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At least 181 records · Page 10

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Clinical Trial↗

Program to study optimal protocol for cardiovascular and muscular efficiency

Two possible ways to minimize the effects of deconditioning in space are; To achieve a very high level of conditioning immediately prior to flight, and to provide a regimen in the capsule which will maintain a moderate degree of fitness. It was determined that running and riding a bicycle ergometer at comparable heart rates produced similar gains in physical fitness variables. It was found that subjects who exercised at a 180 heart rate made greater gains in physical fitness than did those exercising at a 140 or 160 heart rate. When the length of the workout was varied, subjects exercising sixty minutes per day made greater gains than those exercising twenty or forty minutes per day. Subjects who discontinued training slowly deconditioned, but a moderate level of fitness could be maintained by exercising at a pulse rate of 160 beats per minute for twenty minute periods three times a week. Subjects who overtrained twice daily to near exhaustion increased in fitness.

Olree, H. D.↗

Heart rate-left ventricular ejection time relations - Variations during postural change and cardiovascular challenges

Experiments were conducted on healthy human subjects to determine HR-LVET (Heart Rate-Left Ventricular Ejection Time) regression relations in different postures, including tilt, and during isometric exercise. The subjects were tested in the resting state in supine and sitting positions, during isometric handgrip in supine and sitting positions and during 70 deg headup tilt. The recordings included a bipolar electrocardiogram and a right external carotid pulse curve. Comparison of the HR-LVET relation for the conditions under analysis revealed differences among the respective regression equations, which can be explained by the well-established differences in stroke volume and ejection rate among these states. These differences appear to account for the fact that under conditions in which stroke volume variations should be the major determinant, slopes will be similar but intercepts will vary. Since substantial differences among intercepts are observed, caution should be exercised whenever the intercept factor is used to predict LVET for HR.

Lance, V. Q.↗

Chapter 6: Evaluation of Cardiothermal Model Prediction of Simulated Lunar Extravehicular Activity

Fewer than 20 extravehicular activities were completed during the Apollo program. The lunar environment has consistent unknowns to address particularly that of suited performance in partial gravity. The moon has altered gravity that is 1/6th that of Earth’s. This study is focused to investigate validation of the regression techniques identified in subsequent chapters and look to improve predictive outcomes during simulated lunar EVA tasks. Heart rate predictions of metabolic energy expenditure are investigated to predict workload throughout simulated lunar EVA conducted in the active response gravity offload system (ARGOS) with in the NASA Mark III space suit. Heart rate variability metrics are utilized to identify periods of high workload. Continually, the lunar offload capacity is further characterized to aid in improving the cardiothermal prediction models including predictions of core temperature, skin temperature and heat storage using heart rate, metabolic rates and suit thermal data during the simulated EVA. The outcome of this model provides an application for future use in contingency predictions of energy expenditure during Lunar EVAs and provide a suite of instrumentation to predict workload during training scenarios.

Simulated EVA↗

Uterine Contraction Modeling and Simulation

Building a training system for medical personnel to properly interpret fetal heart rate tracing requires developing accurate models that can relate various signal patterns to certain pathologies. In addition to modeling the fetal heart rate signal itself, the change of uterine pressure that bears strong relation to fetal heart rate and provides indications of maternal and fetal status should also be considered. In this work, we have developed a group of parametric models to simulate uterine contractions during labor and delivery. Through analysis of real patient records, we propose to model uterine contraction signals by three major components: regular contractions, impulsive noise caused by fetal movements, and low amplitude noise invoked by maternal breathing and measuring apparatus. The regular contractions are modeled by an asymmetric generalized Gaussian function and least squares estimation is used to compute the parameter values of the asymmetric generalized Gaussian function based on uterine contractions of real patients. Regular contractions are detected based on thresholding and derivative analysis of uterine contractions. Impulsive noise caused by fetal movements and low amplitude noise by maternal breathing and measuring apparatus are modeled by rational polynomial functions and Perlin noise, respectively. Experiment results show the synthesized uterine contractions can mimic the real uterine contractions realistically, demonstrating the effectiveness of the proposed algorithm.

Liu, Miao↗

System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy

We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.

