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Biomedical subjects

C E Wade

Publications and source records attributed to C E Wade.

At least 55 records · Page 3Linked to original sources
PubMed1998

Alteration of renal function of rats following spaceflight.

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

Animals↗
PubMed1998

Size constraints of telemeters in rats.

This study was designed to determine the maximum-size subcutaneous telemeter that would enable long-term and multichannel data collection in a 170-g rat for 90 days. In phase 1, rats with implants weighing 5 (2.5 cm3), 15 (7.5 cm3), 25 (12.5 cm3), 35 (17.5 cm3), or 45 (22.5 cm3) g were compared with sham-operated (SOC) and nonoperated (NOC) control animals. Severe skin lesions, seromas, and lower growth rates were observed in rats having implants >/=35 g. Thus, in phase 2, rats implanted with 23.5 g (17.5 cm3; 11-g active telemeter and 12.5-g implant) were compared with rats implanted with 11 g (6 cm3; telemeter only) and with the SOC and NOC groups. No differences were found among implanted groups in mean arterial pressure (MAP), heart rate (HR), subcutaneous temperature, or spontaneous activity under standard housing conditions. All groups were more active and had a higher MAP during the dark than the light phase of the daily cycle. During 2 h of cold exposure (3 degreesC), both telemetered groups exhibited similar changes in HR, MAP, temperature, and activity levels. Adrenal glands were larger in the 23.5-g group (51 +/- 1.6 mg) than in the SOC (46 +/- 1.0 mg) and the NOC groups (41 +/- 2.0 mg). No other significant differences were found in organ, muscle, or bone weights. These data verify the feasibility of using 23.5-g (17.5 cm3) subcutaneous telemeters for chronic recordings in young adult rats.

Animals↗
PubMed1998

Comparison of hyper- and microgravity on rat muscle, organ weights and selected plasma constituents.

BACKGROUND: Centrifugation has been proposed to be one possible countermeasure for the skeletal muscle, organ, hormonal, and plasma chemistry adaptations associated with chronic unloading (e.g., during spaceflight). HYPOTHESIS: Our hypothesis was that there would be a continuum of physiological and morphological responses from zero gravity to hypergravity. METHODS: Adult male rats were centrifuged continuously at 2G for 14 d and the weights of limb muscles and organs, and the levels of plasma constituents were compared with the same measurements from rats flown on a 14-d spaceflight (Cosmos 2044). RESULTS: Mean body weights of centrifuge rats did not change, whereas age-matched controls grew 21%. There was a sparing of muscle protein in the centrifuge rats; the absolute weights of predominantly slow muscles in the hindlimb were maintained and the relative weights (expressed relative to body weight and as a percent difference from control) of almost all muscles studied were larger than control. In contrast, spaceflight resulted in a decrease in the relative weights of most extensor, but not flexor, hindlimb muscles studied. Relative organ weights, in general, were elevated in centrifuge rats compared with control rats. Relative organ weights in flight rats were similar to control, except for a decrease in testes weight. Plasma thyroxine and testosterone levels were significantly reduced following flight, whereas only thyroxine was decreased after centrifugation. Centrifugation resulted in a decrease in most other plasma chemistry measurements, whereas flight rats showed no change or an elevation in these measures. DISCUSSION: These data indicate that the physiological responses to micro- and hypergravity are often in the opposite direction, suggesting that in general there is a continuum of physiological and morphological effects from microgravity to 1G to hypergravity. These data further suggest that the imposition of hypergravity conditions on animals that are in a microgravity environment may have a beneficial effect in maintaining some physiological systems at or near control levels.

Animals↗
PubMed1998

Reduction of pituitary AVP and OT contents in rats following spaceflight.

