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At least 469 records · Page 26

Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.

Review↗

Lysine hydroxylation of collagen in a fibroblast cell culture system

The lysine (Lys) hydroxylation pattern of type I collagen produced by human fibroblasts in culture was analyzed and compared. Fibroblasts were cultured from normal human skin (NSF), keloid (KDF), fetal skin (FDF), and skin tissues of Ehlers-Danlos syndrome type VIA and VIB patients (EDS-VIA and -VIB). The type I collagen alpha chains with or without non-helical telopeptides were purified from the insoluble matrix and analyzed. In comparison with NSFs, KDF and FDF showed significantly higher Lys hydroxylation, particularly in the telopeptide domains of both alpha chains. Both EDS-VIA and -VIB showed markedly lower Lys hydroxylation in the helical domains of both alpha chains whereas that in the telopeptides was comparable with those of NSFs. A similar profile was observed in the tissue sample of the EDS-VIB patient. These results demonstrate that the Lys hydroxylation pattern is domain-specific within the collagen molecule and that this method is useful to characterize the cell phenotypes in normal/pathological connective tissues.

NASA Discipline Cell Biology↗

Real-time three-dimensional color doppler evaluation of the flow convergence zone for quantification of mitral regurgitation: Validation experimental animal study and initial clinical experience

BACKGROUND: Pitfalls of the flow convergence (FC) method, including 2-dimensional imaging of the 3-dimensional (3D) geometry of the FC surface, can lead to erroneous quantification of mitral regurgitation (MR). This limitation may be mitigated by the use of real-time 3D color Doppler echocardiography (CE). Our objective was to validate a real-time 3D navigation method for MR quantification. METHODS: In 12 sheep with surgically induced chronic MR, 37 different hemodynamic conditions were studied with real-time 3DCE. Using real-time 3D navigation, the radius of the largest hemispherical FC zone was located and measured. MR volume was quantified according to the FC method after observing the shape of FC in 3D space. Aortic and mitral electromagnetic flow probes and meters were balanced against each other to determine reference MR volume. As an initial clinical application study, 22 patients with chronic MR were also studied with this real-time 3DCE-FC method. Left ventricular (LV) outflow tract automated cardiac flow measurement (Toshiba Corp, Tokyo, Japan) and real-time 3D LV stroke volume were used to quantify the reference MR volume (MR volume = 3DLV stroke volume - automated cardiac flow measurement). RESULTS: In the sheep model, a good correlation and agreement was seen between MR volume by real-time 3DCE and electromagnetic (y = 0.77x + 1.48, r = 0.87, P <.001, delta = -0.91 +/- 2.65 mL). In patients, real-time 3DCE-derived MR volume also showed a good correlation and agreement with the reference method (y = 0.89x - 0.38, r = 0.93, P <.001, delta = -4.8 +/- 7.6 mL). CONCLUSIONS: real-time 3DCE can capture the entire FC image, permitting geometrical recognition of the FC zone geometry and reliable MR quantification.

Validation Studies↗

Immune function during space flight

It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.

manned↗

T wave alternans threshold late after repair of tetralogy of Fallot

INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) is a marker of increased risk for malignant ventricular arrhythmia. There is a significant risk of arrhythmia and sudden death after repair of congenital heart disease. The aim of this study was to determine the prevalence and characteristics of TWA after repair of tetralogy of Fallot (TOF). METHODS AND RESULTS: TWA was evaluated during bicycle exercise in 49 subjects who had consecutively undergone transatrial-transpulmonary repair. Median values for age, age at repair, and follow-up duration were 14.9 years (11.5-20.8), 1.6 years (0.2-4.9), and 11.6 years (9.4-17.2), respectively. All patients were in New York Heart Association functional class I and were asymptomatic. Median QRS duration was 120 msec (80-150). Sustained TWA was detected in 7 (23%) of 31 subjects with adequate tests. In these 7 subjects, median onset heart rate (HR) was 120 (98-155). Median HR threshold as a percentage of predicted maximum HR (220 - age) was 58% (48-77). Sustained TWA prevalence was not significantly different compared with normal subjects (7/31 vs 9/83; P = 0.1). Onset HR in the TOF group was significantly lower [mean (SD) of 122 (20) vs 139 (12), P < 0.05]. In the TOF group with sustained TWA, the TWA occurred in 4 of 7 at <60% predicted maximum HR versus 1 of 9 normal subjects (P < 0.05); 3 of 7 had onset HR <120 versus 0 of 9 normal subjects (P < 0.03). There was no significant difference in age, gender, transannular patch use, restrictive right ventricular physiology, QRS duration, QTc, QT/QRS dispersion, or nonsustained ventricular tachycardia in subjects with or those without sustained TWA. CONCLUSION: The onset HR for sustained TWA is significantly lower after repair of TOF. Further study is required to determine whether this represents an increased risk for arrhythmia in this patient group.

