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Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness.

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.

Animals↗

Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness.

Rats were tail suspended, keeping their forelimbs weight bearing for 14 days, and then allowed to recover for a short (6-h) or a long (24-h) period to assess the behavior of the sympathetic nervous system after weightless simulation. Sympathetic activity was determined by measuring norepinephrine (NE) turnover in the brain stem cell groups involved in central blood pressure control and in organs playing a key role in the cardiovascular regulation (heart and kidneys). The NE turnover was greatly reduced in the rostral (-56%; P < 0.001) and caudal (-73%; P < 0.001) A2 nucleus of suspended rats but was unchanged in the A1, A5, and A6 cell groups compared with attached rats. The NE turnover in the cardiac atria (-34%; P < 0.001) and ventricles (-35%; P < 0.001) and kidneys (-31%; P < 0.001) was decreased after suspension. The central and peripheral sympathetic activities returned to normal within 24 h of release from suspension, but there was hyperactivity after 6 h of recovery. This raises the problem of interpreting the results obtained in animals killed a few hours after return from spaceflight.

Animals↗

Orthostatic tests after a 4-day confinement or simulated weightlessness.

Besides microgravity, inactivity is likely to play a role in the cardiovascular deconditioning after space flights and weightlessness simulations. The aim of the study was to compare the effects of a 4-day head-down bed rest (HDBR) (-6 degrees) and a 4-day confinement (C) on cardiovascular responses to orthostatic stress. Eight male subjects underwent head-up tilt (HUT) (+60 degrees) and lower-body negative pressure (LBNP) (-20, -30, -40 and -50 mmHg) before (D-1) and at the end (R1) of each situation. Blood pressure, heart rate variability (HRV) and spontaneous baroreflex slope (SBS) were determined. The HDBR reduced orthostatic tolerance, as five subjects presented orthostatic hypotension during the HUT at R1, compared with two subjects at D-1. These same two subjects presented orthostatic hypotension after confinement. The main findings, after HDBR, included reductions in RR interval and total spectral power and a decrease in the parasympathetic indicator (PNS) in favour of a decrease in vagal tone; the increase in the sympathetic indicator (SNS) was not significant. After confinement, the RR interval was also significantly reduced and PNS decreased, but not significantly. RR interval and PNS were further reduced during HUT and LBNP, reflecting a withdrawal of parasympathetic activity. SBS was reduced after HDBR (P < 0.05) and confinement (P = 0.05), with a further reduction during HUT and LBNP without difference between D-1 and R1. This experiment showed that a 4-day HDBR leads to impaired baroreflex function and changes in autonomic balance, which may contribute to orthostatic intolerance. Although less significant, similar patterns of changes in the autonomic nervous system were observed after confinement, suggesting an influence of the inactivity in cardiovascular deconditioning.

Adult↗

Fluid shifts in vascular and extravascular spaces during and after simulated weightlessness.

To simulate weightlessness in a normal-gravity environment, eight male subjects were tilted 5 degrees head-down for 8 h to determine vascular and extravascular shifts of fluid. Most of the initial loss of leg volume during head-down tilt represented a passive shift of venous blood toward the head. Facial edema, headache, nasal congestion, and a pronounced diuresis were associated with this redistribution of blood volume. As measured by the wick-catheter technique during head-down tilt, interstitial fluid pressure in lower-leg muscle and overlying subcutaneous tissues decreased by 7.4 and 4.4 mmHg, respectively. Interstitial fluid was shifted from the lower legs at a rate of 12 ml X h-1. Dehydration of lower-leg tissues probably resulted from decreased capillary blood pressure within these tissues during tilt. Other transcapillary pressures were unchanged. The abrupt alterations in local blood pressure upon changes in body posture were probably sufficient to explain all shifts of vascular and extravascular fluid. In this regard, countermeasures may be necessary to maintain precapillary-muscle tone during long space flights in order to prevent swelling of lower-leg tissues upon readjustment to Earth's gravity.

Airway Obstruction↗

Simulated weightlessness: effects of bioenergetic balance.