BACKGROUND: Responses of pituitary concentrations of vasopressin (AVP) and oxytocin (OT) during spaceflight have been variable, possibly due to differences in flight conditions or in age and strain of flight animals. METHODS: We reviewed findings of three space-flights of varying flight and recovery durations in which rats of different ages and strains were used. Male rats ranging in weight from 248-396 g were flown in space for 7-14 d. Flight animals were then compared with vivarium controls and synchronous controls. Parallel ground-based studies (hypergravity and simulated hypogravity) were conducted. RESULTS: Pituitary content of AVP was significantly (p < or = 0.05) decreased by spaceflight (6.3 +/- 0.3 micrograms.mg-1 protein in flight vs. 8.3 +/- 0.5 micrograms.mg-1 protein in vivarium). OT content was also reduced during spaceflight (4.3 +/- 0.2 micrograms.mg-1 protein in flight vs. 6.1 +/- 0.3 micrograms.mg-1 protein in vivarium). Vivarium and synchronous control rats showed no difference in pituitary contents. Flight duration or recovery times did not appear to influence pituitary hormone contents. Strain of rat had an effect on content but not on responses to spaceflight. Age of animals confounded the response to spaceflight: pituitary contents of AVP and OT were not altered in young animals (< or = 60 d old). Hindlimb suspended animals showed no difference in AVP but OT content was decreased. Ground-based exposure to hypergravity (2 G) did not alter content of AVP or OT in young animals. CONCLUSIONS: Decreases in pituitary content of AVP and OT with spaceflight may be due to a variety of factors unique to the microgravity environment. Differences between studies may be due in part to differences in size and age of rats used.

Age Factors↗
PubMed1997

Efficacy of hypertonic 7.5% saline and 6% dextran-70 in treating trauma: a meta-analysis of controlled clinical studies.

BACKGROUND: Individual trials of small-volume resuscitation of 7.5% NaCl (HS) with and without 6% dextran 70 (HSD) for the treatment of trauma have failed to provide convincing evidence of efficacy. We performed a meta-analysis to evaluate the effects of HS and HSD on survival until discharge or for 30 days. We identified eight double-blinded, randomized controlled trials of HSD and six trials of HS. In all cases, administration of 250 ml of HSD or HS was compared with a control group administration of 250 ml of isotonic crystalloid for the treatment of hypotension either in the field or at admission to the emergency department. METHODS: A fixed-effects meta-analysis was performed with the Mantel-Haenszel method of combining results from multiple studies. RESULTS: Overall, HS was not effective in improving survival with a weighted mean difference in survival of the HS group versus the isotonic control group equal to 0.6%. The results with HSD were more positive, with an increase in survival in seven of eight trials. The mean difference in survival rates favoring HSD (n = 615) over controls (n = 618) was 3.5% (p = 0.14, two-tailed; p = 0.07, one-tailed). The odds ratio was estimated to be 1.20 in favor of HSD with a 95% confidence interval of 0.94 to 1.57. CONCLUSIONS: The meta-analysis of the available data shows that HS is not different from the standard of care and that HSD may be superior.

Controlled Clinical Trials as Topic↗
PubMed1997

Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension.

BACKGROUND: Resuscitation with hypertonic saline/dextran (HSD) has been suggested to be efficacious in patients who have traumatic brain injury and are hypotensive. We undertook a cohort analysis of individual patient data from previous prospective randomized double-blinded trials to evaluate improvements in survival at 24 hours and discharge after initial treatment with HSD in patients who had traumatic brain injury (head region Abbreviated Injury Score > or = 4) and hypotension (systolic blood pressure < or = 90 mm Hg). METHODS: All variables and end points were defined before initiation of data handling. Investigators were blind as to the treatment. Case report forms were received from six studies. Of these, 223 patients met the inclusion for traumatic brain injury. Comparisons between HSD and standard of care were made using stratified analysis and logistic regression to assess efficacy, confounding, and interaction. Potential confounding variables of pre-fluid treatment, Glasgow Coma Scale score (3-8 vs. 9-15), injury type, and systolic blood pressure can be considered a priori factors that were known before randomization. Effects of the various trials was also considered. RESULTS: Treatment with HSD resulted in a survival until discharge of 37.9% (39 of 103) compared with 26.9% (32 of 119) with standard of care (p = 0.080). Using logistic regression, adjusting for trial and potential confounding variables, the treatment effect can be summarized by the odds ratio of 2.12 (p = 0.048) for survival until discharge. CONCLUSIONS: Patients who have traumatic brain injuries in the presence of hypotension and receive HSD are about twice as likely to survive as those who receive standard of care.

Abbreviated Injury Scale↗
PubMed1997

Space Station Biological Research Project.

