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Janice V Meck

Publications and source records attributed to Janice V Meck.

17 recordsLinked to original sources
PubMed2006

Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance.

Microgravity (microG)-induced orthostatic intolerance (OI) in astronauts is characterized by a marked decrease in cardiac output (CO) in response to an orthostatic stress. Since CO is highly dependent on venous return, alterations in the resistance to venous return (RVR) may be important in contributing to OI. The RVR is directly dependent on arterial compliance (C(a)), where aortic compliance (C(ao)) contributes up to 60% of C(a). We tested the hypothesis that microG-induced changes in C(a) may represent a protective mechanism against OI. A retrospective analysis on hemodynamic data collected from astronauts after 5- to 18-day spaceflight missions revealed that orthostatically tolerant (OT) astronauts showed a significant decrease in C(a) after spaceflight, while OI astronauts showed a slight increase in C(a). A ground-based animal model simulating microG, hindlimb-unweighted rats, was used to explore this phenomenon. Two independent assessments of C(ao), in vivo pulse wave velocity (PWV) of the thoracic aorta and in vitro pressure-diameter squared relationship (PDSR) measurements of the excised thoracic aorta, were determined. PWV showed a significant increase in aortic stiffness compared with control, despite unchanged blood pressures. This increase in aortic stiffness was confirmed by the PDSR analysis. Thus both actual microG in humans and simulated microG in rats induces changes in C(ao). The difference in C(a) in OT and OI astronaut suggests that the microG-induced decrease in C(a) is a protective adaptation to spaceflight that reduces the RVR and allows for the maintenance of adequate CO in response to an orthostatic stress.

Adaptation, Physiological↗
PubMed2006

Computer systems analysis of spaceflight induced changes in left ventricular mass.

Circulatory adaptations resulting in postflight orthostasis have frequently been observed in response to space travel. It has been postulated that a decrement in left ventricular mass (LVM) found after microgravity exposure may be the central component in this cardiovascular deconditioning. However, a physiologic mechanism responsible for these changes in the myocardium has not been determined. In this study, we examined the sequential alterations in echocardiographic measured LVM from preflight to landing day and 3 days into the postflight recovery period. In a previous study in returning astronauts we found a comparative 9.1% reduction in postflight LVM that returned to preflight values by the third day of recovery. This data was further evaluated in a systems analysis approach using a well-established advanced computer model of circulatory functioning. The computer model incorporates the physiologic responses to changes in pressures, flows and hydraulics within the circulatory system as affected by gravitational forces. Myocardial muscle progression to atrophy or hypertrophy in reaction to the circulatory load conditions is also included in the model. The integrative computer analysis suggests that these variations in LVM could be explained by simple fluid shifts known to occur during spaceflight and can reverse within a few days after reentry into earth's gravity. According to model predictions, the reductions in LVM found upon exposure to microgravity are a result of a contraction of the myocardial interstitial fluid space secondary to a loss in the plasma volume. This hypothesis was additionally supported by the published ground-based study in which we followed the alterations in LVM and plasma volume in normal subjects in which hypovolemia was induced by simple dehydration. In the hypovolemic state, plasma volume was reduced in these subjects and was significantly correlated with echocardiographic measurements of LVM. Based on these experimental findings and the performance of the computer systems analysis it appears that reductions in LVM observed after spaceflight may be secondary to fluid exchanges produced by common physiologic mechanisms. Reductions in LVM observed after microgravity exposure have been previously postulated to be a central component of spaceflight-induced cardiovascular deconditioning. However, a recent study has demonstrated a return of astronauts' LVM to preflight values by the third day after landing through uncertain mechanisms. A systems analysis approach using computer simulation techniques allows for a dissection of the complex physiologic control processes and a more detailed examination of the phenomena. From the simulation studies and computer analysis it appears that microgravity induced reductions in LVM may be explained by considering physiologic fluid exchanges rather than cardiac muscle atrophy.

Adult↗
PubMed2006

Hemodynamic effects of midodrine after spaceflight in astronauts without orthostatic hypotension.

INTRODUCTION: Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The alpha-1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. METHODS: Five male astronauts participated in preflight and post-flight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing approximately 1 h before testing. RESULTS: None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight; in fact, a modest beneficial effect was seen on postflight tachycardia (p = 0.036). DISCUSSION: These data show that midodrine protected against post-spaceflight increases in heart rate without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure.

