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At least 145 records · Page 8

Hemopoiesis in the pig-tailed monkey Macaca nemestrina during chronic altitude exposure.

Study of monkeys for 180 days at 3800 m altitude to examine their hemopoietic response. Plasma volume was found to be reduced while red cell volume increased steadily for four to five months. Reduction in mean corpuscular hemoglobin content was observed from day 30 to day 120 at altitude. Total plasma protein concentration was unchanged at altitude, but marked reduction in the albumin/globulin ratio occurred. Total circulating plasma protein and albumin were reduced in amount, whereas nonalbumin protein was unchanged. These results imply loss of albumin coupled with a corresponding loss of water from the blood and maintenance of normal plasma osmotic pressure. The body/venous hematocrit ratio was found to be reduced at altitude, possibly as a consequence of the expanded capillary volume of the body. The hemopoietic responses of the pig-tailed monkey at altitude require at least several months for completion, and closely resemble those seen in man; thus, the monkey can serve well for long-term studies of high-altitude acclimatization.

Buderer, M. C.↗

Immune alterations in male and female mice after 2-deoxy-D-glucose administration

Administration of 2-deoxy-D-glucose (2-DG) induces acute cellular glucoprivation. In the current study, we examined differences in immune parameters after 2-DG administration in both sexes. Male and female BDF1 mice were injected three times, 48 h apart, either with a saline solution (control group) or with 2-DG in saline (500 mg/kg). Two hours after the last injection, blood and spleens were collected. Plasma levels of interleukin-1beta, and interferon-gamma levels were measured. Additionally, the levels of the specific leukocyte antigens CD3, CD4, CD8, T cell receptor (TCR) alpha/beta, I-Ad, and H-2Ld/H-2Db were evaluated by flow cytometry on both blood and spleen cells. The blastogenic response of leukocytes from both tissues to mitogens was assessed. Levels of glucose, corticosterone, testosterone, progesterone, 17beta-estradiol, follicle-stimulating hormone, and luteinizing hormone were also determined. Increases in the percentage of cells bearing TCR alpha/beta and I-Ad in the blood and H-2Ld/H-2Db in the spleen were observed in the 2-DG-treated group for both sexes. In contrast, higher corticosterone and IL-1beta plasma concentrations, as well as higher percentages of splenocytes bearing TCR alpha/beta and I-Ad, and lower mitogen-induced proliferation of mature T splenocytes (79%) were observed in female but not in male mice injected with 2-DG compared with those injected with saline (p < 0.05). Taken together, these results suggest that female mice are more sensitive than male mice to immune alterations induced by 2-DG administration.

Non-NASA Center↗

Paraventricular Stimulation with Glutamate Elicits Bradycardia and Pituitary Responses

The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (-80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 pA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.

Darlington, Daniel N.↗

Plasma volume, renin, and vasopressin responses to graded exercise after training

Four male subjects underwent a series of ergometer trials to test the hypothesis that training-induced hypervolemia produces a reduction in the relative change of plasma volume, vasopressin, and renin activity levels. Sitting ergometer exercise was performed for 2 hr per day for 8 consecutive days and the VO2 was monitored. A second phase involved a graded exercise and recording of the VO2 and HR, as well as the taking of blood samples to measure the plasma osmolality, the vasopressin content, and the renin activity. The training was found to reduce the plasma volume levels for a given work load. Hypervolemia was induced by a training-produced plasma volume expansion. The osmolality, vasopressin content, and renin activity increased with training. A threshold work intensity of 50 percent was identified for changes in the osmolality and the stimulation of renin activity and vasopressin increase. The maintenance of a certain level of intensity during training is concluded necessary to stimulate the hypervolemic response.

Convertino, V. A.↗

Plasma thyroxine changes of the Apollo crewmen

Blood drawn from Apollo crew members prior to the mission, at recovery, and postmission, was used to examine the effect Apollo mission activities have on thyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that Apollo activities and environment caused the postmission increase in plasma thyroxine. The prolonged postmission decreases in serum cholesterol may be one result of the increased thyroxine activity.

