PubMed Health⌕ Search

Biomedical subjects

J Vernikos

Publications and source records attributed to J Vernikos.

At least 19 recordsLinked to original sources
PubMed2001

Blood pressure changes during orthostatic stress: evidence of gender differences in neuroeffector distribution.

BACKGROUND: Research has demonstrated that exogenous adrenergic agonists produce dose-related vasoconstriction in men but not women. This suggests that the distribution of adrenergic receptor sites differ with gender. Women may have a higher density of receptor sites in the arterioles (fast acting with low gain) while men may have higher density in the larger vessels (slow acting with high gain). METHODS: To partially test this hypothesis, the time course in beat-to-beat responses in systolic and diastolic BP, and heart rate was compared between six men and six women during the transition from a supine to an upright posture and during prolonged standing. RESULTS: The transient change in systolic and diastolic BP was very rapid in women, but completed within 15 to 30 s after assuming an upright position. Men increased BP at a much slower rate, but continued to produce higher BPs over the complete testing session (up to 15 min). The rate of change for men (15 mm Hg systolic and 10 mm Hg diastolic) was approximately half that for women (30 mm Hg systolic and 15 mm Hg diastolic) during the first 30 s of upright posture. However, after 60 s of standing, absolute change in systolic BP for the men exceeded that of the women by approximately 5 mm Hg for both systolic and diastolic BP. While men's heart rate remained relatively constant during standing, women compensated for the lower change in BP by a continual increase in heart rate throughout the duration of the test. Although both men and women demonstrated increases in norepinephrine at 5 and 15 min during standing, no difference between genders was observed. Similarly, there were no differences in dominant periodicity of heart rate during standing, although women demonstrated slightly higher beat-to-beat variation (RMS) than men. CONCLUSION: The results support the hypothesis of distributional differences in neuroeffector responses between men and women and have implications for how men and women respond to orthostatic stress across a variety of environmental conditions.

Adult↗
PubMed2000

Dietary salt and urinary calcium excretion in a human bed rest spaceflight model.

BACKGROUND: Dietary salt is known to increase the excretion of urinary calcium (Ca). To determine the potential role of dietary sodium (Na) on the calciuria associated with a spaceflight simulation model, we evaluated urinary Ca in two groups of bed rest subjects fed either high or low normal amounts of salt. METHODS: We analyzed urinary Ca excretion expressed in terms of creatinine (UCa/Cr), fractional Ca excretion (FECa), and urinary cAMP (UCAMP) as an index of parathyroid function, in the urine of 30-50-yr-old male volunteers for 6 degrees head down tilt bed rest studies. Dietary Na was in the high normal range (190 mmol x d(-1)) in 8 men for 7 d (HiNa), and in the low normal range (114 mmol x d(-1)) in 11 men for 30 d (LoNa) bed rest. Dietary Ca averaged 20 mmol x d(-1) in both studies. RESULTS: Within the first 3 bed rest days, subjects in the HiNa study showed increases in UCa/Cr (0.1130 +/- 0.05 to 0.161 +/- 0.05, p < 0.002) and in FECa (1.95 +/- 0.70 to 3.19 +/- 0.93, p < 0.001); those in LoNa showed no change in UCa/Cr (0.125 +/- 0.06 to 0.121 +/- 0.07, NS) or FECa (1.93 +/- 0.75 to 2.22 +/- 0.63). After the 5th bed rest day UCa/Cr stabilized at similar levels in both dietary groups. UCAMP decreased 20% during the first week of bed rest with HiNa, but not until the third week with LoNa diets (p < 0.05). CONCLUSION: These findings implicate high salt diets in Ca excretion in a spaceflight model and suggest that low normal salt diets may reduce early calciuria associated with spaceflight.

Adult↗
PubMed1999

Physiological changes in spaceflight that may affect drug action.

Despite nearly 40 years of spaceflight, the paucity of time spent in microgravity and somewhat scattered approach to the study to pharmacology in microgravity have resulted in little solid information. Moreover, they have generally only been studied in the first few days of spaceflight or its simulation by bedrest, when physiological changes are most dynamic. Nevertheless, early physiological responses to microgravity have been well documented and provide good support for the hypothesis that both pharmacokinetics and pharmacodynamics should be altered, with more significant changes occurring as stays in space increase in duration. Whether given orally, by intravenous (IV) or intramuscular (IM) injection, intranasally (IN) or rectally, a drug must distribute through the body, usually crossing certain membranes and becoming bound to other molecules, reach its receptor and bind to it in order to exert its action. This paper, then, will follow a drug's passage through the body in terms of pharmacokinetic parameters known to be affected by microgravity, and mention other factors.