Non-NASA Center↗

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Non-NASA Center↗

Pulmonary venous flows reflect changes in left atrial hemodynamics during mitral balloon valvotomy

Patients with mitral stenosis have usually blunted pulmonary venous (PV) flow, because of decreased mitral valve area and diastolic dysfunction. The authors compared changes in Doppler PV velocities by using transesophageal echocardiography (TEE) against hemodynamics parameters before and after mitral balloon valvotomy to observe relevance of PV velocities and endsystolic left atrial (LA) pressure-volume relationship. In 25 patients (aged 35 +/- 17 years) with mitral stenosis in sinus rhythm, changes in LA pressure and volumes were compared with PV velocities before and after valvotomy. Mitral valve area, mitral gradients, and deceleration time were obtained. Mitral valve area and mitral gradients changed from 1 +/- 0.2 cm2 and 14.6 +/- 5.4 mmHg to 1.9 +/- 0.3 cm2 and 6.3 +/- 1.7 mmHg, respectively (p<0.001). AR peak reverse flow velocity and AR duration decreased from 29 +/- 13 cm/s and 110 =/- 30 msec to 19 +/- 6 cm/s and 80 +/- 29 msec respectively (p<0.001). Transmitral Doppler E wave deceleration time decreased from 327 +/- 85 to 209 +/- 61 s and cardiac output increased from 4.2 +/- 1.0 to 5.2 +/- 1.1 L/minute (p<0.001). The changes in LA pressure were correlated with changes in S/D (r=0.57, p<0.05). The changes in endsystolic LA pressure-volume relationship were also correlated with changes in S/D (r=0.52, p<0.05). Endsystolic LA pressure-volume relationship decreased after mitral balloon valvotomy, as a result of a large decrease in pressure. PV systolic/diastolic (S/D) waves ratio reflects endsystolic LA pressure-volume relationship and may be used as another indicator of successful valvotomy.

Non-NASA Center↗

Is Doppler tissue velocity during early left ventricular filling preload independent?

BACKGROUND: Transmitral Doppler flow indices are used to evaluate diastolic function. Recently, velocities measured by Doppler tissue imaging have been used as an index of left ventricular relaxation. OBJECTIVE: To determine whether Doppler tissue velocities are influenced by alterations in preload. METHODS: Left ventricular preload was altered in 17 patients (all men, mean (SD) age, 49 (8) years) during echocardiographic measurements of left ventricular end diastolic volume, maximum left atrial area, peak early Doppler filling velocity, and left ventricular myocardial velocities during early filling. Preload altering manoeuvres included Trendelenberg (stage 1), reverse Trendelenberg (stage 2), and amyl nitrate (stage 3). Systolic blood pressure was measured at each stage. RESULTS: In comparison with baseline, left ventricular end diastolic volume (p = 0.001), left atrial area (p = 0.003), peak early mitral Doppler filling velocity (p = 0.01), and systolic blood pressures (p = 0.001) were all changed by preload altering manoeuvres. Only left ventricular myocardial velocity during early filling remained unchanged by these manoeuvres. CONCLUSIONS: In contrast to standard transmitral Doppler filling indices, Doppler tissue early diastolic velocities are not significantly affected by physiological manoeuvres that alter preload. Thus Doppler tissue velocities during early left ventricular diastole may provide a better index of diastolic function in cardiac patients by providing a preload independent assessment of left ventricular filling.

Non-NASA Center↗

Ageing and water homeostasis

This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

Review↗

Obstructive apnea during sleep is associated with peripheral vasoconstriction

Obstructive apnea during sleep is associated with a substantial transient blood pressure elevation. The mechanism of this pressor response is unclear. In this study we measured muscle sympathetic nerve activity (MSNA), mean arterial pressure (Psa), and mean limb blood velocity as an index of blood flow (MBV, Doppler) and calculated changes in limb vascular resistance during and after apneas during both wakefulness and sleep in patients with the obstructive sleep apnea syndrome. Immediately postapnea during sleep Psa increased significantly compared with the earlier stages of apnea and this was preceded by a rise of MSNA (n = 5). In contrast to blood pressure, MBV remained unchanged. Because resistance = blood pressure/blood flow, limb vascular resistance increased by 29 +/- 8% from late apnea to postapnea (n = 7, p < 0.002). Voluntary breathhold maneuvers during room air exposure evoked similar responses (n = 10). Supplemental oxygen administered via nonrebreather face mask attenuated the MSNA and vasoconstrictor responses to obstructive (n = 2) and voluntary apneas (n = 10). Our data suggest that obstructive apneas in patients with the obstructive apnea syndrome are accompanied by transient limb vasoconstriction. This vasoconstrictor response appears to be, at least in part, mediated by the sympathetic nervous system and may be linked to hypoxia.

