Oxygen pre-breathing decreases dysbaric diseases in UW sheep undergoing hyperbaric exposure.

Prolonged exposure of humans and animals to increased pressure as in a disabled submarine (DISSUB) can saturate the body's tissues with dissolved N2 as compressed air is breathed. Decompression-induced bubble formation in the long bone marrow cavity may lead to a bone compartment syndrome resulting in bone ischemia and necrosis. We tested oxygen pre-breathing prior to decompression in sheep to assess the effect upon dysbaric osteonecrosis (DON) induction in a DISSUB simulation experiment. A total of sixteen adult female sheep were used throughout the experiment. Four sheep were used as controls without oxygen pre-breathing. All sheep (99 +/- 14 kg SD) underwent dry chamber air exposure at 60 fsw (2.79 atm abs) (.2827 MPa) for 24 h followed by oxygen (88-92%) pre-breathing (15-min, 1-h, and 2-h and air for control) before "dropout" decompression at 30 fsw/min (0.91 atm/min). 99mTc-methylene diphosphonate (MDP) bone scans of the distal (radii and tibiae) long bones were used to detect "hot spots" of remodeling suggestive of DON lesions. Alizarin complexone fluorochrome was injected to visualize sites of metabolic activity indicating DON repair of both the proximal and distal long bones (radii, tibiae, femora, and humeri). Our findings showed that the amount of alizarin complexone deposition and bone scan uptake was greater in sheep with shorter oxygen pre-breathing times than those undergoing longer pre-breathing dives (p = 0.0056 and p = 0.001, for one and two hour pre-breathes respectively). Proximal limb bones (femur, humerus) displayed less alizarin complexone deposition than the distal radius and tibia (p < 0.0001).

Predicting risk of decompression sickness in humans from outcomes in sheep.

In animals, the response to decompression scales as a power of species body mass. Consequently, decompression sickness (DCS) risk in humans should be well predicted from an animal model with a body mass comparable to humans. No-stop decompression outcomes in compressed air and nitrogen-oxygen dives with sheep (n = 394 dives, 14.5% DCS) and humans (n = 463 dives, 4.5% DCS) were used with linear-exponential, probabilistic modeling to test this hypothesis. Scaling the response parameters of this model between species (without accounting for body mass), while estimating tissue-compartment kinetic parameters from combined human and sheep data, predicts combined risk better, based on log likelihood, than do separate sheep and human models, a combined model without scaling, and a kinetic-scaled model. These findings provide a practical tool for estimating DCS risk in humans from outcomes in sheep, especially in decompression profiles too risky to test with humans. This model supports the hypothesis that species of similar body mass have similar DCS risk.

Dysbaric osteonecrosis in divers and caisson workers. An animal model.

Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.

Experimental respiratory decompression sickness in sheep.

Respiratory decompression sickness (RDCS, "the chokes") is a potentially lethal consequence of ambient pressure reduction. Lack of a clearly suitable animal model has impeded understanding of this condition. RDCS, unaccompanied by central nervous system signs, occurred in 17 of 18 unanesthetized sheep exposed to compressed air at 230 kPa (2.27 ATA) for 22 h, returned to normal pressure for approximately 40 min, and taken to simulated altitude (0.75 ATA, 570 Torr). Respiratory signs, including tachypnea, sporadic apnea, and labored breathing, were accompanied by precordial Doppler ultrasound evidence of marked venous bubble loading. Pulmonary arterial pressures exceeded 30 Torr in five catheterized sheep that died or became moribund. Hypoxemia (arterial Po2 less than 40 Torr), neutropenia, and thrombocytopenia were observed. Peribronchovascular edema was the most prominent necropsy finding. Chest radiography indicated interstitial edema in most affected sheep. High body weight and catheterization predisposed the sheep to severe RDCS. It appears that this protocol reliably provides a useful animal model for studies of RDCS and obstructive pulmonary hypertension, that the precipitating event is massive pulmonary embolization by bubbles, and that venous bubbles, detected by Doppler ultrasound, can signal impending RDCS.

An in vivo technique for the measurement of bone blood flow in animals.

A new technique to measure the in vivo clearance of 41Ar from the bone mineral matrix is demonstrated following fast neutron production of 41Ar in bone via the 44Ca(n, alpha) reaction at 14.1 MeV. At the end of irradiation, the 41Ar activity is assayed with a Ge(Li) detector where sequential gamma-ray spectra are taken. Following full-energy peak integration, background and dead time correction, the activity of 41Ar as a function of time is determined. Results indicated that the Ar washout from bone in rats using this technique was approximately 16 ml (100 ml min)-1 and in agreement with other measurement techniques. For sheep the bone perfusion in the tibia was approximately 1.9 +/- 0.2 ml (100 ml min)-1.

Hydrogen washout in bone cortex and periosteum.

Residence time distributions of hydrogen in bone of anesthetized dogs and rabbits were used to estimate local blood perfusion rates and to characterize the important transport processes taking place. The hydrogen was administered by inhalation, and the concentrations in the bone were measured by embedded platinum microelectrodes. Mean residence times varied significantly both with position and time, and it was found preferable to calculate residence time from moments of the residence time distribution rather than the downslope method. Moreover, the downslope on a semilogarithmic scale continued to decrease with the increase in observation time. For the tissue investigated, simple compartmental models are inadequate even for the small regions characterized by the electrodes. This means that a large number of Haldanian compartments are needed even to characterize local washout behavior. The significance of this finding for the selection of decompression schedules is briefly discussed.

Lack of harmful effects from simulated dives in pregnant sheep.

The purpose of the study was to determine if a near-maximum exposure to air at increased atmospheric pressure causes gross fetal malformations, decreased birth weight, or death when administered to pregnant sheep during peak development of the embryo. Twenty-eight timed-pregnant sheep were alternately assigned to a series of 25- or 30-minute exposures at either 4.6 atmospheres absolute or surface pressure between days 12 and 40 of gestation. About day 130 of pregnancy, 11 experimental and eight control fetuses were recovered, weighed, measured, fixed, and examined for defects. No major structural malformations were present. One minor variation, an undescended testis, occurred in a treated fetus. The results indicate that a series of short, marginally tolerated "dives" by pregnant sheep during peak development does not affect fetal health or survival.