Brown fat and thermogenesis.
Brown adipose tissue providing internal heating jacket and metabolic heater overlying systemic vasculature, noting cold survival role
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Brown adipose tissue providing internal heating jacket and metabolic heater overlying systemic vasculature, noting cold survival role
Using a new Nomex-Lycra elastic fabric and individualized garment engineering techniques, reverse gradient garments (RGG's) were designed, constructed, and tested for effectiveness as a countermeasure against cardiovascular deconditioning. By combining torso-compensated positive pressure breathing with a distally diminishing gradient of counterpressure supplied by the elastic fabric on the limbs, the RGG acts to pool blood in the extremities of recumbent persons much as though they were standing erect in 1 g. It was theorized that through the use of a dynamic pressurization scheme, the RGG would stress the vasculature in a fashion similar to that experienced by the noramlly active man, hence preventing or limiting the development of post-weightlessness orthostatic intolerance and related conditions. Four male, college-age subjects received daily treatments with the RGG during a 15-day bedrest study. Four additional subjects also underwent the bedrest, but received no treatments; they served as controls. The design and construction of the garments are described, and results of the treatment related measurements are given.
A mathematical formulation has been developed to describe the hemodynamic parameters of a conceptualized kidney model. The model was developed by considering regional pressure drops and regional storage capacities within the renal vasculature. Estimation of renal artery compliance, pre- and postglomerular resistance, and glomerular filtration pressure is feasible by considering mean levels and time derivatives of abdominal aortic pressure and renal artery flow. Changes in the smooth muscle tone of the renal vessels induced by exogenous angiotensin amide, acetylcholine, and by the anaesthetic agent halothane were estimated by use of the model. By employing totally implanted telemetry, the technique was applied on unrestrained dogs to measure renal resistive and compliant parameters while the dogs were being subjected to obedience training, to avoidance reaction, and to unrestrained caging.
Decreased cardiothoracic transverse diameter ratios following Mercury, Gemini and Apollo space flights have been reported previously. To evaluate further changes in cardiac size, standard posteroanterior chest films in systole and diastole were obtained before flight and within a few hours after recovery on each of the Skylab astronauts. Postflight chest X-rays were visually compared to the preflight roentgenograms for possible changes in pulmonary vasculature, lung parenchyma, bony or soft tissue structures. From these roentgenograms the following measurements were obtained: cardiac and thoracic transverse diameters, cardiothoracic transverse diameter ratio, cardiac area from the product of both diagonal diameters, cardiac silhouette area by planimetry, thoracic cage area and cardiothoracic area ratio. The postflight frontal cardiac silhouette sizes were significantly decreased when compared with the respective preflight values (P0.05 or 0.01). The observed changes are thought to be related to postflight decrease in the intracardiac chamber volume.
The development of aerospace systems capable of very high levels of positive vertical accelerators stress has created a need for a better understanding of the cardiovascular responses to acceleration. Using a canine model, the heart and cardiovascular system were instrumented to continuously measure coronary blood flow, cardiac output, left ventricular and aortic root pressure, and oxygen saturation in the aorta, coronary sinus, and right ventricle. The animals were exposed to acceleration profiles up to +6 G, 120 s at peak G; a seatback angle of 45 deg was simulated in some experiments. Radiopaque contrast medium was injected to visualize the left ventricular chamber, coronary vasculature, aorta, and branches of the aorta. The results suggest mechanisms responsible for arrhythmias which may occur, and subendocardial hemorrhage which has been reported in other animals.
A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.
Using a new nomex lycra elastic fabric and individualized garment engineering techniques, reverse gradient garments (RGG's) were designed, constructed, and tested for effectiveness as a countermeasure against cardiovascular deconditioning. By combining torso compensated positive pressure breathing with a distally diminishing gradient of counterpressure supplied by the elastic fabric on the limbs, the RGG acts to pool blood in the extremities of recumbent persons much as though they were standing erect in 1 g. The RGG stresses the vasculature in a fashion similar to that experienced by the normally active man, hence preventing or limiting the development of post weightlessness orthostatic intolerance and related conditions. Four male, college age subjects received daily treatments with the RGG during a 15 day bedrest study. Four additional subjects also underwent the bedrest, but received no treatments; they served as controls. The preliminary indication was that the RGG was somewhat effective in limiting the deconditioning process.