To meet NASA's objective of using the unique aspects of the space environment to expand fundamental knowledge in the biological sciences, the Space Station Biological Research Project at Ames Research Center is developing, or providing oversight, for two major suites of hardware which will be installed on the International Space Station (ISS). The first, the Gravitational Biology Facility, consists of Habitats to support plants, rodents, cells, aquatic specimens, avian and reptilian eggs, and insects and the Habitat Holding Rack in which to house them at microgravity; the second, the Centrifuge Facility, consists of a 2.5 m diameter centrifuge that will provide acceleration levels between 0.01 g and 2.0 g and a Life Sciences Glovebox. These two facilities will support the conduct of experiments to: 1) investigate the effect of microgravity on living systems; 2) what level of gravity is required to maintain normal form and function, and 3) study the use of artificial gravity as a countermeasure to the deleterious effects of microgravity observed in the crew. Upon completion, the ISS will have three complementary laboratory modules provided by NASA, the European Space Agency and the Japanese space agency, NASDA. Use of all facilities in each of the modules will be available to investigators from participating space agencies. With the advent of the ISS, space-based gravitational biology research will transition from 10-16 day short-duration Space Shuttle flights to 90-day-or-longer ISS increments.

Aerospace Medicine↗
PubMed1997

Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint.

Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

Animals↗
PubMed1997

Body mass change during altered gravity: spaceflight, centrifugation, and return to 1 G.

To assess the effect of gravity on growth, immature rats (130-200 g) were studied during chronic altered gravity exposure and while transitioning between gravity fields. Body mass gain of rats (n = 12) exposed to 14 days of microgravity (spaceflight) was evaluated and compared to mass gain of 1 G controls. Spaceflight did not affect mass gain. Six rats exposed to 1 G following spaceflight, when compared to controls, experienced a significant (0 < 0.05) post-flight mass loss over 48 h of 13 g. Over subsequent days, however, this loss was compensated for, and no difference from 1 G controls was noted after 5 days. Exposure to hypergravity (2 G) for 16 days was evaluated [(n = 6/group): Centrifuge (C); On Center Control (OCC); Centrifuge Control (CC)]. Body mass of centrifuged and OCC rats was reduced within 24 h, with OCCs regaining control mass within 13 days. The mass difference (44 g) in centrifuged animals persisted, however, with no subsequent difference in rate of mass gain between centrifuged animals and controls over Days 3-16 (3.7 +/- 0.1 vs. 3.9 +/- 0.1 g/day, respectively). Transitioning from 2 G to 1 G resulted in a mass increase within 48 hours for centrifuged animals. Over Days 3-16 at 1 G, the rate of gain for centrifuged animals continued to increase (3.1 +/- 0.1 g/day compared to 2.1 +/- 0.1 g/day for controls); differences from control, however, were still noted on Day 16. Transitioning to an increase in a gravity field causes acute losses in body mass. In hypergravity, the acute reduction in body mass persists but the rate of mass gain is normal. Animals returning to 1 G, after acute changes, adjust to attain control mass.

Adaptation, Physiological↗
PubMed1996

The renal effects of 7.5% NaCl-6% dextran-70 versus lactated Ringer's resuscitation of hemorrhage in dehydrated sheep.

A small volume of 7.5% NaCl/6% Dextran-70 (HSD) can rapidly expand the plasma volume, but concerns exist regarding its adverse effects on renal function in the dehydrated state. Sheep were thirsted for 4 days (13% plasma volume contraction), and subjected to a fixed-pressure shock model (mean arterial pressure of 50 mmHg for 2 h), followed by resuscitation with either HSD (4 mL/kg) or lactated Ringer's solution (LR; 37 mL/kg). Mean arterial pressure was restored to 90%, cardiac output to 125% and 120%, and plasma volume to 78% and 72% of baseline in LR and HSD groups, respectively. Glomerular filtration rate improved to 100% of baseline following HSD compared with 82% following LR. No significant urinary 70,000 molecular weight dextran was observed, suggesting an intact renal glomerular membrane. These data suggest that small volume HSD resuscitation is effective, even with pre-existing dehydration. In addition, renal function is not compromised by HSD resuscitation of hemorrhaged, dehydrated animals.