Non-NASA Center↗

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

NASA Discipline Cardiopulmonary↗

Fluid volumes changes induced by spaceflight

The blood volume (BV), plasma volume (PV), and extracellular fluid volume changes produced in crewmembers during spaceflights of 11-84 days were compared to changes after 14 or 28 days of bedrest. Spaceflight and bedrest produce approximately equal BV changes but the recorded PV change after spaceflight was less. However, the diurnal change in PV may explain the smaller decreases recorded after spaceflight. The cardiovascular deconditioning caused by spaceflight and bedrest was compared using the mean heart rate response to lower body negative pressure (LBNP) testing at -50 mmHg pressure. These tests show approximately equal LBNP produced heart rate changes after bedrest and spaceflight. A countermeasure which includes 4 hr of LBNP treatment at -30 mmHg and the ingestion of one l. of saline was studied and found capable of returning the heart rate response and the PV of bedrested subjects to control (prebedrest) levels suggesting that it would be useful to the crewmembers after a spaceflight.

Johnson, P. C.↗

Orthostatic function during a stand test before and after head-up or head-down bedrest

The effects of head-down or head-up bedrest at -5, +10, +20, or +42 deg (simulating 0, 1/6, 1/3, and 2/3 g, respectively) for 6 hrs on four different days on the orthostatic tolerance were investigated by measuring relevant physiological reactions to orthostatic test taken before and after bedrest sessions. The multivariate analysis of variance statistical analyses indicates that there was no angle effect on any of the cardiovascular parameters monitored during the last 3 min of the stand test, suggesting that partial gravity loads would have no effect on the cardiovascular deconditioning exhibited postflight. There was, however, a significant elevation in the heart rate post-bedrest, and the heart rate increased on standing. Results from the stand test pre- and post-bedrest at -5 deg (but not at +10, +20, and +42 deg) were similar to those observed after space flight.

Lathers, Claire M.↗

Detection and Prevention of Cardiac Arrhythmias During Space Flight

There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Our hypothesis is that prolonged exposure to microgravity will alter T wave alternans measurements, decrease heart rate variance, increase QT dispersion, decrease heart rate recovery and alter QT restitution curve. A recently published study has shown that long duration spaceflights prolong cardiac conduction and repolarization. They concluded that long duration flight is associated with QT interval prolongation and may increase arrhythmia susceptibility. We propose using computer technology as a noninvasive clinical tool to detect and study clinically significant TWA during standard exercise testing using electrode systems specifically adapted for the purpose of obtaining and measuring TWA. A population of approximately 15 healthy men and 5 healthy women subjects, representative of the astronaut cohort will be asked to voluntarily participate in this study. Their blood pressure and ECG/TWA will be measured pre-flight and in-flight. Prior to flight, subjects will be asked to participate in an orientation session. Still photos will be taken of the skin where the conductive gel is used for the multi-segment sensors. Photos will be recorded preflight, immediately postflight, and several times during the proceeding week until it has been determined that any skin reaction has disappeared or that no rash is present and will not appear.

Pillai, Dilip↗

NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats

The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.

NASA Discipline Cardiopulmonary↗

Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias

This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

Clinical Trial↗

Maximal exercise as a countermeasure to orthostatic intolerance after spaceflight

Previous investigators have suggested that maximal exercise performed 24 h before the end of bed rest, a spaceflight analog, restores prebed rest plasma volume, baroreflex responses, and orthostatic tolerance. PURPOSE: In this case report, we examined the effect of a similar exercise protocol 24 h before a Shuttle landing on the orthostatic responses of four crewmembers (EX) after spaceflights of 8-14 d. Four additional crewmembers (CON) served as controls and did not perform exercise during the final day of the flight. METHODS: Each crewmember performed a 10-min stand test approximately 10 d before launch (L-10) and within 1-2 h of landing (R+0). Cardiac stroke volume was measured (Doppler ultrasound) supine and during each min of standing for three EX and three CON subjects. RESULTS: Preflight, all crewmembers completed the stand test and each group had similar heart rate and blood pressure responses. Postflight, all subjects also completed the 10-min stand test. Each group had similarly elevated supine and standing heart rates, elevated diastolic and mean arterial blood pressures, and reduced pulse pressures compared to L-10. However, postflight cardiac output, mean +/- SEM, (EX: 4.5+/-0.6 L x min(-1); CON: 3.1+/-0.3 L x min(-1)) and stroke volume (EX: 43+/-7 mL x beat; CON: 30+/-6 mL x beat) were higher after 10 min standing in the EX subjects compared to CON subjects. CONCLUSIONS: For these four crewmembers, maximal exercise performed 24 h before landing may have helped maintain stroke volume but did not maintain heart rate and blood pressure responses during standing compared to preflight.