Adrenergic alpha-Agonists↗
PubMed2005

Mechanism of spaceflight-induced changes in left ventricular mass.

Decrements in left ventricular (LV) mass observed after microgravity exposure have been previously postulated to be a central component of spaceflight-induced cardiovascular deconditioning. In this study, echocardiographic measurements of LV mass in astronauts demonstrated a comparative 9.1% reduction in postflight LV mass that returned to preflight values by the third day of recovery. A ground-based study in normal subjects determined that these pre- to postflight LV mass changes could be reproduced by simple dehydration. Reductions in LV mass observed immediately after spaceflight may be secondary to simple physiologic fluid exchanges.

Adult↗
PubMed2004

Plasma volume restoration with salt tablets and water after bed rest prevents orthostatic hypotension and changes in supine hemodynamic and endocrine variables.

Head-down bed rest changes the values of many cardiovascular and endocrine variables and also elicits significant hypovolemia. Because previous studies had not controlled for hypovolemia, it is unknown whether the reported changes were primary effects of bed rest or secondary effects of bed rest-induced hypovolemia. We hypothesized that restoring plasma volume with salt tablets and water after 12 days of head-down bed rest would result in an absence of hemodynamic and endocrine changes and a reduced incidence of orthostatic hypotension. In 10 men, we measured changes from pre-bed-rest to post-bed-rest in venous and arterial pressures; heart rate; stroke volume; cardiac output; vascular resistance; plasma norepinephrine, epinephrine, vasopressin, renin activity (PRA), and aldosterone responses to different tilt levels (0 degrees, -10 degrees, 20 degrees, 30 degrees, and 70 degrees); and plasma volume and platelet alpha2- and lymphocyte beta2-adrenoreceptor densities and affinities (0 degrees tilt only). Fluid loading at the end of bed rest restored plasma volume and resulted in the absence of post-bed-rest orthostatic hypotension and changes in supine hemodynamic and endocrine variables. Fluid loading did not prevent post-bed-rest increases in beta2-adrenoreceptor density or decreases in the aldosterone-to-PRA ratio (P = 0.05 for each). Heart rate, epinephrine, and PRA responses to upright tilt after bed rest were increased (P < 0.05), despite the fluid load. These results suggest that incidents of orthostatic hypotension and many of the changes in supine hemodynamic and endocrine variables in volume-depleted bed-rested subjects occur secondarily to the hypovolemia. Despite normovolemia after bed rest, beta2-adrenoreceptors were upregulated, and heart rate, epinephrine, and PRA responses to tilt were augmented, indicating that these changes are independent of volume depletion.

Adult↗
PubMed2004

Short-duration spaceflight does not prolong QTc intervals in male astronauts.

Although ventricular dysrhythmias are not increased during, and QTc intervals are not prolonged after, short-duration (5 to 16 days) spaceflights, QTc intervals have not previously been reported during these shorter flights. Holter monitor recordings, obtained in 11 male astronauts who flew on shuttle missions ranging from 5 to 10 days, showed that QTc intervals did not change significantly 10 days before launch, on 2 separate days of spaceflight, and 2 days after landing. Taken together, these data and our previous report show that QTc interval prolongation occurs sometime between the 9th and 30th days of spaceflight.

Adult↗
PubMed2004

Presyncopal/non-presyncopal outcomes of post spaceflight stand tests are consistent from flight to flight.

INTRODUCTION: The overall prevalence of orthostatic hypotension after short duration (6-18 d) spaceflight is 20% with existing countermeasures. However, it is not known if the outcomes of stand tests for orthostatic tolerance are consistent within individuals on subsequent flights, or if first time fliers are more (or less) likely to experience orthostatic hypotension and presyncope than are veteran astronauts. METHODS: There were 50 astronauts who were studied retrospectively. Stand test data, which had been collected before and after spaceflight, were compared from at least two flights for each astronaut. For 25 of these astronauts, their first flight in this database was also their first spaceflight. For the remaining 25, their first flight in this database was their second, third, or fourth flight, as data were available. RESULTS: No subject became presyncopal during preflight testing. Of the 50 subjects, 45 (90%) had the same outcome on their first and second flights of this study. Of 14 subjects on whom we had data from a third mission, 12 had the same stand test outcome on all 3 flights (86% same outcome across 3 flights). There was no correlation between flight duration and orthostatic tolerance (r = 0.39). DISCUSSION: These data support the idea that astronauts are predisposed to orthostatic tolerance/intolerance after spaceflight and that this predisposition is not altered by subsequent flights. Flight durations within this data set did not alter the likelihood of orthostatic intolerance and rookie fliers were no more likely to experience orthostatic intolerance than were veteran astronauts.

