Effect of hemorrhage on blood flow to marrow and osseous tissue in conscious rabbits.

The effect of hemorrhage on blood flow to marrow and osseous tissue was determined in conscious rabbits by injecting radioactive microspheres (15 micron diam) at three time intervals: pretreatment control; 15 min after nonfatal hemorrhage (20 ml/kg body wt), and 16 h posthemorrhage. Cardiac output (CO), blood pressure, heart rate, resistance, arterial PCO2, PO2, and pH, and hematocrit were measured at each time interval. Tissues analyzed included heart, spleen, kidney, and femur with marrow and osseous tissue separated. At 15 min posthemorrhage, CO decreased to all tissues measured except the heart, where it increased. Sixteen hours later, CO returned to normal, and blood flow increased significantly to heart and marrow, while osseous tissue flow returned to control levels. The results show no immediate shunting of blood from bone to marrow; however, after 16 h there is a selective increase in marrow blood flow. This response is only detected by separating marrow and osseous tissue and it may reflect a preparatory mechanism for increased erythropoietic activity.

Hemodynamics in awake rabbits during hyperbaric helium-oxygen exposure.

Although man is being exposed to hyperbaric environments more frequently, the effects of these environments and the inert gases used are not clearly defined. We therefore designed an experiment to examine both the effects of helium and elevated pressure on the cardiovascular system in conscious rabbits exposed to normoxic levels of a helium-oxygen (He-O2) gas mixture at 1 and 11 atmospheres absolute (ATA) for 2 h. Variables studied included heart rate, blood pressure, cardiac output, systemic vascular resistance, organ blood flow, and resistance to flow. The only change observed was a decrease in heart rate from a control of 284 +/- 7 (mean +/- SE) to 246 +/- 12 beats/min after 2 h of breathing He-O2 at 1 ATA. We therefore conclude that the cardiovascular system is not adversely affected by helium or elevated pressure as used in this experiment.

Dye-dilution cardiac output without blood withdrawal in the conscious rabbit.

Cardiac output can be measured in the conscious rabbit without blood withdrawal by use of a modified dye-dilution method. Blood flows continuously from the central ear artery through a Silastic catheter that passes through a modified cuvette lumen and back into an ear vein. Blood flow through this shunt was 1.5 ml/min. This modified technique was evaluated by comparison with a simultaneously performed cardiac output measurement using radioactive microspheres and by making consecutive dye-dilution measurements at short time intervals. A correlation coefficient of 0.96 was obtained when comparing dye-dilution and microsphere cardiac outputs. The difference between 11 paired measurements was 7.09 +/- 5.24% (mean +/- SD). Consecutive outputs measured within 3 min of each other by the flow-through technique had a correlation coefficient of 0.99 and a difference between the first and second determinations of 3.52 +/- 2.38%. The method permits dye-dilution cardiac output measurement in the conscious rabbit while avoiding the potential error caused by blood withdrawal from small animals.

Effect of long-term hyperbaric He-O2 exposure on the weight and histology of endocrine organs in growing rats.

The effects of long-term hyperbaric exposure on endocrine organ weight and histology and on epiphyseal-plate width were studied in growing male rats. Six groups of rats were exposed to 21 ATA He-O2 (200 mmHg O2), and six groups were maintained at 1 ATA as room-air controls. Each group contained eight rats. At intervals of of 2, 3, 5, 8, 10, and 12 weeks, one group was decompressed and studied along with a paired control group. Results indicated no changes in pituitary and adrenal gland weights. Testis weights were variable but histology and sperm content were normal. Only the accessory sex organs decreased significantly in weight; however, prostate and seminal vesicle histology were normal. Tibial epiphyseal-plate width was reduced in 21-ATA groups. These results suggest that long-term hyperbaric exposure has little effect on endocrine organs of the rat and observed weight changes are probably related to the reduced body weights.

Effect of increased oxygen on kidney function in the rat during and after 21 ATA He-O2 exposure.

Two groups of four adult male rats each were exposed continuously for 12 d to 1.2 or 21 ATA He-O2 at 400 mm Hg 02. A third group was maintained under room-air conditions. Urine samples were collected every 12 h for the first 60 h of exposure and for the first 48 h post-decompression. Parameters measured included urine volume, urea, creatinine, calcium, and phosphate. In the 21-ATA group at pressure, urine volume and urea/creatinine increased, and total creatinine decreased; during recovery, total calcium, calcium/creatinine, and urea/creatinine increased and total phosphate decreased. In the 1.2-ATA group, during exposure, urea/creatinine and phosphate/creatinine increased. Diuresis in the 21-ATA group required 48 h to fully develop; however, recovery to normal occurred within 12 h post-decompression. The results reveal a moderate water diuresis and no serious alterations in kidney function during or after 21-ATA exposure at 400 mm Hg O2. There was a mild stress response at pressure and an undefined effect on calcium homeostasis post-decompression.

Selective induction of liver drug-metabolizing enzymes in rats exposed to a 21 ATA He-O2 environment.

