Other studies of small numbers of healthy male volunteers of comparable design have yielded similar results. In one such study (Epstein et al., 1990a), a slight but statistically significant decrease in heart rate was observed but was asymptomatic. In this study the mean age of volunteers was 23.5 years and the eight subjects were preacclimatized.

Epstein and colleagues (1990b) also studied heat exercise performance in eight subjects (mean age 23.5 years) under the added stress of wearing chemical protective clothing. Using a study design similar to those previously described, the volunteers were subjected to 170 minutes of exercise heat stress in protective clothing 4 hours after the fourth 30-mg oral dose of PB. Heart rate, heat storage, and sweat rates were similar in PB- and placebo-treated subjects. Nonevaporative (dry) heat exchange was significantly greater for PB-treated subjects than for controls. The authors concluded that heat stress in subjects wearing chemical warfare (CW) protective garments could lead to severe increases in body heat after 2 hours, but pretreatment with PB did not further decrease exercise performance beyond the limitations presented by heat, exercise, and CW protective clothing.

Wenger and colleagues (1993) studied thermoregulatory effects of dry heat, exercise, and PB treatment in a 7-day, double-blind, crossover study. Seven subjects (mean age 22) received 30 mg PB or placebo every 8 hours and exercised on a treadmill in a dry heat environment. PB increased sweating and evaporative water loss and lowered skin temperature during exercise compared to placebo. PB had no significant effect on rectal (core) temperature, oxygen uptake, or fluid balance. Although PB alone had no significant effect on heart rate, there was an interaction between the day of study and PB treatment on heart rate such that heart rate changed from a decrease of 0.4 beats per minute on day 1 to a decrease of 7.9 beats per minute on day 4. Similar temporal interactions occurred with regard to lowering of skin temperature with exercise. An interaction between increased sweating and treatment day also occurred such that the effect of PB changed from an increase of 0.1 liter of sweat on day 1 to 0.3 liter on day 7. The authors concluded, however, that standard CW prophylactic doses of PB had no clinically significant effect on thermoregulatory response in subjects exposed to exercise and dry heat.

Two studies of PB on thermoregulation during cold exposure were reviewed. Prusaczyk and Sawka (1991) studied the effects of a single 30-mg dose of PB on thermoregulatory responses in six men (mean age 21.8 years) subjected to cold water immersion for up to 180 minutes 2 hours after ingestion of PB or placebo. Cold exposure increased metabolic rate, ventilatory volume, and respiratory rate similarly in PB- and placebo-treated subjects. PB had no significant effects on rectal temperature, mean body temperature, subjective thermal sensations, plasma cortisol levels, or plasma volume. However, severe, but transient, abdominal discomfort caused termination of cold exposure in three of six PB experiments. Investigators concluded that PB did not increase susceptibility to hypothermia but could result in severe abdominal cramping that might limit cold tolerance.

Roberts and colleagues (1994) studied thermoregulatory responses in subjects exposed to exercise and cold air. Seven healthy volunteers (mean age 20)



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