Adaptation, Physiological↗
PubMed2004

Fludrocortisone does not prevent orthostatic hypotension in astronauts after spaceflight.

BACKGROUND: During stand/tilt tests after spaceflight, 20% of astronauts experience orthostatic hypotension and presyncope. Spaceflight-induced hypovolemia is a contributing factor. Fludrocortisone, a synthetic mineralocorticoid, has been shown to increase plasma volume and orthostatic tolerance in Earth-bound patients. The efficacy of fludrocortisone as a treatment for postflight hypovolemia and orthostatic hypotension in astronauts has not been studied. Our purpose was to test the hypothesis that astronauts who ingest fludrocortisone prior to landing would have less loss of plasma volume and greater orthostatic tolerance than astronauts who do not ingest fludrocortisone. METHODS: There were 25 male astronauts who were randomized into 2 groups: placebo (n = 18) and fludrocortisone (n = 7), and participated in stand tests 10 d before launch and 2-4 h after landing. Subjects took either 0.3 mg fludrocortisone or placebo orally 7 h prior to landing. Supine plasma and red cell volumes, supine and standing HR, arterial pressure, aortic outflow, and plasma norepinephrine and epinephrine were measured. RESULTS: On landing day, 2 of 18 in the placebo group and 1 of 7 in the fludrocortisone group became presyncopal (chi2 = 0.015, p = 0.90). Plasma volumes were significantly decreased after flight in the placebo group, but not in the fludrocortisone group. During postflight stand tests, standing plasma norepinephrine was significantly less in the fludrocortisone group compared with the placebo group. CONCLUSIONS: Treatment with a single dose of fludrocortisone results in protection of plasma volume but no protection of orthostatic tolerance. Fludrocortisone is not recommended as a countermeasure for spaceflight-induced orthostatic intolerance.

Adult↗
PubMed2004

Midodrine prescribed to improve recurrent post-spaceflight orthostatic hypotension.

Many astronauts exhibit post-spaceflight orthostatic hypotension due to inadequate norepinephrine release when in an upright posture. We hypothesized that an alpha1-adrenergic agonist, midodrine, would be an effective countermeasure. A female astronaut, who had problems with postflight orthostatic hypotension after a previous flight, consumed 10 mg midodrine after a subsequent flight, prior to her tilt test. Hemodynamic variables were compared between the two flights. Midodrine prevented severe falls in stroke volume, cardiac output and systolic pressure, and severe increases in heart rate without increasing vascular resistance, thus preventing orthostatic hypotension. This is the first report showing that midodrine has the potential to improve post-spaceflight orthostatic hypotension and suggesting that reduced venous return contributes to the etiology.

Adrenergic alpha-Agonists↗
PubMed2003

Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight.

Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only approximately 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A (a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1). significantly smaller pressor responses to phenylephrine both before and after flight; 2). significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3). significantly greater norepinephrine release with tyramine on landing day; and 4). significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired.

Adrenergic alpha-Agonists↗
PubMed2003

Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight.

Insomnia is a common symptom, not only in the adult population but also in many astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an imidazopyridine), are often taken to relieve insomnia. Temazepam has been shown clinically to have hemodynamic side effects, particularly in the elderly; however, the mechanism is not clear. Zolpidem does not cause hemodynamic side effects. The purpose of this study was to determine whether the use of different hypnotics during spaceflight might contribute significantly to the high incidence of postflight orthostatic hypotension, and to compare the findings in astronauts with clinical research. Astronauts were separated into three groups: control (n = 40), temazepam (15 or 30 mg; n = 9), and zolpidem (5 or 10 mg; n = 8). In this study, temazepam and zolpidem were only taken the night before landing. The systolic and diastolic blood pressures and heart rates of the astronauts were measured during stand tests before spaceflight and on landing day. On landing day, systolic pressure decreased significantly and heart rate increased significantly in the temazepam group, but not in the control group or in the zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight when astronauts are hemodynamically compromised. Temazepam should not be the initial choice as a sleeping aid for astronauts. These results in astronauts may help to explain the hemodynamic side effects in the elderly who are also compromised. Zolpidem may be a better choice as a sleeping aid in these populations.

Adult↗
PubMed2003

Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function.

Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

Adult↗
PubMed2003

Cardiovascular effects of anti-G suit and cooling garment during space shuttle re-entry and landing.

BACKGROUND: Many cardiovascular changes associated with spaceflight reduce the ability of the cardiovascular system to oppose gravity on return to Earth, leaving astronauts susceptible to orthostatic hypotension during re-entry and landing. Consequently, an anti-G suit was developed to protect arterial pressure during re-entry. A liquid cooling garment (LCG) was then needed to alleviate the thermal stress resulting from use of the launch and entry suit. METHODS: We studied 34 astronauts on 22 flights (4-16 d). Subjects were studied 10 d before launch and on landing day. Preflight, crewmembers were suited with their anti-G suits set to the intended inflation for re-entry. Three consecutive measurements of heart rate and arterial pressure were obtained while seated and then again while standing. Three subjects who inflated the anti-G suits also donned the LCG for landing. Arterial pressure and heart rate were measured every 5 min during the de-orbit maneuver, through maximum G-loading (max-G) and touch down (TD). After TD, crew-members again initiated three seated measurements followed by three standing measurements. RESULTS: Astronauts with inflated anti-G suits had higher arterial pressure than those who did not have inflated anti-G suits during re-entry and landing (133.1 +/- 2.5/76.1 +/- 2.1 vs. 128.3 +/- 4.2/79.3 +/- 2.9, de-orbit; 157.3 +/- 4.5/102.1 +/- 3.6 vs. 145.2 +/- 10.5/95.7 + 5.5, max-G; 159.6 +/- 3.9/103.7 +/- 3.3 vs. 134.1 +/- 5.1/85.7 +/- 3.1, TD). In the group with inflated anti-G suits, those who also wore the LCG exhibited significantly lower heart rates than those who did not (75.7 +/- 11.5 vs. 86.5 +/- 6.2, de-orbit; 79.5 +/- 24.8 vs. 112.1 +/- 8.7, max-G; 84.7 +/- 8.0 vs. 110.5 +/- 7.9, TD). CONCLUSIONS: The anti-G suit is effective in supporting arterial pressure. The addition of the LCG lowers heart rate during re-entry.

Adult↗
PubMed2002

Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance.

About 20% of astronauts suffer postspaceflight presyncope. We studied pre- to postflight (5- to 16-day missions) cardiovascular responses to standing in 35 astronauts to determine differences between 1) men and women and 2) presyncopal and nonpresyncopal groups. The groups were presyncopal women, presyncopal men, and nonpresyncopal men based on their ability to stand for 10 min postflight. Preflight, women and presyncopal men had low vascular resistance, with the women having the lowest. Postflight, women experienced higher rates of presyncope (100 vs. 20%; P = 0.001) and greater losses of plasma volume (20 vs. 7%; P < 0.05) than men. Also, presyncopal subjects had lower standing mean arterial pressure (P < or = 0.001) and vascular resistance (P < 0.05), smaller increases in norepinephrine (P < or = 0.058) and greater increases in epinephrine (P < or = 0.058) than nonpresyncopal subjects. Presyncopal subjects had a strong dependence on plasma volume to maintain standing stroke volume. These findings suggest that postflight presyncope is greatest in women, and this can be ascribed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic responses. Conversely, high vascular resistance and postflight hyperadrenergic responses prevent presyncope.

Adult↗
PubMed2002

Comparison of echocardiographic changes after short- and long-duration spaceflight.

BACKGROUND: Previous echocardiographic studies of astronauts before and after short-duration (4-17 d) missions have demonstrated a decrease in resting left ventricular stroke volume, but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long-duration (129-144 d) spaceflight have been rare and their overall results equivocal. METHODS: Echocardiographic measurements (M-mode, 2-D, and Doppler) were obtained from short-duration (n = 13) and long-duration (n = 4) crewmembers to evaluate cardiac chamber sizes and function. RESULTS: Compared with short-duration astronauts, long-duration crewmembers had decreases in EF (+6+/-0.02 vs. -10.5+/-0.03%, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07%, p = 0.015), and an increase in left ventricular end systolic volume (-12+/-0.06 vs. +39+/-0.24%, p = 0.011). CONCLUSIONS: These data suggest a reduction in cardiac function that relates to mission duration. As the changes in BP and circulating blood volume are reported to be similar after short- and long-duration flights, the smaller EF after longer spaceflights may be due to a decrease in cardiac function rather than altered blood volume.

Adult↗