Effects of almitrine bismesylate in a microswine model of hypoxemic hypothermia.

We have developed an anesthetized microswine model of hypoxemic hypothermia and rewarming for testing prophylaxes and treatments. The respiratory stimulant almitrine bismesylate (ALM) was considered as a potential field expedient therapy for hypoxemic hypothermia. Preliminary experiments demonstrated that five consecutive 100 micrograms.kg-1 ALM intravenous (i.v.) doses given to normothermic microswine 3-4 min apart increased minute ventilation from an average of 3.4 L.min-1 to 4.5 L.min-1 (n = 2). However, when either a single i.v. ALM dose of 150 micrograms.kg-1 (n = 1) or three consecutive 100 micrograms.kg-1 i.v. doses given 15 min apart (n = 1) to hypoxemic hypothermic microswine with a mean esophageal temperature (Tes) = 28.8 degrees C, and a mean arterial O2 partial pressure (PaO2) = 49 mmHg, the hypoxemia was potentiated (mean PaO2 = 32 mmHg) and respiratory arrest ensued. Other experiments using continuous ALM i.v. infusion (1.0 microgram.kg-1.min-1) in hypoxemic hypothermic microswine (n = 6, Tes = 30.6 +/- 0.5, PaO2 = 55.4 +/- 12.9) did not demonstrate significant (p < or = 0.05) cardiorespiratory differences (ventilation, heart rate, blood pressure, blood gases) when compared to hypoxemic hypothermic controls (n = 6, Tes = 30.7 +/- 0.5, PaO2 = 53.3 +/- 13.6). These results suggest that high dose i.v. bolus administration of ALM is not indicated as a potential field expedient therapy for hypoxemic hypothermia, while further work is required to assess the potential efficacy of other continuous low dose i.v. infusion regimens.

A miniswine model of acute exertional heat exhaustion.

METHOD: We examined the thermoregulatory and hemodynamic responses of 12 miniswine (31 +/- 3.9 kg) during 25-30 min of treadmill exercise (5.4 km.h-1, 5% grade) under cool (10 degrees C), moderate (20 degrees C) and warm (30 degrees C) ambient temperature (Ta) conditions. RESULTS: Within 15-20 min of exercise at Ta = 30 degrees C, the miniswine demonstrated significant hyperventilation, hypersalivation, and unsteady gait. Exercise-heat endurance time (T) at Ta = 30 degrees C decreased by 35% and 40% in comparison to T at Ta = 20 degrees C and 10 degrees C, respectively. This resulted from a significant rise in heat strain (S)-defined as the rate of change in rectal temperature. Averaged throughout exercise, S increased from 0.04 +/- 0.01 degree C.min-1 and 0.05 +/- 0.02 degree C.min-1 at Ta = 10 degrees C and 20 degrees C, respectively, to 0.10 +/- 0.03 degree C.min-1 at Ta = 30 degrees C. Due to the comparatively large storage capacity of the porcine spleen relative to humans, splenectomized miniswine were used. This permitted calculation of percentage changes in plasma volume (% delta PVc) from hematocrit (HCT) and hemoglobin (HGB) without the confounding effects of splenic red cells released into the circulation during exercise. Independent of Ta, pre-exercise PVc decreased 3%-5% (p < or = 0.05) within the first 10 min of exercise, but increased 5%-9% (p < or = 0.05) by 10 min post-exercise. CONCLUSION: We conclude that the poor thermoregulatory ability of miniswine manifested in insignificant sweating and restricted evaporative cooling, may make them an appropriate model for acute exertional heat exhaustion in humans working in hot, humid conditions and/or wearing impermeable protective clothing. Further, evaluation of plasma volume changes from HCT and HGB in a miniswine model should consider the merit of a splenectomized design.