Flight Experiment↗

Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

Kumagai, Kazuhiro↗

Fractal fluctuations in cardiac time series

Human heart rate, controlled by complex feedback mechanisms, is a vital index of systematic circulation. However, it has been shown that beat-to-beat values of heart rate fluctuate continually over a wide range of time scales. Herein we use the relative dispersion, the ratio of the standard deviation to the mean, to show, by systematically aggregating the data, that the correlation in the beat-to-beat cardiac time series is a modulated inverse power law. This scaling property indicates the existence of long-time memory in the underlying cardiac control process and supports the conclusion that heart rate variability is a temporal fractal. We argue that the cardiac control system has allometric properties that enable it to respond to a dynamical environment through scaling.

NASA Discipline Cardiopulmonary↗

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

Non-NASA Center↗

Splanchnic Compression Improves the Efficacy of Compression Stockings to Prevent Orthostatic Intolerance

Purpose: Post-spaceflight orthostatic intolerance (OI) is observed in 20-30% of astronauts. Previous data from our laboratory suggests that this is largely a result of decreased venous return. Currently, NASA astronauts wear an anti-gravity suit (AGS) which consists of inflatable air bladders over the calves, thighs and abdomen, typically pressurized from 26 to 78 mmHg. We recently determined that, thigh-high graded compression stockings (JOBST , 55 mmHg at ankle, 6 mmHg at top of thigh) were effective, though to a lesser degree than the AGS. The purpose of this study was to evaluate the addition of splanchnic compression to prevent orthostatic intolerance. Methods: Ten healthy volunteers (6M, 4F) participated in three 80 head-up tilts on separate days while (1) normovolemic (2) hypovolemic w/ breast-high compression stockings (BS)(JOBST(R), 55 mmHg at the ankle, 6 mmHg at top of thigh, 12 mmHg over abdomen) (3) hypovolemic w/o stockings. Hypovolemia was induced by IV infusion of furosemide (0.5 mg/kg) and 48 hrs of a low salt diet to simulate plasma volume loss following space flight. Hypovolemic testing occurred 24 and 48 hrs after furosemide. One-way repeated measures ANOVA, with Bonferroni corrections, was used to test for differences in blood pressure and heart rate responses to head-up tilt, stand times were compared using a Kaplan-Meyer survival analysis. Results: BS were effective in preventing OI and presyncope in hypovolemic test subjects ( p = 0.015). BS prevented the decrease in systolic blood pressure seen during tilt in normovolemia (p < 0.001) and hypovolemia w/o countermeasure (p = 0.005). BS also prevented the decrease in diastolic blood pressure seen during tilt in normovolemia (p = 0.006) and hypovolemia w/o countermeasure (p = 0.041). Hypovolemia w/o countermeasure showed a higher tilt-induced heart rate increase (p = 0.022) than seen in normovolemia; heart rate while wearing BS was not different than normovolemia (p = 0.353). Conclusion: BS may be an effective countermeasure to post-space flight OI. The addition of splanchnic compression is more effective than the previous thigh-high garments. These stockings are readily available, inexpensive, and can be worn for days following landing as astronauts re-adapt to Earth gravity.

Platts, Steven H.↗

Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans

1. Prior findings suggest that baroreflexes are capable of modulating skin blood flow, but the effects of baroreceptor loading/unloading on sweating are less clear. Therefore, this project tested the hypothesis that pharmacologically induced alterations in arterial blood pressure in heated humans would lead to baroreflex-mediated changes in both skin sympathetic nerve activity (SSNA) and sweat rate. 2. In seven subjects mean arterial blood pressure was lowered (approximately 8 mmHg) and then raised (approximately 13 mmHg) by bolus injections of sodium nitroprusside and phenylephrine, respectively. Moreover, in a separate protocol, arterial blood pressure was reduced via steady-state administration of sodium nitroprusside. In both normothermia and heat-stress conditions the following responses were monitored: sublingual and mean skin temperatures, heart rate, beat-by-beat blood pressure, skin blood flow (laser-Doppler flowmetry), local sweat rate and SSNA (microneurography from peroneal nerve). 3. Whole-body heating increased skin and sublingual temperatures, heart rate, cutaneous blood flow, sweat rate and SSNA, but did not change arterial blood pressure. Heart rate was significantly elevated (from 74 +/- 3 to 92 +/- 4 beats x min(-1); P < 0.001) during bolus sodium nitroprusside-induced reductions in blood pressure, and significantly reduced (from 92 +/- 4 to 68 +/- 4 beats x min(-1); P < 0.001) during bolus phenylephrine-induced elevations in blood pressure, thereby demonstrating normal baroreflex function in these subjects. 4. Neither SSNA nor sweat rate was altered by rapid (bolus infusion) or sustained (steady-state infusion) changes in blood pressure regardless of the thermal condition. 5. These data suggest that SSNA and sweat rate are not modulated by arterial baroreflexes in normothermic or moderately heated individuals.

Clinical Trial↗