The long-term effects on specific animal tissues of exposure to heavy ion irradiation are studied in experiments on cataractogenesis in mice and rabbits. Five groups of rabbits at ages from 8 weeks to 5.3 years were irradiated to a dose of 9.0 Gy of Bragg plateau Ne-20 ions, while mice were exposed to single and total fractionated doses of 4.17 Gy gamma rays or 0.40 to 1.20 Gy of C-12, Ne-20 or Ar-40 particles. Measurements of lens opacities over time show that in the year since irradiation, cataractogenesis is delayed and less severe in rabbits irradiated at age 6 months compared to younger animals, although it is possible that the late effects in adults will surpass those found in the young. The fractionation of the total dose of gamma rays in mice is observed to lead to a marked reduction in the extent of lens opacity after one year, while fractionated heavy ion doses caused a greater degree of posterior lens opacification. Evaluations of the effects of the LET of different ions on cataractogenesis are consistent with RBEs of about 5, 3 and 1-2 for Ar-40, Ne-20 and C-12 ions, respectively. Results thus support the Casarett model of radiation damaging stem cell populations that are not necessarily part of the vasculature.
Alkaline phosphatase is an enzyme found in bone forming cells which decreases in certain bones as a result of hypogravity or non-weight bearing. This enzyme can also hydrolyze adenosine triphosphate. Therefore, an effort was made to localize calcium-stimulated ATPase by cytochemistry to determine whether altered bone cell activity might be related to changing calcium levels which occur during hypogravity. The results indicate that Ca(++)-ATPase is largely found along the endothelium and basal lamina of blood vessels, and not found in bone forming cells. This suggests that calcium regulation in the vicinity of bone formation may be modulated by the vasculature of the area.
The effect of weightlessness on vascular response to orthostatic stress was investigated in human subjects by measuring changes in the arterial pulse volume (APV) of the legs during exposure to lower body negative pressure (LBNP) applied before and after 10 days of continuous 6-deg head-down bed rest. Heart rate, mean arterial blood pressure (MAP), and impedance rheographic indices of APV were measured during rest and at 1 min of -30 mm Hg LBNP. Bed rest was found not to alter the responses of MAP to LBNP. Resting APV was decreased after bed rest; however, APV was reduced upon transfer from rest to 1-min LBPN by the same relative magnitude before and after bedrest. It is concluded that peripheral arterial vasoconstriction, as indicated by reduction in APV during LBNP, is not affected by bedrest. The results suggest that there was no apparent alteration in responsiveness of the leg vasculature following simulated weightlessness, and that the control mechanisms of peripheral resistance do not contribute significantly to reduced orthostatic tolerance following spaceflight.
A study was carried out to determine the time course of residual pulmonary intravascular bubbles after embolization with known amounts of venous air, using an N2O challenge technique. Attention was also given to the length of time that the venous gas emboli remained as discrete bubbles in the lungs with 100 percent oxygen ventilation. The data indicate that venous gas emboli can remain in the pulmonary vasculature as discrete bubbles for periods lasting up to 43 + or - 10.8 min in dogs ventilated with oxygen and nitrogen. With 100 percent oxygen ventilation, these values are reduced significantly to 19 + or - 2.5 min.
Intraocular pressures, retinal vascular diameters, and visual acuities of nine men, were repeatedly measured while the subjects were tilted 10 deg head-down for 48 h and while they were seated before (baseline), and after the tilt. An immediate increase in intraocular pressure, measured by pneumatonometer was recorded when subjects assumed the head-down position, and diurnal variations in intraocular pressures were observed for the 48 h. The initial and final head-down intraocular pressures were not significantly different. However, when subjects resumed the sitting position, intraocular pressures fell below the initial sitting values. Computer image analysis of the retinal vasculature detected a 6 percent and 2 percent reduction in the caliber of arteries and veins, respectively, as compared with sitting baseline values. No changes in visual acuity were documented during the 48 h of head-down tilt. The data suggest that the choroidal blood reservoir increases in volume over 48 h at continuous head-down position with a compensatory decrease in aqueous volume. These findings may explain intraocular pressure changes noted in astronauts during previous space missions and in studies associated with change in body position.