Adaptation, Physiological↗
PubMed1998

Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin.

We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

Adult↗
PubMed1998

The International Space Life Sciences Working Group.

The International Space Life Sciences Working Group (ISLSWG) is made up of representatives from five space agencies: the National Aeronautics and Space Administration (NASA), the European Space Agency (ESA), the Canadian Space Agency (CSA), the Centre National d'Etudes Spatiale (CNES), the Deutsches Zentrum fur Luft- und Raumfahrt (DLR, formerly the Deutsche Agentur fur Raumfahrtangelegenheiten or DARA), and the National Space Development Agency of Japan (NASDA). The group met for the first time in 1989, and since that time has developed a Strategic Plan and has taken concrete steps to implement this plan. The result is a closely coordinated international program of Space Life Sciences which will enable optimal utilization of space flight opportunities.

Biological Science Disciplines↗
PubMed1996

Human physiology in space.

The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

Astronauts↗
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

Catecholaminergic effects of prolonged head-down bed rest.

Prolonged head-down bed rest (HDBR) provides a model for examining responses to chronic weightlessness in humans. Eight healthy volunteers underwent HDBR for 2 wk. Antecubital venous blood was sampled for plasma levels of catechols [norepinephrine (NE), epinephrine, dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid] after supine rest on a control (C) day and after 4 h and 7 and 14 days of HDBR. Urine was collected after 2 h of supine rest during day C, 2 h before HDBR, and during the intervals 1-4, 4-24, 144-168 (day 7), and 312-336 h (day 14) of HDBR. All subjects had decreased plasma and blood volumes (mean 16%), atriopeptin levels (31%), and peripheral venous pressure (26%) after HDBR. NE excretion on day 14 of HDBR was decreased by 35% from that on day C, without further trends as HDBR continued, whereas plasma levels were only variably and nonsignificantly decreased. Excretion rates of dihydroxyphenylglycol and dihydroxyphenylalanine decreased slightly during HDBR; excretion rates of epinephrine, dopamine, and dihydroxyphenylacetic acid and plasma levels of catechols were unchanged. The results suggest that HDBR produces sustained inhibition of sympathoneural release, turnover, and synthesis of NE without affecting adrenomedullary secretion or renal dopamine production. Concurrent hypovolemia probably interferes with detection of sympathoinhibition by plasma levels of NE and other catechols in this setting. Sympathoinhibition, despite decreased blood volume, may help to explain orthostatic intolerance in astronauts returning from spaceflights.

Adult↗
PubMed1994

A sensitive radioimmunoassay for fludrocortisone in human plasma.

Fludrocortisone has been a mainstay of therapy for orthostatic hypotension for many years. Clinical experience suggests that there exists a substantial interindividual variation in responsiveness to the drug. To assess this, we have developed an assay that permits measurement of the low concentrations of fludrocortisone found in human plasma. Fludrocortisone was detected by radioimmunoassay. A polyclonal rabbit antibody, raised against dexamethasone which cross-reacts strongly with fludrocortisone, was reacted with either standard or unknown samples in the presence of [125I]fludrocortisone-3-TyrNH2 (synthesized by coupling tyrosine amide to fludrocortisone-3-oxime and iodinating with chloramine T oxidation). The ED10, ED50, and ED80 were 0.34, 5.0, and 30 ng/mL of plasma, respectively. The cross reactivity with other 9-fluorinated steroids was found as follows: dexamethasone, 340%; betamethasone, 230%; and triamicinolone, 8%. To preclude an erroneous result, subjects who were pregnant or receiving any steroid medication were excluded from the study. The percent cross-reactivity with the main naturally occurring steroids was as follows: 11-desoxycortisol 3.2%, cortisol 1.1%, DOC 0.3%, pregnenolone 0.1%, corticosterone 0.06%, progesterone 0.05%, and aldosterone < 0.05%. The only compound with potential for interference, because of its high level in the circulation in the early morning, was cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Fludrocortisone↗
PubMed1994

Advantages and disadvantages of fludrocortisone or saline load in preventing post-spaceflight orthostatic hypotension.