As a prelude to a flight experiment, an attempt was made to separate energy requirements associated with gravity from all other metabolic needs. The biological effects of weightlessness were simulated by suspending animals in a harness so that antigravity muscles were not supporting the body. Twelve pairs of rats were allowed to adapt to wearing a harness for 5 d. Experimental animals were then suspended in harness for 7 d followed by recovery for 7 d. Control animals were harnessed but never suspended. VO2, VCO2 and rate of 14CO2 expiration from radio-labeled glucose were monitored on selected days. Food intake and body mass were recorded daily. Metabolic rate decreased in experimental animals during 7 d of suspension and returned to normal during recovery. Although some of the metabolic changes may have related to variation in food intake, simulated weightlessness appears to directly affect bioenergetic balance.

Animals↗

[Thermoregulation under simulated weightlessness].

The effect of simulated weightlessness on thermoregulation was studied in 5 subjects. The experiment consisted of 3d baseline measurements, 7d head-down bed rest and 2d recovery. Circadian rhythm was assessed by continuous measurements of rectal temperature and skin temperature with 2h intervals. Heat Stress Protein 70 (HSP70) was measured by Western-blot Dot method and the facial surface temperature distribution was measured by HR-2 infrared thermography. The results showed that rectal temperature keeps the wake-sleep variation, but the circadian rhythm changed during bed rest, and the change of rectum temperature rhythm appeared mainly in the early-days of bed rest; HSP70 and facial surface temperature increased during bed rest.

Bed Rest↗

[Heat stress-induced HSP70 expression in heart and vessels of simulated weightless rats].

To examine the effect of simulated weightlessness on inducible HSP70 expression in the heart and vessel tissues of rats, a tail-suspension rat model was used to simulate weightlessness. HSP72 mRNA and HSP70 expression in heart and vessel tissues of both simulated weightless and control rats exposed to heat stress (ambient temperature, Ta = 43 degrees C) and recovered at Ta of 25 degrees C for 1 h (CON-H1, SUS-H1) or 2 h (CON-H2, SUS-H2) were analyzed using Northern blot and Western blot. The expression of HSP72 mRNA in the myocardium significantly decreased in SUS-H2, as compared with that of CON-H2 rats. The amount of HSP72 in the myocardium tended to decrease in both SUS-H1 and SUS-H2 groups, as compared with the corresponding control groups, but the differences were not statistically significant. The levels of inducible HSP70 expression in the vessels were related with their anatomical locations, for that the expression of both HSP72 mRNA and HSP72 significantly increased in basilar arteries, whereas it showed a slight decline in femoral arteries. The blunted HSP70 expression in myocardium suggests that simulated weightlessness may induce myocardial changes similar to those in aging. However, the HSP70 expression changes in arteries are in accord with the trend of differential adaptation changes in vessels to simulated weightlessness.

Animals↗

[Energy-metabolism enzymes during combined exposure of the body to simulated weightlessness and gravitational overloads].

Exposure to simulated weightlessness (7-day water immersion and 7-day head-down tilt) caused a decrease in the activity of malate (MDH) and isocitrate dehydrogenase (ICDH), and creatine phosphokinase dehydrogenase (ICDH), and creatine phosphokinase (CPK) at the expense of its MM isoform whereas the activity of alanine (ALT) and aspartate aminotransferase (AST) and pattern of distribution of MDH isoforms remained unchanged. Exposure to acceleration of +3 Gz before and after simulated weightlessness revealed similar changes in the activity of MDH, ICDH, ALT, AST and MDH cytoplasmic fractions. However, the higher increase in the enzyme activity after simulated weightlessness may give evidence for a greater change in cell membrane permeability during acceleration effects that followed simulated weightlessness.

Bed Rest↗

Effects of Chinese herb medicine on improving the circulation of rabbits under simulated weightlessness.