Animals↗
PubMed1996

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

BACKGROUND/HYPOTHESIS: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used. METHODS: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz). RESULTS: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4. CONCLUSIONS: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.

Adult↗
PubMed1995

Effects of chronic elevated levels of CO2 on the concentration of blood cellular elements and plasma corticosterone in the male rat.

The mean CO2 concentration on the Space Shuttle is 0.3% and has reached 0.7%, for extended periods of time. Following space flight, it has been shown that both humans and animals have significant changes in red blood cell counts (RBC) and white blood cell counts (WBC). In other studies, where no difference occurred in total WBC, a significant change did occur in the distribution of WBC. WBC are affected by circulating levels of glucocorticoids, which often increase when animals or humans are exposed to adverse and/or novel stimuli (e.g. elevated CO2 levels or weightlessness). The purpose of this study was to determine if elevations in CO2 concentration produce changes in total WBC and/or their distribution.

Animals↗
PubMed1995

Dose response effects of hypertonic saline and dextran on cardiovascular responses and plasma volume expansion in sheep.

Despite the established efficacy of 7.5% NaCl/6% dextran-70 in the treatment of hypovolemia, the optimal formulation of a hyperosmotic/hyperoncotic small volume resuscitation solution has yet to be defined. The present study investigates the cardiovascular effects of hypertonic saline ranging from 3.75%-25% NaCl (HS) and dextran-70 (D-70) ranging from 3 to 24%. HS and D-70 were studied alone or in specific combinations at a dose of 4 mL/kg, in euvolemic sheep. Blood samples were collected before, during and up to 60 min after infusion of the test solutions. Dose-dependent effects of HS were immediate increases in cardiac output (CO) of 30-85%, falling to 10-35% over baseline after 60 min. HS concentrations over 3.75% significantly reduced systemic vascular resistance, but HS had no significant effect on mean arterial pressure (MAP). Plasma volume (PV) expansion with HS was an immediate, but transient increase of 12-35%. Infusion of D-70 induced sustained 10-20% increases in CO and 10-30% increases in PV, peaking 10 min post-infusion. D-70 also resulted in small (5-12 mmHg) increases in MAP. Cardiovascular effects of D-70 correlated with a dose-dependent increase in plasma dextran concentrations. All HS solutions significantly increased plasma Na, which peaked at > or = 200 mEq/L in the 25% group. The effects of D-70 and HS combined were additive on PV expansion and CO. These data indicate that concentrations of HS and D-70 which are higher than those currently used have a greater capability for expanding PV, but use of HS > 7.5% may be limited by resulting hypernatremia.

Animals↗
PubMed1994

A review of the efficacy and safety of 7.5% NaCl/6% dextran 70 in experimental animals and in humans.

Recent years have seen a renewed interest in the use of hypertonic-hyperoncotic solutions as plasma volume expanders for the treatment of hemorrhagic hypotension. In particular, a number of studies in experimental animals have addressed the efficacy and safety of small-volume infusions of 7.5% NaCl/6% dextran 70 (HSD). Employing models of fixed volume or fixed pressure hemorrhage, HSD has improved survival and reversed many of the hemodynamic, hormonal, and metabolic abnormalities associated with hemorrhagic shock. In the few human field trials completed to date, HSD has been shown to be potentially beneficial in hypotensive trauma patients who require surgery or have concomitant head injury. Extensive toxicologic evaluations and lack of reports of adverse effects in the human trials indicate that, at the proposed therapeutic dose of 4 mL/kg, HSD should present little risk.

Animals↗
PubMed1993

Lactated Ringer's solution alleviates brain trauma-precipitated lactic acidosis in hemorrhagic shock.