The Soviet biosatellite Cosmos 2044 carried adult rats on a spaceflight that lasted 13.8 days and was intended to repeat animal studies carrier out on Cosmos 1887. Skeletal tissue and tendon from animals flown on Cosmos 2044 were studied by light and electron microscopy, histochemistry, and morphometric techniques. Studies were confined to the bone cells and vasculature from the weight-bearing tibias. Results indicated that vascular changes at the periosteal and subperiosteal region of the tibia were not apparent by light microscopy or histochemistry. However, electron microscopy indicated that vascular influsions were present in bone samples from the flight animals. A unique combination of microscopy and histochemical techniques indicated that the endosteal osteoblasts from this same middiaphyseal region demonstrated a slight (but not statisticallly significant) reduction in bone cell activity. Electron-microscopic studies of the tendons from metatarsal bones showed a collagen fibril disorganization as a result of spaceflight. Thus changes described for Cosmos 1887 were present in Cosmos 2044, but the changes ascribed to spaceflight were not as evident.
The ARGO study investigated the reduced incidence of joint pain decompression sickness (DCS) encountered in microgravity as compared with an expected incidence of joint pain DCS experienced by test subjects in Earth-based laboratories (unit gravity) with similar protocols. Individuals who are decompressed from saturated conditions usually acquire joint pain DCS in the lower extremities. Our hypothesis is that the incidence of joint pain DCS can be limited by a significant reduction in the tissue gas micronuclei formed by stress-assisted nucleation. Reductions in dynamic and kinetic stresses in vivo are linked to hypokinetic and adynamic conditions of individuals in zero g. We employed the Doppler ultrasound bubble detection technique in simulated microgravity studies to determine quantitatively the degree of gas phase formation in the upper and lower extremities of test subjects during decompression. We found no evidence of right-to-left shunting through pulmonary vasculature. The volume of gas bubble following decompression was examined and compared with the number following saline contrast injection. From this, we predict a reduced incidence of DCS on orbit, although the incidence of predicted mild DCS still remains larger than that encountered on orbit.
The presence of gas bubbles in the arterial circulation can occur from iatrogenic mishaps, cardiopulmonary bypass devices, or following decompression, e.g., in deep-sea or SCUBA diving or in astronauts during extravehicular activities (EVA). We have examined the pathophysiology of neurological decompression sickness in human subjects who developed a large number of small gas bubbles in the right side of the heart as a result of hypobaric exposures. In one case, gas bubbles were detected in the middle cerebral artery (MCA) and the subject developed neurological symptoms; a 'resting' patent foramen ovalae (PFO) was found upon saline contrast echocardiography. A PFO was also detected in another individual who developed Spencer Grade 4 precordial Doppler ultrasound bubbles, but no evidence was seen of arterialization of bubbles upon insonation of either the MCA or common carotid artery. The reason for this difference in the behavior of intracardiac bubbles in these two individuals is not known. To date, we have not found evidence of right-to-left shunting of bubbles through pulmonary vasculature. The volume of gas bubbles present following decompression is examined and compared with the number arising from saline contrast injection. The estimates are comparable.
The area postrema in mammals other than rodents and lagomorphs is a bilateral mound of gelatinous-appearing tissue that protrudes into the caudal fourth ventricle on either side of the obex. In rodents and lagomorphs it is a single midline structure at the apex of the calamus scriptorius. The vasculature is derived mainly from the posterior inferior cerebellar arteries and consists mainly of sinusoidal capillaries. It appears to constitute a portal system, at least in the rat. Many of the capillaries are fenestrated, and many large perivascular spaces with both vascular and parenchymal basal laminae are present. The cell population is composed of flattened ependymal cells exhibiting microvilli, and of small neurons, normal astrocytes, glialoid cells, and a very few oligodendroglia. Mast cells are occasionally present. The glialoid cells appear to be the predominant cell type and exhibit great numbers of vascular podia. Axodendritic synapses are numerous and axosomatic synapses are occasionally seen in the parenchyma. Synaptic vesicles are mainly of the clear-cored type but large dense-cored vesicles are commonly observed in some axon terminals.