NASA Discipline Cardiopulmonary↗

Assessment of internal mammary artery and saphenous vein graft patency and flow reserve using transthoracic Doppler echocardiography

OBJECTIVE: To investigate transthoracic Doppler echocardiography in the identification of coronary artery bypass graft (CABG) flow for assessing graft patency. DESIGN: The initial study group comprised 45 consecutive patients with previous CABG undergoing elective cardiac catheterisation for recurrent ischaemia. The Doppler variables best correlated with angiographic graft patency were then tested prospectively in a further 84 patients (test group). SETTING: Three tertiary referral centres. INTERVENTIONS: Flow velocities in grafts were recorded at rest and during hyperaemia induced by dipyridamole (0.56 mg/kg/4 min), under the guidance of transthoracic colour Doppler flow mapping. Findings on transthoracic Doppler were compared with angiography. MAIN OUTCOME MEASURES: Feasibility of identifying open grafts by Doppler and diagnostic accuracy for Doppler detection of significant (>/= 70%) graft stenosis. RESULTS: In the test group the identification rate for mammary artery grafts was 100%, for saphenous vein grafts to left anterior descending coronary artery 91%, for vein grafts to right coronary artery 96%, and for vein grafts to circumflex artery 90%. Coronary flow reserve (the ratio between peak diastolic velocity under hyperaemia and at baseline) of < 1.9 (95% confidence interval 1.83 to 2.08) had 100% sensitivity, 98% specificity, 87.5% positive predictive value, and 100% negative predictive value for mammary artery graft stenosis. Coronary flow reserve of < 1.6 (95% CI 1.51 to 1.73) had 91% sensitivity, 87% specificity, 85.4% positive predictive value, and 92.3% negative predictive value for significant vein graft stenosis. CONCLUSIONS: Transthoracic Doppler can provide non-invasive assessment of CABG patency.

Multicenter Study↗

The autonomic laboratory

The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

NASA Discipline Cardiopulmonary↗

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.

Non-NASA Center↗

Gastric dysrhythmias and the current status of electrogastrography

Myoelectrical activity recorded simultaneously from mucosal, serosal, and cutaneous electrodes has confirmed that the 3-cpm signal from such electrodes reflects gastric slow-wave activity. Now, the observation that patients with unexplained nausea and vomiting may have very rapid slow-wave frequencies (tachygastrias) and very slow, slow-wave frequencies (bradygastrias) suggests that electrogastrography, a reliable and noninvasive technique, may be useful in the diagnosis and management of patients with upper abdominal symptoms and gastroparesis.

Non-NASA Center↗

The TERESA project: from space research to ground tele-echography

Ultrasound examinations represent one of the major diagnostic modalities of future healthcare. They are currently used to support medical space research but require a high skilled operator for both probe positioning on the patient's skin and image interpretation. TERESA is a tele-echography project that proposes a solution to bring astronauts and remotely located patients on ground quality ultrasound examinations despite the lack of a specialist at the location of the wanted medical act.

Space Flight/instrumentation↗

Percutaneous transluminal alcohol septal myocardial ablation after aortic valve replacement

When left ventricular outflow tract obstruction develops after aortic valve replacement, few treatment choices have been available until now. We present a patient with prior aortic valve replacement who developed left ventricle outflow tract obstruction that was successfully treated with a percutaneous transcoronary myocardial septal alcohol ablation. This technique is a useful tool for the treatment of obstructive hypertrophic cardiomyopathy, especially in those patients with prior heart surgery. Copyright 2001 Wiley-Liss, Inc.

Non-NASA Center↗

Noise effects on the complex patterns of abnormal heartbeats

Patients at high risk for sudden death often exhibit complex heart rhythms in which abnormal heartbeats are interspersed with normal heartbeats. We analyze such a complex rhythm in a single patient over a 12-h period and show that the rhythm can be described by a theoretical model consisting of two interacting oscillators with stochastic elements. By varying the magnitude of the noise, we show that for an intermediate level of noise, the model gives best agreement with key statistical features of the dynamics.

NASA Discipline Cardiopulmonary↗

Short-term hemodynamic performance of the mitral Carpentier-Edwards PERIMOUNT pericardial valve. Carpentier-Edwards PERIMOUNT Investigators

BACKGROUND: Although long-term durability data exist, little data are available concerning the hemodynamic performance of the Carpentier-Edwards PERIMOUNT pericardial valve in the mitral position. METHODS: Sixty-nine patients who were implanted with mitral PERIMOUNT valves at seven international centers between January 1996 and February 1997 consented to participate in a short-term echocardiography follow-up. Echocardiographs were collected at a mean of 600+/-133 days after implantation (range, 110 to 889 days); all underwent blinded core lab analysis. RESULTS: At follow-up, peak gradients were 9.09+/-3.43 mm Hg (mean, 4.36+/-1.79 mm Hg) and varied inversely with valve size (p < 0.05). The effective orifice areas were 2.5+/-0.6 cm2 and tended to increase with valve size (p = 0.08). Trace mitral regurgitation (MR) was common (n = 48), 9 patients had mild MR, 1 had moderate MR, none had severe MR. All MR was central (n = 55) or indeterminate (n = 3). No paravalvular leaks were observed. Mitral regurgitation flow areas were 3.4+/-2.8 cm2 and were without significant volumes. CONCLUSIONS: In this multicenter study, these mitral valves are associated with trace, although physiologically insignificant, central MR. Despite known echocardiographic limitations, the PERIMOUNT mitral valves exhibit similar hemodynamics to other prosthetic valves.

Clinical Trial↗