Systemic and regional hemodynamics in conscious rats during 24-hour antiorthostatic posture

The systemic and regional hemodynamics during antiorthostatic hypokinesia were studied in male Wistar rats using the radioactive microsphere technique. The animals were hanged up by the tail with the head tilted down (30 degrees) and were able to exercise using only front limbs. Twenty four hours long exposure to antiorthostasis induced significant changes in systemic hemodynamics as well as in regional blood flow in skeletal muscles, spleen, liver and pancreas. Antiorthostasis induced blood flow changes in lungs, heart and brain were less pronounced.     

Transport function of lymph nodes in body antiorthostatic posture

The spontaneous contractile activity of isolated lymph nodes and the lymph flow from intestine lymphatic vessel in antiorthostatic posture of rats with an inclination angle of 30 degrees during 7-14 days, was decreased. Contractions of the rat lymph nodes in response to actions of adrenaline, acetylcholine and histamine were diminished. There are changes of biochemical components of lymph and blood plasma with simultaneous decrease of the blood plasma volume. It is concluded that the lymphatic system on antiorthostatic posture plays the compensatory role with the purpose of stabilization of homeostasis in the brain.     

Contractile activity of pectoral channel and lymph nodes in rats under antiorthostatic influences

It has been established that during short term body antiorthostatic positions lymphatic system carries out compensatory function, unloading the cardiovascular system from redundant exercise. The contractile activity of pectoral channel and lymphatic nodes in weightlessness (antiorthostatic influence) was studied. The functional role of neck lymph nodes is expressed by depositing of liquid during redistribution of the blood. The atony of neck lymph nodes as well as loss of pectoral channel and lymph nodes decrease the receptor sensitivity of vessels and nodes to the action of vasoactive substances.     

Forehead skin microcirculation during tilt table testing and lower body negative pressure

Noninvasive skin microcirculation measurements based on a new Near Infrared sensor technique (NIR/Fa. Silicon Sensor GmbH; Berlin) were embeded in a tilt table experiment for simulation of acute effects of weightlessness (HDT -6 degrees) and active standing with the Russian Tschibis-LBNP device. The phenomenon of orthostatic intolerance depends on complex interactions among functional characteristics of central and peripheral cardiovascular control. The purpose of this study was to assess the blood volume and flow motion changes as well as pulsatile spectral pattern during orthostatic and antiorthostatic stress.     

Effect of the body antiorthostatic posture on various circulation and respiration parameters in anesthetised cats

In anaesthetised cats, antiorthostatic posture of the body with an inclination angle of 30 degrees increased pressure in the vena cava superior and in jugular vein. The rest of the cardio-respiratory parameters were changed insignificantly. Physical and physiological mechanisms of the blood regional redistribution in alteration of the body gravitation orientation, are discussed.     

Evaluation of the liver functional changes in modeling the hemodynamic effects of microgravity in bed rest studies

Ultrasonic examinations of eight male volunteers during bed rest in the antiorthostatic position (ANOP) at–15° showed plethora in the venous system of the abdominal cavity and slow blood flow through the liver with no effect on biochemical parameters. The ¹³C-methcetine breath test (¹³C-MBT) with 100 mg of ¹³C-methoxymethacetine showed diminution of the metabolic capacity and decline in the rate of detoxification activity of the liver due to functional changes related to hemodynamic alterations in ANOP. ¹³C-MBT can be used as a noninvasive method for diagnosing functional changes in the liver induced by hemodynamic reorganization in microgravity and other states triggering similar hemodynamic mechanisms.     

Effect of antiorthostatic suspension on interferon-alpha/beta production by the mouse

Mice were suspended in a model that simulates weightlessness that occurs during prolonged space flight. After 1 and 2 weeks of suspension in an antiorthostatic (head-down tilt) position, the mice were challenged with polyriboinosinic-polyribocytidylic acid to induce interferon-alpha/beta. Interferon production was severely reduced in mice that had been suspended. When mice were allowed to recover in cages for a week following removal from suspension, they recovered their full interferon-production capacity. Mice suspended in an orthostatic (horizontal) position did not have their interferon production capabilities affected, which indicates that stress per se was not a major component in the effects of antiorthostatic suspension on interferon induction.     