The purpose of this study was to compare the effectiveness of saline load to fludrocortisone (florinef) as countermeasures for reduced plasma volume and orthostatic intolerance after spaceflight. Eleven males (ages 30-50 yr) underwent a 3-day ambulatory baseline period followed by 7 days of 6 degrees head-down bedrest, during which cardiopulmonary and arterial baroreflex sensitivity and plasma volume (PV) were determined. During pre-bedrest and 2.5 h after treatment on day 8, PV was also measured and subjects underwent a 15-min unsupported stand test. Treatments consisted of 8 salt tablets (1 g NaCl per tablet) and 960 ml of water in 5 subjects and 0.6 mg (0.2 mg x 3) over 24 h in the other 6 subjects. PV decreased by 12% on day 7 of bedrest. This was restored on day 8 by florinef but not by saline load. The effect of florinef on PV was paralleled by decreases in urine volume and the urinary sodium/potassium ratio. Reduced PV was associated with greater vascular resistance for the same drop in central venous pressure, suggesting less vasoconstriction reserve after bedrest. Carotid baroreflex control of heart rate was attenuated after 7 days of bedrest. Both baroreflex functions were restored by florinef but not saline load. Only 1 of 6 subjects showed syncopal symptoms in the florinef-treated group, whereas 4 of 5 subjects did so in the saline-load group. Acute florinef treatment appears to have distinct advantages as a protective measure for post-bedrest orthostatic intolerance, not only through its salt retaining, volume-expanding mineralcorticoid effect, but possibly through its actions on baroreflex and sympathetic functions.

Administration, Oral↗
PubMed1994

The sympathetic nervous system and the physiologic consequences of spaceflight: a hypothesis.

Many of the physiologic consequences of weightlessness and the cardiovascular abnormalities on return from space could be due, at least in part, to alterations in the regulation of the autonomic nervous system. In this article, the authors review the rationale and evidence for an autonomic mediation of diverse changes that occur with spaceflight, including the anemia and hypovolemia of weightlessness and the tachycardia and orthostatic intolerance on return from space. This hypothesis is supported by studies of two groups of persons known to have low catecholamine levels: persons subjected to prolonged bedrest and persons with syndromes characterized by low circulating catecholamines (Bradbury-Eggleston syndrome and dopamine beta-hydroxylase deficiency). Both groups exhibit the symptoms mentioned. The increasing evidence that autonomic mechanisms underlie many of the physiologic consequences of weightlessness suggests that new pharmacologic approaches (such as administration of beta-blockers and/or sympathomimetic amines) based on these findings may attenuate these unwanted effects.

Anemia↗
PubMed1994

Effect of simulated microgravity on cardiopulmonary baroreflex control of forearm vascular resistance.

The stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR) were studied in 11 healthy men before and after 7 days of 6 degrees head-down bedrest to test the hypothesis that microgravity alters this reflex response. We assessed the relationship between stimulus [changes in central venous pressure (delta CVP)] and reflex response (delta FVR) during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP; 0 to -20 mmHg). delta CVP during bedrest and LBNP was estimated from peripheral vein pressures in the dependent right arm. Compared with prebedrest baseline, plasma volume and estimated CVP were decreased by 13 and 33%, respectively, at 7 days of bedrest. Progressive reflex forearm vasoconstriction occurred in response to graded reductions in estimated CVP during LBNP, and delta FVR per unit delta CVP was doubled after bedrest. The increase in sensitivity of the cardiopulmonary baroreflex control of FVR was related to reduced circulating blood volume, suggesting that enhanced peripheral vasoconstriction in individuals adapted to microgravity can be attributed, in part, to hypovolemia. In addition, microgravity appears to alter the stimulus for cardiopulmonary baroreceptors to a lower operational range of CVP, suggesting the possibility of chronic resetting.

Adult↗
PubMed1994

Altered baroreflex control of forearm vascular resistance during simulated microgravity.

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

Adult↗
PubMed1993

Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest.

Endocrine regulation of fluids and electrolytes during 7 days of -6 degrees head-down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 h before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na(+)-to-K+ ratio and significant Na+ retention on re-ambulation. After the 1st day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone (Aldo), plasma volume was decreased, and the renal response to Aldo appeared to be appropriate. Circulating levels of arginine vasopressin, cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of early morning ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 days of HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after HDBR revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing before and after HDBR. Females had greater PRA and Aldo responses to standing before HDBR and larger Aldo responses to standing after HDBR than males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of leg exercise training on vascular volumes during 30 days of 6 degrees head-down bed rest.