In order to find out the effects of Chinese herb medicine on improving the functional state of blood circulation under weightlessness (WL) or simulated weightlessness (SWL), five experiments (building the SWL animal model and determining the treatment based on the differentiation of symptoms and signs, selecting herb medicine, determining the dosage of Chinese herb medicine, pharmacological text and toxicological experiment of (DH) were accomplished. Two kinds of Chinese herb medicine(CQ and DH) having the effects of improving the circulatory conditions of rabbits in SWL were selected. SWL animal model, space blood stasis and mechanism and effects of Chinese herb medicine were discussed.

Animals↗

Changes in the microstructure of the vestibular apparatus of tadpoles (Rana temporaria) developed in simulated weightlessness.

The vestibular apparatus of tadpoles (Rana temporaria) exposed to simulated weightlessness was examined by electron microscopy. Extended exposure to simulated weightlessness is followed by significant alterations in the sensory epithelia and also in the otolith membrane. Large vacuoles, filled with necrobiotic mitochondria and fragments of endoplasmic reticulum, were concentrated in the region where an otolith membrane covers the hair cells but were mostly absent in zones of the epithelia with undifferentiated cells. The number of otoconia in the otolith membrane was diminished. The results were compared with data from space flight experiments and some concordance was noted. The possible connection between some unusual behavior of the tadpoles after weightlessness simulation and the structural alterations in the gravitational sensors was discussed.

Animals↗

[Changes of brain potentials related to selective mental arithmetic during simulated weightlessness].

To study the effect of simulated weightlessness on brain function state, the brain event-related potentials (ERPs) during a selective mental arithmetic task were compared between head down tilt (HDT) and head up tilt (HUT) in 15 normal subjects. The results were: target (T) flash signals induced significant slow positive potentials and they decreased significantly in amplitude especially during HDT as compared with that during HUT. The data provide new evidence indicating that the ability of brain response declined during simulated weightlessness.

Adult↗

[Changes of brain potentials related to visual attention during simulated weightlessness].

To study the possible effect of simulated weightlessness on brain function state, the brain event-related potentials (ERPs) during a simple visual selective response task were compared between head down tilt (HDT) and head up tilt (HUT) in 9 normal subjects. The results were: both the target (T) and non-target (NT) flash signals induced significant slow positive potentials which were supposed to be related to the attention activity; the amplitude of the positive potentials in the frontal regions decreased significantly especially for NT-ERPs during HDT as compared with that during HUT. The data provide new evidence indicating that the ability of brain response declined during simulated weightlessness and more attention should be paid to the study of brain function during space flight.

Attention↗

Alteration of vasoreactivity of mesenteric arteries in rats after two-week simulated weightlessness.

To investigate the effects of simulated weightlessness on vasoreactivity of mesenteric arteries, rats were tail-suspended for two weeks, and vasoreactivity were studied in vitro using isolated mesenteric arterial ring. The results showed that maximal contractile responses to KCl (10-80 mmol/L) and phenylephrine (PE, 10(-10)-10(-4) mol/L) were attenuated in arterial rings isolated from tail-suspended rats. After constriction caused by 10(-7) mol/L PE, maximal dilatory responses induced by sodium nitroprusside (SNP, 10(-10)-10(-4) mol/L) were not different between tail-suspended and control groups. These data indicated that contractile ability of mesenteric artery was diminished by tail-suspension, whereas the dilatory capacity of arterial smooth muscle was not altered.

Animals↗

[Study on mechanisms of T lymphocyte function changes in mice under simulated weightlessness in terms of IL-2 and Bcl-2 gene transcription].

To understand the mechanisms of T lymphocyte function changes under simulated weightlessness T lymphocyte proliferation (MTT assay), IL-2 production (biological assay), IL-2 gene (dot blot) and Bcl-2 oncogene (RT-PCR) transcription of splenic cell were observed in mice. The results showed that on the 7 th and 14 th day of simulated weightlessness T lymphocyte proliferation and IL-2 production decreased and significant on the 14 th day; on the 7 th and 14 th day of simulated weightlessness IL-2 and Bcl-2 gene transcription decreased, significant on the 14 day. It demonstrated that simulated weightlessness inhibits IL-2 production by decreasing IL-2 gene transcrition. IL-2 and Bcl-2 gene may be regulators of lymphocyte function under simulated weightlessness.