Physical working capacity and factors responsible for it after exposure to 120-day antiorthostatic hypokinesia

The effect of 120-day antiorthostatic hypokinesia on human physical working capacity and functional state was studied. The study revealed two adaptation phases: the first phase is characterized by a significant decrease in working capacity and the second by relative readaptation. However, the unfavorable effect of 120-day antiorthostatic hypokinesia was evident as a decrease in the effectiveness of function of the cardiorespiratory system that increased the physiological cost of physical work.     

Cardiovascular Function in Humans Using Thigh Cuffs during Seven Days of Simulated Microgravity

Data are summarized on changes in the human cardiovascular system associated with the use of cuffs during seven days of antiorthostatic hypokinesia simulating weightlessness. Eight subjects participated in two series of experiments, of which one was carried out with and the other (the control) without cuffs wrapped snugly around the upper third of the thighs. The parameters of the systemic hemodynamics, the cardiac function, and the hemodynamics of the cervicocephalic region and the lower limbs recorded under control and experimental conditions were analyzed. Without cuffs, changes in the hemodynamics during antiorthostatic hypokinesia were caused by displacement of body fluids in the cranial direction. The subjects responded favorably to the use of cuffs during antiorthostatic hypokinesia: most of their hemodynamic parameters remained at the baseline level, and signs of venous stasis in the cervicocephalic region were alleviated. Although the leg veins were distended in subjects wearing thigh cuffs during antiorthostatic hypokinesia, no pathological changes in the veins were detected during or after the experiment. Cuff usage during antiorthostatic hypokinesia lasting for seven days did not produce a cumulative effect on the cardiovascular system. These results justify the use of thigh cuffs in the initial period of adaptation to simulated or real weightlessness.     

Physiological Cost of Physical Exercise and Mitochondrial Volume in Working Muscles of Subjects Exposed to Long-Term Hypokinesia: Effects of Local Resistance Exercise

The results of changes in the physiological cost of 30-min submaximal aerobic bicycle ergometric exercise and characteristics of the mitochondrial apparatus of m. vastus lateralis were assessed comparatively during 120-day (–6°) antiorthostatic hypokinesia either without prophylactic measures or with low-intensity resistance exercise training for 60 days using a Penguin exercise suit. Hypokinesia was accompanied by an increase in the working heart rate and lactate accumulation in the blood during the test exercise, as well as by a decrease in the myofibril size and the volume density of mitochondria in the m. vastus lateralis fibers. The patterns of dynamic changes in the lactate concentration in the blood during exercise training and in the volume density of central mitochondria were found to be similar. A correlation between the rate of lactate accumulation in the blood during the test exercise and the volume density of mitochondria in the working muscle appeared after long-term (60 days) exposure to hypokinesia. The use of the Penguin exercise suit in dynamic mode during prolonged (60-day) exposure to hypokinesia completely prevented the following effects: atrophy of slow-type fibers, a decrease in the volume density of central mitochondria, and an increase in the level of lactate accumulation in the blood under conditions of a standard submaximal aerobic exercise load. The correlation links between the oxidative potential of working muscle and the energy supply of muscular work are discussed.     