Sheinfeld, M.↗

Fluid shifts and endocrine responses during chair rest and water immersion in man

The effects of external water pressure on intercompartmental fluid volume shifts and endocrine responses in man are investigated. Extracellular fluid volumes and plasma and urine electrolyte and endocrine responses of four male subjects were measured during eight hours of head-out water immersion and 16 hours of recovery bed rest and compared to responses obtained during eight hours of chair rest and 16 hours of bed rest without external hydrostatic pressure obtained in the same subjects five months later. Immersion is found to result in a substantial diuresis with respect to chair rest, accounted for by decreases in extracellular volume. A negative water balance during immersion and a positive water balance during chair rest were observed to be accompanied by a shift of extracellular volume to the intracellular compartment, as well as the suppression of plasma arginine vasopressin and renin activities in both regimes. The vasopressin and renin activity decreases are attributed to the increased central blood volume, and half of the plasma loss in immersed subjects is attributed to the effects of external water pressure.

Greenleaf, J. E.↗

Periodic upright posture negates the suppression of neuroendocrine response to head down bedrest

Head down bedrest (HDT) decreases plasma neurohormone levels, attaining a nadir within four hours. The present study evaluates the effect of periodic standing or exercises (+G(z)) on this acute suppression of plasma neurohormones. Methods: Nine male subjects (mean plus or minus SE age 37 plus or minus 2 yr; height 182 plus or minus 2 cm; weight 83 plus or minus 3 kg) were admitted to the Human Research Facility on three occasions separated by one month. Subjects were assigned to head down tilt (minus 6 degrees) or 15-minutes of standing or moderate exercise at the end of each hour. Initially during an ambulatory period, subjects were placed in a supine position for 45-min and a control blood sample obtained. The next day following 4 hours of HDT with or without standing or exercise a blood sample was taken 45-min (3 3/4 hours into HDT) after the preceding stand or exercise. Blood was withdrawn and all plasma samples frozen for determination of neurohormone levels within the same assay. Plasma aldosterone, Plasma Renin Activity (PRA) vasopressin (AVP) and cortisol levels were measured by radioimmunoassay. Norepinephrine (NE) and epinephrine (E) levels were measured by electrochemical detection following HPLC. Values were compared by ANOVA, P less than 0.05. Results: Control levels following 45-min supine were not different between treatments. HDT suppressed plasma aldosterone (13.9 plus or minus 3.7 to 6.6 plus or minus 0.7 ng/dl) and NE levels (299 plus or minus 35 to 217 plus or minus 23 pg/dl), E (69 plus or minus 15 to 65 plus or minus 21 pg/ml), and PRA (0.64 plus or minus 0.13 to 0.58 plus or minus 0.17 ngAl/m/hr) were not significantly altered. Standing or exercise negated the decrease in aldosterone and NE levels due to HDT. Conclusions: Periodic upright posture (+G(z)) with or without exercise for 15-min out of each hour negates the acute suppression of aldosterone and NE associated with HDT.

Wade, C. E.↗

Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

Convertino, V. A.↗

Disproportional changes in hematocrit, plasma volume, and proteins during exercise and bed rest.

The interrelationships between the changes in plasma volume, hematocrit, and plasma proteins during muscular exercise and bed rest were investigated. Proportionally, the changes in hematocrit are always smaller than the changes in plasma volume. For this reason changes in the concentration of blood constituents can only be quantitated on the basis of plasma volume changes. During short periods of intensive exercise, there was a small loss of plasma proteins. With prolonged submaximal exercise there was a net gain in plasma protein, which contributes to stabilization of the vascular volume. Prolonged bed rest induced hypoproteinemia; this loss of plasma protein probably plays an important role in recumbency hypovolemia.

Van Beaumont, W.↗

Beta-Adrenergic Blockade Does not Prevent Polycythemia or Decrease in Plasma Volume in Men at 4300 m Altitude

When humans ascend to high altitude (ALT) their plasma volume (PV) and total blood volume (BV) decrease during the first few days. With continued residence over several weeks, the hypoxia-induced stimulation of erythropoietin increases red cell production which tends to restore BV. Because hypoxia also activates the beta-adrenergic system, which stimulates red blood cell production, we investigated the effect of adrenergic beta-receptor inhibition with propranolol on fluid volumes and the polycythemic response in 11 healthy unacclimatized men (21-33 years old exposed to an ALT of 4300 m (barometric pressure 460 Torr) for 3 weeks on Pikes Peak, Colorado. PV was determined by the Evans blue dye method (PV(sub EB)), BV by the carbon monoxide method (BV(sub CO)), red cell volume (RCV)was calculated from hematocrit (Hct) and BV(sub CO), and serum erythropoietin concentration ([EPO]) and reticulocyte count, were also determined. All determinations were made at sea level and after 9-11 (ALT-10) and 9-20 (ALT-20) days at ALT. At sea level and ALT, six men received propranolol (pro, 240 mg/day), and five received a placebo (pla). Effective beta-blockade did not modify the mean (SE) maximal values of [EPO] [pla: 24.9 (3.5) vs pro: 24.5 (1.5) mU/ml] or reticulocyte count [pla: 2.7 (0.7) vs pro: 2.2 (0.5)%]; nor changes in PV(sub EB)[pla: -15.8 (3.8) vs pro: -19.9 (2.8)%], RCV(sub CO) [pla: +7.0 (6.7) vs pro: +10.1 (6.1)%], or BV(sub CO) [pla: -7.3 (2.3) vs pro: -7.1 (3.9)%]. In the absence of weight loss, a redistribution of body water with no net loss is implied. Hence, activation of the beta-adrenergic system did not appear to affect the hypovolemic or polycythemic responses that occurred during 3 weeks at 4300 m ALT in these subjects.