Animals↗

Sympathetic nervous adjustments in man to simulated weightlessness induced by water immersion.

To clarify the role of the sympathetic nervous system to adjust the fluid shift under weightlessness, muscle and skin sympathetic activities were recorded microneurographically in human subjects under simulated weightlessness induced by water immersion up to the levels of the knee, the navel, the breast and the neck. The muscle and skin sympathetic activities were reduced in proportion to rise of immersion level up to the neck. These changes of sympathetic activities were almost concomitant with those of simultaneously recorded soleus electromyograms and heart rate. Reductions of the thigh and the leg circumference were also confirmed by strain gauge plethysmogram recorded under the same experimental condition. Based on these findings, it is concluded that the sympathetic nervous system is suppressed under weightlessness simulated by water immersion. This suppression might depend mainly on the activation of intrathoracic low pressure receptors, due to the fluid shift toward the upper part of the body. The suppression of the sympathetic nervous system seems to be important to compensate the fluid shift under weightlessness.

Adult↗

[Effects of simulated weightlessness on the hypophyseal-cortical-adrenal axis in the pregnant rat].

The eventual part of stress in the hormonal responses to simulated weightlessness was studied during gestation in the rat. We have compared these responses with the effects of two other situations well-known to provoke stress: ultrasounds and denutrition. An increase of blood and adrenal corticosterone levels was found in mothers after denutrition, neither after ultrasounds nor after simulated weightlessness. In foetuses, a decrease of weight was noted after denutrition and simulated weightlessness. Foetal suprarenal corticosterone remained normal when mothers were submitted to simulated weightlessness. In this group, a decrease in foetal weight was found that could be explained by non suprarenal hormonal factors or by circulation disturbances.

Animals↗

Effect of simulated weightlessness on phase II drug metabolism in the rat.

BACKGROUND: Exposure to weightlessness is known to alter physiological processes in humans and animals. As a result of these changes, hepatic drug metabolism may be altered as well. Indeed, short term simulated weightlessness in the rat has been shown to increase oxidative metabolism. HYPOTHESIS: Simulated weightlessness will increase Phase II drug metabolism in the rat during short-term tail suspension. METHODS: The tail-suspended rat model was used to simulate weightlessness. Rats were subjected to 1, 3, 7, or 10 d of tail-suspension in order to mimic the effect of exposure to a microgravity environment. One additional rat group was not suspended and served as a control. On the final day of the study, rats we administered a single intravenous bolus dose of acetaminophen 25 mg x kg(-1) through an implanted jugular catheter and serial blood samples were taken for 90 min. Serum acetaminophen concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters were determined by using standard model independent methods. RESULTS: The results show that simulated weightlessness in the rat has no effect on Phase II drug metabolism, using acetaminophen as a marker compound. CONCLUSIONS: These data support the hypothesis that simulated weightlessness in the rat modulates oxidative metabolism, but not drug conjugation to glucuronide or sulfate metabolites. These data offer insight into the physiological changes and variability seen in hepatic metabolic profiles in humans and animals following actual spaceflight.

Acetaminophen↗

[Effects of simulated weightlessness on T cell subpopulations and activity of IL-2 and IL-6 in mice].

OBJECTIVE: To observe the effects of simulated weightlessness on the immunogenic activities in mice. METHOD: T cell subpopulations and the activity of IL-2 and IL-6 were observed in mice after exposure to head-down (-30 degrees) tail suspension for 3 d and 7 d. RESULT: The activity of IL-2 and IL-6 in mice showed no change after simulated weightlessness for 3 d compared with the control group. But after simulated weightlessness for 7 d, CD3+ and CD4+ were markedly reduced (both P< 0.01) and CD8+ and CD4+/CD8+ also tended to decrease; the activity of IL-2 was significantly decreased, while the activity of IL-6 tended to increase. CONCLUSION: Simulated weightlessness for 7 d had significant effects on T cell subpopulations and the activity of certain cytokines in mice.

Animals↗