Functional state of the liver during simulation of the hemodynamic effects of microgravity on the human body

Radioisotope studies of the choleresis function of the liver, ultrasonic studies of the liver and contractile function of the gallbladder and gastroduodenoscopy were carried out in eight subjects after a 24-h stay in a 12° antiorthostatic position (AOP) simulating the hemodynamic changes in the abdominal cavity caused by microgravity. The dynamically hindered venous blood outflow from the liver induced in the AOP model caused activation of choleresis on an empty stomach. This activation manifested itself as an increase in the central perfusion zone of the liver parenchyma, dilation of the biliary ductules, and contraction of the gall-bladder, as well as choleresis into the duodenum. Activation of choleresis in the liver took place against the background of a reduction of the area of radioactive marker distribution in the liver and a decrease in the hepatocyte metabolic activity and the concentration function of the biliary excretion system. The functional characteristics of the liver in the AOP model reflected the reaction caused by changes in its blood content due to the changes in the body position negative to the gravity vector. The mechanism of the changes includes the occurrence of a dynamic venous plethora in the liver; centralization of hepatic blood flow, and activation of choleresis activity against the background of peripheral blood flow depletion, as well as the reduction of metabolic activity of hepatocytes and the concentration function of the biliary excretion system.     

Dynamics of the glycemic profile in women in long-term antiorthostatic hypokinesia

The dynamics of the glycemic curve profile was investigated in 8 healthy women during performance of the glucose tolerance test (GТТ) in 120-day antiorthostatic hypokinesia (–6°) (АNОH) simulating the effects of weightlessness. Glycemic profiles were characterized by more marked hyperglycemic response at 30 min of GТТ in the first month of stay under ANOH conditions and had a flattened appearance three months later. Glycemic profiles characteristic of delayed restoration of the blood glucose concentration appeared in the fourth month, which persisted over the first week after the end of АNОH. The glycemic profile changes developed against the background of the signs of progressive congestion of blood in the venous system of the abdominal cavity. The expansion of diameters of the main veins of the abdominal cavity was noted at the beginning of АNОH; an increase in the size of the organs and the signs of expansion of venous plexuses at the site of portocaval anastomoses, after three months; the occurrence of the signs of transudation and free fluid in the abdominal cavity was revealed at the end of hypokinesia. The countermeasures against hypodynamia did not prevent transformation of the glycemic profile nor did they influence the progression of blood flow congestion in the venous system of the abdominal cavity whose features determined the character changes in the glycemic profile in different periods of ANOH.     

Histological study of brain in the rats exposed to 93-days' tail-suspension

Antiorthostatic position of rats during 93-days' tail suspension induced in the brain strongly pronounced edema of nervous tissue, alteration of structure in horoid plexus, pointing out the decrease in liquor secretion by exocytosis and increase in itraventricular pressure, morphological changes in veins and capillaries, reflecting the development of plethora in veins and tendency to thrombogenesis, and also the appearance of structural signs of prolonged arterial vasoconstriction and narrowing of arterial lumen in surface arteries which be considered as an adaptive process lying the obstacles to excessive blood inflow to brain and dumping the pulse wave during prolonged antiorthostatic state.     

Enhancement of viral pathogenesis in mice maintained in an antiorthostatic suspension model: coordination with effects on interferon production

Both rodents and men returning from spaceflight and the attendent microgravity or weightlessness conditions have exhibited alterations in immune responses and, in particular, interferon production. We have utilized a model for antiorthostatic (20 degrees head-down tilt). hypokinetic, hypodynamic suspension of mice that simulates some aspects of weightlessness. Female Swiss/Webster mice that are normally resistant to infection with the D variant of encephalomyocarditis virus showed a marked increase in susceptibility to infection when suspended. This correlated with a drop in interferon production. Control, orthostatically suspended mice (no head-down tilt) showed no increase in susceptibility to the virus. These data suggest that maintenance of mice in the antiorthostatic suspension model for simulating some aspects of weightlessness yielded increased susceptibility to virus infection that was coincident with inhibited interferon production.     

Emesis, radiation exposure, and local cerebral blood flow in the ferret

We examined the sensitivity of the ferret to emetic stimuli and the effect of radiation exposure near the time of emesis on local cerebral blood flow. Ferrets vomited following the administration of either apomorphine (approx 45% of the ferrets tested) or peptide YY (approx 36% of those tested). Exposure to radiation was a very potent emetic stimulus, but vomiting could be prevented by restraint of the hindquarters of the ferret. Local cerebral blood flow was measured using a quantitative autoradiographic technique and with the exception of several regions in the telencephalon and cerebellum, local cerebral blood flow in the ferret was similar to that in the rat. In animals with whole-body exposure to moderate levels of radiation (4 Gy of 137Cs), mean arterial blood pressure was similar to that in the control group. However, 15-25 min following irradiation there was a general reduction of local cerebral blood flow ranging from 7 to 33% of that in control animals. These cerebral blood flow changes likely correspond to a reduced activation of the central nervous system.     

