO2 (PETCO2; capnograph) and ventilation (pneumotachometer) were recorded continuously. Central chemosensitivity was evaluated via the Read rebreathing test. Briefly, subjects rebreathed 7% CO2 and 93% O2 from a 10 L bag for 3.5 min. Central chemosensitivity was calculated as the slope of the linear regression line of ventilation vs. PETCO2 every 30 s throughout the test. Central chemosensitivity is reported as a change from baseline. RESULTS: PETCO2 was not statistically different during HOWI vs. control at baseline (p=0.90) or post (p=0.27) but was greater during HOWI vs. control at 10 min (45±2 vs. 44±2 mmHg, p=0.02), 60 min (46±1 vs. 44±2 mmHg, p£0.01), 90 min (46±1 vs. 44±2 mmHg, p£0.01), and 120 min (46±1 vs. 44±2 mmHg, p£0.01). Ventilation was not statistically different during HOWI vs. control at baseline (p=0.66), 60 min (p=0.12), 90 min (p=0.12), 120 min (p=0.27), or post (p=0.12) but was greater during HOWI vs. control at 10 min (9.3±2.5 vs. 8.4±1.7 L/min, p=0.05). Change in central chemosensitivity was greater during HOWI vs. control at 10 min (0.7±0.5 vs. 0.0±0.4 L/min/PETCO2, p<0.01), 60 min (0.7±0.7 vs. 0.1±0.3 L/min/PETCO2, p<0.01), 90 min (0.7±0.9 vs. 0.0±0.3 L/min/PETCO2, p<0.01), and 120 min (0.8±1.1 vs. 0.4±0.5 L/min/PETCO2, p<0.01) but was not statistically different during HOWI vs. control at post (p=0.90). CONCLUSIONS: These findings indicate that central chemosensitivity is augmented during two hours of thermoneutral HOWI. Thus, it is unlikely that changes in central chemosensitivity contribute to CO2 retention during water immersion. Fitness and MetS Components Affect Serum-Induced Endothelial Migration and MicroRNAs in

Central chemosensitivity is augmented during 2 h of thermoneutral head‐out water immersion in healthy men and women

What is the central question of the study? Is central chemosensitivity blunted during thermoneutral head‐out water immersion in healthy humans? What is the main finding and its importance? Central chemosensitivity is augmented during thermoneutral head‐out water immersion in healthy men and women. Thus, we suggest that the central chemoreceptors do not contribute to CO2 retention during head‐out water immersion.