Plasma and red cell volumes, body density, and water balance were measured in 19 men (32-42 yr) confined to bed rest (BR). One group (n = 5) had no exercise training (NOE), another near-maximal variable-intensity isotonic exercise for 60 min/day (ITE; n = 7), and the third near-maximal intermittent isokinetic exercise for 60 min/day (IKE; n = 7). Caloric intake was 2,678-2,840 kcal/day; mean body weight (n = 19) decreased by 0.58 +/- 0.35 (SE) kg during BR due to a negative fluid balance (diuresis) on day 1. Mean energy costs for the NOE, and IKE, and ITE regimens were 83 (3.6 +/- 0.2 ml O2.min-1.kg-1), 214 (8.9 +/- 0.5 ml.min-1.kg-1), and 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1), respectively. Body densities within groups and mean urine volumes (1,752-1,846 ml/day) between groups were unchanged during BR. Resting changes in plasma volume (ml/kg) after BR were -1.5 +/- 2.3% (NS) in ITE, -14.7 +/- 2.8% (P less than 0.05) in NOE, and -16.8 +/- 2.9% (P less than 0.05) in IKE, and mean water balances during BR were +295, -106, and +169 ml/24 h, respectively. Changes in red cell volume followed changes in plasma volume. The significant chronic decreases in plasma volume in the IKE and NOE groups and its maintenance in the ITE group could not be accounted for by water balance or by responses of the plasma osmotic, protein, vasopressin, or aldosterone concentrations or plasma renin activity. There was close coupling between resting plasma volume and plasma protein and osmotic content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Drug effects on orthostatic intolerance induced by bedrest.

Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma volume (PV), dextroamphetamine (Dex) to enhance norepinephrine (NE) release and atropine (A) to reduce the effects of vagal stimulation. Seven subjects with proven post-bedrest orthostatic intolerance returned for a 7-day 6 degrees head-down bedrest study. F (0.2 mg) was given at 8:00 AM and 8:00 PM the day before and 8:00 AM the day the subjects got out of bed (2 hours before standing). PV was measured before and 1 hour after the last dose of F. D (5 mg) and A (0.8 mg) were then taken orally 1 hour before the stand test. F expanded PV by 16% and caused sodium retention. Four of the 7 subjects stood for 1 hour post-bedrest and HR, plasma NE and PRA responses to standing were greatly enhanced and sustained. Although there was a narrowing of pulse pressure, the ability to overcome orthostatic intolerance with these countermeasures was largely due to vasoconstriction and sustained high heart rate. The existing literature on pharmacologic countermeasures for post-flight and post-bedrest orthostatic hypotension is reviewed, and the results are discussed in that context.

Adult↗
PubMed1982

Pituitary-adrenal function in rats chronically exposed to cold.

Exposure to cold for 2 weeks was used to assess the effects of a sustained stimulus on pituitary-adrenal function in male rats. The diurnal peak in plasma and adrenal corticosterone was advanced by 4 h during the first 24 h of exposure to cold but returned to its usual time (2000 h) by the next day. Plasma ACTH and corticosterone levels were generally greater at all times during the 24-h cycle in animals exposed to cold for up to 2 weeks, with the greatest increase occurring consistently at the time of peak. When rats exposed to cold for 1 week were returned to a normal 24 C environment, plasma corticosterone tended to increase. Plasma ACTH and plasma and adrenal corticosterone responses to a superimposed acute provocative stimulus (ip saline injection) were faster, greater, and more sustained in rats exposed to cold for 3 or 7 days. Similarly, the compensatory adrenal hypertrophy response to unilateral adrenalectomy was greater in cold-exposed rats. Such animals were also more resistant to pituitary-adrenal suppression by prednisolone. In contrast, there was no change in the sensitivity of the adrenal to exogenous ACTH. The results suggest that chronic exposure to cold causes a sustained activation of central mechanisms that regulate pituitary ACTH secretion as well as extra-pituitary mechanisms that regulate adrenal size; it reduces the effectiveness of negative feedback mechanisms, but does not alter those involved in the regulation of adrenal rhythmicity or adrenal sensitivity to ACTH.

Adrenal Glands↗