Cardiovascular effects of centrally administered endothelin-1 and its relationship to changes in cerebral blood flow

Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng, i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (−40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (−46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 μg, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET_A receptors.     

Duration of the hemodynamic effects of N(G)-nitro-L-arginine methyl ester in vivo.

The objective of this study was to quantify the duration of the hemodynamic activity of N(G)-nitro-l-arginine methyl ester (l-NAME) in a variety of different tissues following a single bolus injection of this nitric oxide synthase inhibitor to healthy rats. l-NAME (15 micromol x kg(-1)) was injected (ip) into rats to produce maximal inhibition of endothelial cell NOS. Animals were subsequently anesthetized and blood flow was quantified using the radioactive microsphere/reference organ technique. At 1 h following a single bolus injection of l-NAME blood flow was reduced to the entire gastrointestinal tract, pancreas, and liver. Three hours following l-NAME administration, blood flow to the stomach and upper small intestine had returned to pretreatment levels; however, blood flow to the jejunum, ileal-jejunal junction, and colon remained significantly reduced. Splenic blood flow was significantly reduced and hepatic arterial blood flow was further reduced at this time as well. After 6 h following l-NAME administration, blood flow in all organs had completely recovered to control levels. Although cardiac index and total peripheral resistance had also returned to preinjection values at this time, mean arterial pressure remained elevated at 6 h posttreatment. Blood flow to the brain, lungs, and psoas muscle were unaffected by l-NAME administration at any time point. Taken together, these data demonstrate a differential regulation of vascular tone by NO in different vascular beds and, depending upon the organ system in question, the vasoactive activity of l-NAME may last from 3 to 6 h following a single bolus injection of this NOS inhibitor.     

Limitations imposed by testicular blood flow on the function of Leydig cells in rats in vivo

Testis blood flow per testis closely follows testis weight in rats made aspermatogenic by a single exposure of the testis to 43 degrees C for 30 min or 500 rad (5 Gy) of irradiation from a caesium source, or following ligation of the efferent ducts. Aspermatogenesis following these treatments was associated with only minor changes in the concentrations of testosterone in peripheral blood before stimulation with human chorionic gonadotrophin (hCG), and a reduced responsiveness to hCG when testis weight had fallen after heating. The concentrations of testosterone in testicular venous blood was normal or above normal during aspermatogenesis resulting from heat or irradiation, and only slightly reduced following efferent duct ligation. Consequently testosterone production (defined as the product of plasma flow and the veno-arterial concentration difference for testosterone) was markedly reduced during aspermatogenesis, both before and after stimulation with hCG. It appears that the reduced blood flow limits the amount of testosterone leaving the testis, and while the Leydig cells are capable under some circumstances of compensating partially for this fall by increasing the concentration of testosterone in the testicular venous blood, this compensation is not complete when there are severe reductions in blood flow. Therefore one can conclude that the mass of the tubules is the main determinant of testis blood flow and the Leydig cells must manage with what the tubules require.     

The study of rhythmic changes in the liver hemodynamics by biophysical methods

Data concerning some details of portal blood flow are presented. The following methods for estimations of portal and parenchymal blood flow were used: measuring of perfusion volume velocity--in vitro; flowmetric measuring of blood flow in the portal vein, liver lobe photoplethysmography and bile flow velocity--in situ; photoplethysmography--in vivo. Regular oscillations of portal parenchymal blood flow with the period about 20-90 sec. and synchronous oscillations of the bile flow velocity were found in the above mentioned experiments.