Grover, R. F.↗

Potentiation of Hormonal Responses to Hemorrhage and Fasting, but not Hypoglycemia in Conscious Adrenalectomized Rats

Bilateral adrenalectomy (ADRX) in rats removes the source of two major stress-responsive hormones, corticosterone and epinephrine. To test how ADRX rats with-stand stress, we performed the following experiments in adult male rats provided with indwelling femoral arterial and venous cannulae and either ADRX or sham-adrenalectomized (Sham) 3 days later and given 0.5% NaCl to drink. Five to 6 days after adrenal surgery the rats were studied after either a 15 ml/kg.5 min hemorrhage or after an overnight fast followed by insulin-induced hypoglycemia. In fed unstressed ADRX rats, basal mean arterial blood pressure was slightly decreased; heart rate was increased; blood volume, vasopressin, and oxytocin concentrations were not different from sham values; and renin and norepinephrine were significantly elevated. The recovery of arterial pressure after hemorrhage in the ADRX rats was similar to that in the sham group over a 5-h period; however, the responses of vasopressin and oxytocin were significantly greater, and those of renin and norepinephrine were markedly potentiated in the ADRX group. Heart rate recovered faster in the ADRX group and was elevated, compared to the sham value, for most of the 5-h period. Restitution of blood volume was attenuated in the ADRX group, although the restitution of plasma protein was not different between the groups. A significant difference in the change in plasma osmolality between groups after hemorrhage may account for the attenuated restitution of blood volume. After an overnight fast, which reduced blood volume in both groups of rats, the plasma renin concentration rose still further in ADRX rats; the differences in other measured variables observed between fed ADRX and sham groups remained the same. The insulin-induced 50% decrease in glucose caused minor effects on arterial blood pressure and heart rate and occasioned responses in renin and norepinephrine of similar magnitudes in the two groups. We conclude that in the absence of the adrenals, rats restore arterial pressure after hemorrhage remarkably well through potentiation of the responses of other vasoactive neural and hormonal systems. In these studies the marked potentiation of the renin response suggests that the renin-angiotensin system may be important in the maintenance of arterial blood pressure after reductions in blood volume.

Darlington, Daniel N.↗

Comparative changes in plasma protein concentration, hematocrit and plasma volume during exercise, bedrest and + Gz acceleration.

Discussion of experiments which indicate that under conditions of a constant red cell volume the proportional changes in hematocrit and plasma volume during exercise are never equal. On the basis of direct measurements and calculated changes of plasma volume it is concluded that during maximal exercise there is a small loss of protein from the plasma. It is clear that changes in content of blood constituents can only be evaluated correctly after determination of changes in plasma volume.

Van Beaumont, W.↗

Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

Non-NASA Center↗

Fed, but not Fasted, Adrenalectomized Rats Survive the Stress of Hemorrhage and Hypovolemia

