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.

Hypothalamic influences on cardiovascular response of beagles to dynamic exercise.

We studied nine young adult beagles at rest and during four levels of dynamic exercise before and after electrolytic lesions were made in the hypothalamus in the region of the fields of Forel. The beagles were habituated to run freely on a motor-driven treadmill and were instrumented chronically to allow repeated measurement of cardiovascular variables. Variables measured or calculated included O2 consumption, cardiac output, arteriovenous O2 difference, systemic arterial pressure, systemic vascular resistance, heart rate, and mixed venous blood lactate concentration. In addition, regional blood flow was measured with radioactive microspheres in two beagles at rest and during peak exercise (6.4 km/h, 20% grade). After prelesion treadmill studies, the beagles were anesthetized and the tips of stainless steel electrodes were placed bilaterally in the hypothalamus in locations that when stimulated (100-300 microA) evoked increases in cardiovascular and muscle motor function. Lesioning (5 mA; 15 s) abolished the responses evoked by stimulation. By contrast, the cardiovascular variables measured in the beagles at rest and during dynamic exercise were similar pre- and postlesion. Therefore, loss of hypothalamic sites that produce increases in cardiovascular and muscle motor function when stimulated electrically does not appear to comprise the cardiovascular response of awake beagles to dynamic exercise.

Regional volume distensibility of canine thoracic aorta during moderate treadmill exercise.

We characterized the in vivo mechanical properties of segments of upper descending thoracic aorta (UDTA) in terms of volume distensibility, which was derived from measurements of pulsatile intravascular pressure, inner wall radius, and length changes. Data for this analysis were obtained from six dogs at rest and during moderate treadmill exercise (8% grade, 4.5 miles/hr). Volume distensibility reflects the regional rheological properties of the UDTA at in vivo states. It was shown to be the sum of circumferential extensibility, longitudinal extensibility, and higher-order extensibilities. Circumferential extensibility and longitudinal extensibility are linear expressions of vessel kinematic changes which represent percent volume changes per pulse pressure and are due to circumferential and longitudinal dimensional changes alone. The higher-order extensibilities (second and third order), however, account for the coupling effect, which is the percentage volume change per millimeter mercury pulse pressure due to the interactions among radial, circumferential, and axial dimensional changes. The volume distensibility of the UDTA during exercise was significantly less than that at rest (0.67 +/- 0.12 vs. 0.91 +/- 0.11% V/mm Hg pressure). This was the result of a significant decrease in circumferential extensibility and higher-order extensibility in response to exercise with no change in longitudinal extensibility. The higher order extensibilities were also important since the volume distensibility of the UDTA was underestimated by 10% for both rest and exercise when they were ignored. We also evaluated radial extensibility by using pressure and wall thickness data and showed that this variable did not change in response to exercise.

Segmental volume distensibility of the canine thoracic aorta in vivo.

Segments of the canine ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta were instrumented with ultrasonic dimension gauges and a cathetertip manometer simultaneously to measure changes in segment diameter, length, and intravascular pressure. Volume distensibility (EV) was calculated as the sum of circumferential extensibility (EC), longitudinal extensibility (EL), and high order extensibilities (EK) for each segment. The EC and EL were linear expressions that represented percentage volume changes per mmHg pulse pressure due to circumferential and longitudinal dimensional changes. The high order extensibilities (second and third order) accounted for the percentage volume changes per mmHg pulse pressure due to the interactions between circumferential and longitudinal dimensional changes. Mean(SEM) EV values from six dogs were 1.62(0.31), 0.84(0.08), and 0.62(0.08)% delta V/mmHg delta P for the ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta segments respectively. The EV, EL, and EK of the ascending aorta segment were significantly greater than those of the upper descending thoracic aorta and middle descending thoracic aorta segments, whereas EC was significantly less in the ascending aorta than in both the upper descending thoracic aorta and middle descending thoracic aorta segments. It is concluded that there are regional differences in aortic distensibility and its components in vivo. Longitudinal wall motion is an important determinant of these aortic mechanical properties.

Plasma volume and estimated liver plasma flow during hyperbaric and hyperoxic exposures in awake dogs.

Five different experiments were conducted to determine if estimated liver plasma flow and/or plasma volume were changed as a result of exposure to 2.8 atmospheres absolute (ATA) while breathing 100% oxygen or 6 ATA while breathing compressed air. The experiments were designed to separate the relative roles of the ambient pressure, the partial pressure of oxygen, the time of high oxygen exposure or some combination of these factors on any observed changes. We found that time was not a factor in the changes seen. Hyperbaria resulted in a decrease in estimated liver plasma flow at all pressures greater than 1 ATA. There was an apparent increase in plasma volume at 1.3 ATA and a return towards 1 ATA values at higher pressures. Hyperoxia resulted in a decrease in estimated liver plasma flow at 975 mm Hg but not at 912 mm Hg. The flow was then increased again at 2128 mm Hg. Plasma volume decreased significantly at 912 mm Hg returned to baseline (152 mm Hg) values at 975 mm Hg and then decreased again at 1054 and 2128 mm Hg PO2.

Trustee survey: trends in board committee structure.

How are changes in the health care environment and in the roles and responsibilities of governing boards affecting board committee structures? This article, based on a recent survey of board chairmen, looks at the latest trends in standing board committees, from which type of committees are most prevalent to recent changes in nonboard membership.

Viscoelastic behavior of the thoracic aorta of dogs and rabbits.

Data are presented which demonstrate no correlation between atrial electrical activity and diameter changes in the descending thoracic aorta of dogs or rabbits. The experiments conducted included bypassing a segment of the descending thoracic aorta in dogs, and production of a variety of arrhythmias without the bypass in dogs and rabbits. We found no evidence of electrical stimulation-induced phasic activity as suggested by other authors.