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.

Splenic effects on hemodynamics induced by hypothermia and rewarming in miniature swine.

Central arterial hemodynamic changes were assessed during cooling, hypothermia, and rewarming in splenectomized (SPX, n = 4) and unsplenectomized (SP, n = 4) 8-10 month old male Yucatan miniature swine (34.0 +/- 1.4 kg). Under isoflurane anesthesia, and using circulating-water blankets, pigs were cooled to and then maintained for 2 h at a rectal temperature (Tre) of 27 +/- 1 degrees C; hypothermia was followed by rewarming to normothermia (37 +/- 1 degrees C). There were significantly (p < or = 0.05) greater changes in central arterial hematocrit and hemoglobin (delta HCT and delta HGB) from respective precooling baseline levels in the SP group during hypothermia and early rewarming (SP: delta HCTmax = 9-10%RBC, and delta HGBmax = 3.0-3.5 g/dl vs. SPX: delta HCTmax = 3-4%RBC, and delta HGBmax = 1.5-1.8 g/dl). By the end of rewarming, splenic resequestration and extravascular fluid shifts resulted in these values returning to baseline. In addition, cardiovascular instability was seen in the SPX group compared to the SP animals as evidenced by significant tachycardia and hypotension during rewarming. We have concluded from these studies that hypothermia causes significant hemoconcentration, and that splenic contraction is the major cause of this hemoconcentration during hypothermia and initial rewarming in miniature swine. A splenectomized design should be considered for swine studies that purport to pattern human pathophysiology, especially for modelling rewarming shock.

Chronic implantation of nonocclusive catheters and flow probes in the splanchnic and hindlimb vasculature of the rabbit.

Flow probes and nonocclusive catheters were simultaneously implanted in the splanchnic and hindlimb vasculature to measure regional blood flows and arteriovenous differences of individual organs in the conscious rabbit. Pulsed Doppler flow probes were constructed by modifying the technique of Haywood et al., and nonocclusive catheters were designed and constructed from Silastic tubing (0.6- or 0.9-mm OD) and surgical velour. Laparotomy was performed on rabbits under anesthesia, and the renal, mesenteric, iliac, or hepatic artery and portal vein were isolated and instrumented with a flow probe. A nonocclusive catheter was then inserted into the respective vein. Instrumentation of the hepatic system required probes on the hepatic artery and portal vein, and nonocclusive catheters were placed into hepatic and portal veins. One week later, rabbits were reanesthetized and nonocclusive catheters were inserted into the cranial vena cava via the jugular vein and abdominal aorta to the level of the celiac axis. Probes and catheters were evaluated daily up to 30 days. Implants remained functional for an average of 3 weeks, permitting chronic measurement of velocity and blood variables in individual tissue beds of the conscious rabbit.