To determine the influence of brain trauma on blood acid-base and lactate-pyruvate responses to hemorrhage, and the effect of lactated Ringer's solution on these responses, 30 anesthetized rats were assigned to four groups: hemorrhage (n = 7), hemorrhage following fluid percussion brain trauma (trauma-hemorrhage group) (n = 7), hemorrhage treated with lactated Ringer's solution (hemorrhage-resuscitation group) (n = 8), and hemorrhage following brain trauma treated with lactated Ringer's solution (trauma-hemorrhage-resuscitation group) (n = 8). The hemorrhage group showed no significant changes in pH, HCO3, and base excess after hemorrhage. Base excess and pH were significantly reduced after the hemorrhage in the trauma-hemorrhage group but were raised after resuscitation in the hemorrhage-resuscitation group. Acid-base values showed no difference between the trauma-hemorrhage-resuscitation and hemorrhage groups. The trauma-hemorrhage-resuscitation group also had a significantly higher base excess than the trauma-hemorrhage group. Lactate rose significantly after hemorrhage in the hemorrhage group and was even higher in the trauma-hemorrhage group, but there were no differences between the hemorrhage versus hemorrhage-resuscitation or trauma-hemorrhage-resuscitation groups. Both brain trauma and lactated Ringer's solution increased pyruvate with marked reduction in the ratio of lactate to pyruvate. These data indicate that brain trauma precipitates blood lactate accumulation and metabolic acidosis after hemorrhage, and infusion of lactated Ringer's solution can relieve these disturbances.

Acidosis, Lactic↗
PubMed1993

The divergent effect of RU 486 on adrenal function in the dog is related to differences in its pharmacokinetics.

This study has evaluated the relationship between the antiglucocorticoid effect of RU 486 and its pharmacokinetics in seven female mongrel dogs (weight 21-30 kg), all of which had appropriate responses to insulin-induced hypoglycemia and metyrapone. They were given RU 486 (50 mg.kg-1.d-1) for ten days. Three dogs (responders) demonstrated increased secretion of ACTH and cortisol which reached a maximum at the termination of RU 486 administration and returned to baseline by days 22 and 18, respectively. The remaining four dogs (non-responders) showed only transient non-sustained increases in ACTH and cortisol. Serum concentrations of RU 486 and its monodemethylated and di-demethylated (but not its hydroxylated) metabolites were significantly higher in the responder dogs. The ratios of the hydroxylated metabolite to RU 486 and its demethylated derivatives were higher in the non-responders, whereas the ratio of the di-demethylated to monodemethylated compound was higher in the responders. Since variations in the hydroxylation and reductive catabolism of steroids have been well documented in different strains of a species, it is possible that the differences in levels of RU 486 and its metabolites in the two groups are accounted for by variations in RU 486 metabolism. In the responder group the metabolism of RU 486 is directed to demethylation, and in the non-responder group to hydroxylation. Thus, differences in pharmacokinetics of RU 486 in the two groups of dogs may explain the variable biological response to this antiglucocorticoid.

Administration, Oral↗
PubMed1993

Comparison of hypertonic saline solutions and dextran in dialysis-induced hypotension.

The efficacy of three hypertonic saline solutions for treating dialysis-induced hypotension in a randomized, blinded, crossover clinical trial of 10 patients (a minimum of three cycles per solution) was compared. Dialysis-induced hypotension, defined as a decrease in systolic blood pressure of at least 10 mm Hg or systolic blood pressure less than 100 mm Hg, was treated with an iv bolus of either 10 mL of 23% saturated hypertonic saline, 30 mL of 7.5% hypertonic saline, or 30 mL of 7.5% saline with 6% dextran 70, each containing similar osmolar loads of 80, 80, and 100 mosM, respectively. All three solutions raised systolic blood pressure within 5 min (mean pretreatment systolic blood pressure, 87 mm Hg; mean posttreatment systolic blood pressure, 101 mm Hg; P < 0.05). The magnitude of the increase was greater with saturated hypertonic saline (15 mm Hg) and dextran 70 (17 mm Hg) compared with that with hypertonic saline (9 mm Hg; P < 0.05). At 10 min, dialysis-induced hypotension was less frequent with saturated hypertonic saline (incidence, 9%) compared with hypertonic saline (45%). Beyond 10 min, however, there was a trend toward a lower incidence of further dialysis-induced hypotension with dextran 70. There were no side effects. Given equal osmole loads, the more concentrated solution produced a greater increase in systolic blood pressure. The addition of an oncotic agent such as dextran may prolong the blood pressure response beyond 10 min. It was concluded that hypertonic saline solutions safely and effectively treat dialysis-induced hypotension.

Aged↗