We have recently shown that conscious adrenalectomized rats exhibit nearly normal recovery of arterial blood pressure during the 5 h after hemorrhage. In those experiments, it appeared that a previous reduction in food intake might have compromised the recovery of blood pressure and increased mortality. These experiments were designed to test in conscious sham-adrenalectomized (control) and adrenalectomized rats prepared with indwelling arterial and venous cannulae: 1. The effects of a 20- to 24-h fast (compared to rats fed ab libitum) on the mobilization of plasma substrates and recovery of arterial blood pressure after a 15 ml/kg - 5 min hemorrhage, and 2. Vascular responsivity to pressor agents in fed or fasted groups before or 2 h after hemorrhage. In all rats hemorrhage resulted in decreased arterial pressure and heart rate. Arterial pressure recovered to near normal in both fed and fasted control groups and in the led adrenalectomized rats, and all of these rats survived for 24 h after stress. By contrast, in the fasted adrenalectomized rats, arterial pressure recovered only during the first 1.5 - 2 h and then failed, resulting in 100% mortality by 3-5 h. Compared to the other three groups, in which substrate levels either increased or remained fairly stable, plasma glucose and beta-hydoxybutyrate concentrations fell steadily, from 1.5-2 h after hemorrhage until death occurred in the fasted adrenalectomized rats. Basal ACTH concentrations were elevated cormpared to control values in both adrenalectomized groups (fed and fasted). Hemorrhage caused increases in plasma ACTH in all groups; the magnitude of the responses did not differ among the groups. The dilution of Evans' blue dve after hemorrhage (used as an index of fluid movement into the vascular space) was not different in contol and adrenalectomized rats (either fed or fasted). There were no differences in pressor responses to phenylephrine, vasopressin, or angiotensin-II between the fed and fasted condition in the control rats either before or after hemorrhage. There was a fasting-associated decrease in vascular responsivity, to vasopressin, but normal responsivity to phenylephrine and angiotensin-II, in the adrenal-ectomized rats both before and after hemorrhage. We conclude that: (1) since fed adrenalectomized rats all survived the stress, adrenal hormones are not required for survival unless fasting is a prior condition; (2) vascular responsiveness to phenylephrine and angiotensin-II is not altered by fasting and is, therefore, probably not the proximate cause of cardiovascular svstem failure; and (3) from these data we cannot distinguish between a failure in substrate supply and a failure in some component of the cardiovascular svstem, other than vascular responsivity, that results in death after hemorrhage in fasted adrenalectomized rats.

Darlington, Daniel N.↗

Leucocytosis, Thrombocytosis, and Plasma Osmolality During Rest and Exercise: A Hypothesis

The mechanism for inducing leucocytosis (increase in white blood cells) and thrombocytosis (increase in platelets) during exercise is unclear. Because plasma osmolality (Osm) may influence T-cell proliferation, Osm and the number of leucocytes (WBC) and platelets in blood were measured periodically during a 90 min rest period, and were compared with those during upright sitting ergometer exercise in six unt.rained, healthy men who cycled for 70 min at 71% of their maximal oxygen uptake (V prime O(sub 2(sub max)). There were 6 experiments in which the subjects drank different fluid formula-t4ilons (10 ml/kg) of various ionic and osmotic concentrations intermittently during 60 min of the rest period and during the exercise period. Osmolality, and WBC and platelet counts increased significantly (p<0.05) within the first 10 min of exercise, but the additional 60 min of exercise did not significantly change the leucocytosis or thrombocytosis. There were low but significant correlations between individual values of total WBC and total Osm during exercise (r(sub 0.001(2),284) = 0.39) and during rest plus exercise (r(sub 0.001(2),499) = 0.43). With combined data from the six experiments, mean Osm correlated highly and significantly with both mean WBC (r(sub 0.001(2),6) = 0.95, p < 0.001) and mean platelets (r(sub 0.001(2),6) = 0.94, p < 0.01) during the exercise phase. These data indicate that increases in leucocytes, thrombocytes, and osmolality occur primarily within the first 10 min of high-intensity exercise, but neither hypovolemia nor hyperthermia during exercise contributed to the leucocytosis, thrombocytosis, or hyperosmolality. The high correlations between plasma Osm and WBC or platelet counts suggest changes in osmolality may contribute to the mechanism of leucocytosis and thrombocytosis induced by exercise.

McKenzie, M. A.↗

Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans

The effects of lower body and abdominal pressure, produced by antigravity suit inflation, on blood pressure, pulse rate, fluid and electrolyte shift, plasma vasopressin and plasma renin activity in humans in upright postures were studied. Five men and two women stood upright for 3 hr with the suit being either inflated or uninflated. In the control tests, the suit was inflated only during the latter part of the trials. Monitoring was carried out with a sphygnomanometer, with sensors for pulse rates, and using a photometer and osmometer to measure blood serum characteristics. The tests confirmed earlier findings that the anti-g suit eliminates increases in plasma renin activity. Also, the headward redistribution of blood obtained in the tests commends the anti-g suit as an alternative to water immersion or bed rest for initial weightlessness studies.

Kravik, S. E.↗

Cardiopulmonary Changes with Moderate Decompression in Rats

Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

Robinson, R.↗

Hematology and immunology studies - The second manned Skylab mission

The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.

Kimzey, S. L.↗