Work Rate during Self-paced Exercise is not Mediated by the Rate of Heat Storage.

PURPOSE: To date, there have been mixed findings on whether greater anticipatory reductions in self-paced exercise intensity in the heat are mediated by early differences in rate of body heat storage. The disparity may be due to an inability to accurately measure minute-to-minute changes in whole-body heat loss. Thus, we evaluated whether early differences in rate of heat storage can mediate exercise intensity during self-paced cycling at a fixed rate of perceived exertion (RPE of 16; hard-to-very-hard work effort) in COOL (15°C), NORMAL (25°C), and HOT (35°C) ambient conditions. METHODS: On separate days, nine endurance-trained cyclists exercised in COOL, NORMAL, and HOT conditions at a fixed RPE until work rate (measured after first 5 min of exercise) decreased to 70% of starting values. Whole-body heat loss and metabolic heat production were measured by direct and indirect calorimetry, respectively. RESULTS: Total exercise time was shorter in HOT (57 ± 20 min) relative to both NORMAL (72 ± 23 min, P = 0.004) and COOL (70 ± 26 min, P = 0.045). Starting work rate was lower in HOT (153 ± 31 W) compared with NORMAL (166 ± 27 W, P = 0.024) and COOL (170 ± 33 W, P = 0.037). Rate of heat storage was similar between conditions during the first 4 min of exercise (all P > 0.05). Thereafter, rate of heat storage was lower in HOT relative to NORMAL and COOL until 30 min of exercise (last common time-point between conditions; all P < 0.05). Further, rate of heat storage was significantly higher in COOL compared with NORMAL at 15 min (P = 0.026) and 20 min (P = 0.020) of exercise. No differences were measured at end exercise. CONCLUSIONS: We show that rate of heat storage does not mediate exercise intensity during self-paced exercise at a fixed RPE in cool to hot ambient conditions.

The physical demands of electrical utilities work in North America.

We assessed the physical demands associated with electrical utilities work in North America and how they influence the level of thermal and cardiovascular strain experienced. Three common job categories were monitored as they are normally performed in thirty-two electrical utility workers: (i) Ground Work (n = 11), (ii) Bucket Work (n = 9), and (iii) Manual Pole Work (n = 12). Video analysis was performed to determine the proportion of the work monitoring period (duration: 187 ± 104 min) spent at different levels of physical effort (i.e., rest as well as light, moderate and heavy effort). Core and skin temperatures as well as heart rate were measured continuously. On average, workers spent 35.9 ± 15.9, 36.8 ± 17.8, 24.7 ± 12.8, and 2.6 ± 3.3% of the work period at rest and performing work classified as light, moderate, and heavy physical effort, respectively. Moreover, a greater proportion of the work period was spent performing heavy work in Ground Work (1.6 ± 1.4%) relative to Bucket Work (0.0 ± 0.0%; P<0.01) and in Manual Pole Climbing (5.5 ± 3.6%) in comparison to both other work job (both P≤0.03). Furthermore, the proportion of time spent during work classified as heavy physical effort was positively correlated to the mean (r = 0.51, P<0.01) and peak (r = 0.42, P = 0.02) core temperatures achieved during the work period as well as the mean heart rate response (presented as a percentage of heart rate reserve; r = 0.40, P = 0.03). Finally, mean and peak core temperatures and mean heart rate responses increased from the first to the second half of the work shift; however, no differences in the proportion of the work spent at the different intensity classifications were observed. We show that Manual Pole Work is associated with greater levels of physical effort compared to Ground or Bucket Work. Moreover, we suggest that the proportion of time spent performing work classified as heavy physical exertion is related to the level of thermal and cardiovascular strain experienced and that workers may not be employing self-pacing as a strategy to manage their level of physiological strain.

An Evaluation of the Physiological Strain Experienced by Electrical Utility Workers in North America.

The purpose of this study was to assess the physiological strain experienced by North American electrical utility workers during the performance of their normal work duties in heat stressed conditions. Three common job categories were monitored as they are normally performed in 32 electrical utility workers: (i) Ground Work (n = 11); (ii) Bucket Work (n = 9); and (iii) Manual Pole Work (n = 12). Worker hydration status (urine specific gravity (USG)) was measured prior to and following the work monitoring period (duration: 187 ± 104 min). Core and skin temperatures as well as heart rate were measured continuously. Physiological Strain Index (PSI) was calculated from the measurements of core temperature and heart rate. Prior to the start of the work shift, 38% of workers were euhydrated (USG < 1.020; n = 12) whereas the majority of workers were dehydrated (USG > 1.020; prevalence: 75%; p < 0.01) following work. The overall mean and peak core temperatures for all monitored workers were 37.9 ± 0.3 °C and 38.3 ± 0.5 °C, respectively. When responses were compared between job categories, greater mean and peak increases in core temperature were observed in Manual Pole Work relative to the other job categories (both p < 0.04). In fact, six workers performing Manual Pole Work achieved core temperatures in excess of 38.5 °C, while only one other worker surpassed this threshold in Bucket Work. The high levels of thermal strain were paralleled by elevated mean and peak heart rate and PSI responses, which were greater in Manual Pole Work in comparison to the other job categories (all p ≤ 0.05). Furthermore, two workers performing Manual Pole Work achieved severely elevated core temperatures reaching or exceeding 39.5 °C along with prolonged periods of near maximal heart rate responses (i.e., >90% of heart rate reserve). We report elevated levels of thermal and cardiovascular strain in electrical utility workers during work in the heat and potentially dangerous levels of hyperthermia during particularly strenuous work.

Comparison of the safety and pharmacokinetics of ST-246® after i.v. infusion or oral administration in mice, rabbits and monkeys.

BACKGROUND: ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v.) formulation may be required for some hospitalized patients who are unable to take oral medication. An i.v. formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. METHODOLOGY/PRINCIPAL FINDINGS: The pharmacokinetics of ST-246 after i.v. infusions in mice, rabbits and nonhuman primates (NHP) were compared to those obtained after oral administration. Ten minute i.v. infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short i.v. infusions (5 to 15 minutes) in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and i.v. infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C(max) plasma concentrations. These effects were eliminated using slower i.v. infusions. CONCLUSIONS/SIGNIFICANCE: Pharmacokinetic profiles after i.v. infusion compared to those observed after oral administration demonstrated the necessity of longer i.v. infusions to (1) mimic the plasma exposure observed after oral administration and (2) avoid C(max) associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and i.v. administration. The administration of ST-246 was well tolerated as a slow i.v. infusion.