The effects of prolonged exposure to a hyperbaric environment (21 ATA He-O2, 200 +/- 300 mm Hg O2, 32.5 +/- 1 degrees C) were investigated on the activity of rat liver drug-metabolizing enzyme systems, as monitored by O-dealkylation and N-dealkylation reactions. Continuous exposure of different groups of rats to a hyperbaric environment for 8, 22, 39, 57, or 84 d significantly increased the in vitro activity of drug-metabolizing enzymes in liver preparations obtained from rats subjected to prolonged exposures. The increase in the in vitro O-dealkylation of p-nitroanisole was selective; and the percent increases were 27, 146, 58, 40, 49, and 44 in liver preparations obtained from rats exposed continuously for 8, 22, 39, 57, 72, or 84 d, respectively. On the other hand, no statistically significant increase was observed in the in vitro activity of rat liver drug-metabolizing enzyme preparations during N-dealkylation of morphine and cocaine.

Skeletal response of growing rats to continuous long-term hyperbaric helium-oxygen exposure.

Bone growth and composition were studied in growing rats following continuous long-term hyperbaric exposure. Six groups of eight rats each were maintained at 21 ATA He-O2 (200 mm Hg O2) and six groups were kept in simulated test chambers under room-air conditions. One group each of pressurized and control animals were removed and analyzed after 2, 3, 5, 8, 10, and 12 weeks. Each animal was weighed and sacrificed. One femur was removed for fresh, dry, ash, and matrix weight measurement and determination of calcium and phosphorus content. The pressurized animals showed a significant reduction in body-weight gain after each exposure period. Femurs from pressurized animals weighed less than controls but had significantly greater femur/body weight percentages. Calcium and phosphorus content was normal and the ratio of matrix to mineral was unchanged. Results suggest that pressurized animals had accelerated metabolic rates and inadequate caloric intake. However, measurements of bone mineral and matrix content indicate the skeleton develops normally under hyperbaric conditions.

Skeletal response of rats to repeated short-term hyperbaric helium-oxygen exposures.

Young male rats were exposed to repeated heliox dives and analyzed for skeletal alterations. Animals were exposed 1, 3, 5, or 7 times to either 1 ATA He-O2 for 12.5 h, or to 5 ATA He-O2 for 4 h and a 8.5 h decompression, or to 5 ATA He-O2 for 4 h and a 1.5 h decompression. In a separate study, 30 rats were exposed 6 times to 5 ATA He-O2 and explosively decompressed. Animals were sacrificed 20 d after the last dive. There were no significant changes in femur wet weight, density, ash weight, length, or mineral content. Plasma calcium, phosphorus, and alkaline phosphatase remained normal. Eighteen of 30 animals survived the six explosive decompressions; however, there were no significant changes in bone. These results indicate that the number and rate of decompressions used in this study have no lasting effect on bone growth and mineral composition in the rat.

Effects of a hyperbaric environment on respiratory and monoamine oxidase activities.

The effects of a prolonged hyperbaric environment (21 ATA He-O2, 200 +/- 30 mm Hg O2, 32.5 +/- 1 degrees C) were investigated on the respiratory activity of rat liver homogenates and the activity of monoamine oxidase in isolated rat-liver preparations. Exposure to a hyperbaric environment for 84 days caused selective in vitro inhibition of nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, D-isocitrate, and alpha-ketoglutarate by rat-liver homogenates. The addition of NAD to the reaction mixture decreased the degree of such an inhibition. No effects on the in vitro activity of liver monoamine oxidase and its inhibition by pheniprazine were observed during exposure of animals to a prolonged high-pressure environment.

Changes in blood flow to bones during the hypocalcemic and hypercalcemic phases of the response to parathyroid hormone.

Labeled microspheres were used to measure blood flow to the leg bones of the laying hen at 0, 3, and 30 min after iv injection of parathyroid hormone (PTH) (Wilson) or the synthetic 1 to 34 fragment of bovine parathyroid hormone (PTH 1-34). At 3 min, which corresponds to the hypocalcemic phase of the PTH response, blood flow to the combined femur, tibia, and metatarus was significantly reduced by PTH (Wilson) relative to 0 time and to carrier-injected controls. At 30 min, i.e., the time of maximum hypercalcemia in the hen, blood flow to these bones was significantly increased relative to 0 time. The results obtained with PTH 1-34 were similar, except that the decrease at 3 min was only significant in comparison with the controls injected with inactivated hormone. Femoral blood flow and the venous minus arterial calcium gradients across the femur were positively correlated, irrespective of sampling time (0 or 30 min) or type of injection (PTH [Wilson] or carrier). Taken together, these results suggest that there is a relationship between calcium mobilization from bone and the rate of osseous blood flow. Other organs which showed significant changes in blood flow after PTH (Wilson) were the adrenals, thyroids, and shell gland; the cerebellum, parathyroids, heart, spleen, liver, pancreas, duodenum, magnum, isthmus, and kidneys were not affected.