AS 2 part of the first joint USA-Russian MIR/Shuttle program, fertilized quail eggs were flown on the MIR 18 mission. Post-flight examination indicated impaired survival of both the embryos in space and also of control embryos exposed to vibrational and g-forces simulating the conditions experienced during the launch of Progress 227. We hypothesized that excess mechanical forces and/or other conditions during the launch might cause abnormal development of the blood supply in the chorioallantoic membrane (CAM) leading to the impaired survival of the embryos. The CAM, a highly vascularized extraembryonic organ, provides for the oxygen exchange across the egg shell and is thus pivotal for proper embryonic development. To test our hypothesis, we compared angiogenesis In CAMS of eggs which were either exposed to the vibration and g-force profile simulating the conditions at launch of Progress 227 (synchronous controls), or kept under routine conditions in a laboratory Incubator (laboratory controls). At various time points during Incubation, the eggs were fixed in paraformaldehyde for subsequent dissection. At the time of dissection, the CAM was carefully lifted from the egg shell and examined as whole mounts by bright-field and fluorescent microscopy. The development or the vasculature (angiogenesis) was assessed from the density of blood vessels per viewing field and evaluated by computer aided image analysis. We observed a significant decrease In blood-vessel density in the synchronous controls versus "normal" laboratory controls beginning from day 10 of Incubation. The decrease in vascular density was restricted to the smallest vessels only, suggesting that conditions during the launch and/or during the subsequent Incubation of the eggs may affect the normal progress of angiogenesis in the CAM. Abnormal angiogenesis In the CAM might contribute to the impaired survival of the embryos observed in synchronous controls as well as in space.
In our previous experiments during NASA Shuttle flights SLS 1 and 2 (9-15 days) and EUROMIR flights (30-90 days) we observed that pulmonary blood flow (cardiac output) was elevated initially, and surprisingly remained elevated for the duration of the flights. Stroke volume increased initially and then decreased, but was still above 1 Gz values. As venous return was constant, the changes in SV were secondary to modulation of heart rate. Mean blood pressure was at or slightly below 1 Gz levels in space, indicating a decrease in total peripheral resistance. It has been suggested that plasma volume is reduced in space, however cardiac output/venous return do not return to 1 Gz levels over the duration of flight. In spite of the increased cardiac output, central venous pressure was not elevated in space. These data suggest that there is a change in the basic relationship between cardiac output and central venous pressure, a persistent "hyperperfusion" and a re-distribution of blood flow and volume during space flight. Increased pulmonary blood flow has been reported to increase diffusing capacity in space, presumably due to the improved homogeneity of ventilation and perfusion. Other studies have suggested that ventilation may be independent of gravity, and perfusion may not be gravity- dependent. No data for the distribution of pulmonary blood volume were available for flight or simulated microgravity. Recent studies have suggested that the pulmonary vascular tree is influenced by sympathetic tone in a manner similar to that of the systemic system. This implies that the pulmonary circulation is dilated during microgravity and that the distribution of blood flow and volume may be influenced more by vascular control than by gravity. The cerebral circulation is influenced by sympathetic tone similarly to that of the systemic and pulmonary circulations; however its effects are modulated by cerebral autoregulation. Thus it is difficult to predict if cerebral perfusion is increased and if there is edema in space. Anecdotal evidence suggests there may be cerebral edema early in flight. Cerebral artery velocity has been shown to be elevated in simulated microgravity. The elevated cerebral artery velocity during simulated microgravity may reflect vasoconstriction of the arteries and not increased cerebral blood flow. The purpose of our investigations was to evaluate the effects of alterations in simulated gravity (+/-), resulting in changes in cardiac output (+/-), and on the blood flow and volume distribution in the lung and brain of human subjects. The first hypothesis of these studies was that blood flow and volume would be affected by gravity, but their distribution in the lung would be independent of gravity and due to vasoactivity changing vascular resistance in lung vessels. The vasodilitation of the lung vasculature (lower resistance) along with increased "compliance" of the heart could account for the absence of increased central venous pressure in microgravity. Secondly, we postulate that cerebral blood velocity is increased in microgravity due to large artery vasoconstriction, but that cerebral blood flow would be reduced due to autoregulation.