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David Robertson - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Intolerance and vasovagal syncope after spaceflight
2015Co-Authors: Andre Diedrich, Kyle Timothy Mandsager, David RobertsonAbstract:Postflight Orthostatic Intolerance is commonly observed in astronauts after their return to Earth. It is defined as the development of symptomatic Intolerance to upright posture after flight, with concomitant tachycardia and progressive hypotension. With sustained upright posture, progression to frank vasovagal syncope is possible, though rare. This phenomenon is a consequence of several physiologic and autonomic adaptations that occur during spaceflight, including loss of plasma volume, muscle mass, cardiac atrophy, loss of vasoconstrictor function, vestibular dysfunction, and alterations in autonomic function. A variety of in-flight and postflight countermeasures have been developed to counteract these neurophysiologic consequences of spaceflight.
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Influence of an Insertion Variant in the 5ʹUTR of the Endothelin-1 Gene on Orthostatic Intolerance
The American Journal of the Medical Sciences, 2005Co-Authors: Robert Winker, David Robertson, Ivo Ponocny, Andre Diedrich, Italo Biaggioni, Hugo W. Rüdiger, Emily M. Garland, Ingolf CascorbiAbstract:ABSTRACT: Background Orthostatic Intolerance is a multifactorial disease in which the genetic contribution is probably the result of a number of genes acting in combination. Recent work has shown that Orthostatic Intolerance is influenced by endothelial nitric oxide synthase gene polymorphisms. Since endothelin-1 (ET-1) is one of the most important vasoconstrictor peptides, a frequent adenine insertion polymorphism within the 5ʹ-untranslated region (5ʹUTR), which is of functional importance for ET-1 expression, could influence Orthostatic Intolerance. The aim of this study was therefore to ascertain whether this frequent variant of the endothelin-1 gene influences the risk for Orthostatic Intolerance. Methods We studied 257 white patients (120 cases with Orthostatic Intolerance and 137 controls) for genotyping of the 5ʹUTR I variant. From this cohort, 111 patients and 99 control subjects underwent a tilttable test or an upright posture study, including monitoring of blood pressure, heart rate, and plasma catecholamines, in the supine position and during 30 minutes of standing. Genotyping was performed in all participants. χ 2 tests of independence were used to test for associations between Orthostatic Intolerance and genotype. In addition, an association of the insertion polymorphism with hemodynamic variables (heart rate, supine and upright blood pressure) was ascertained using one-way analysis of variance. Results The 5ʹUTR I variant was significantly less common in patients with Orthostatic Intolerance (allele frequency 0.36 and 0.28, in controls and cases, respectively). Additionally, we found a significant decrease in the risk of Orthostatic Intolerance among people who were homozygous for the 5ʹUTR variant (I/I) compared with the wild-type variant (D/D) (odds ratio, 0.41; 95% confidence interval, 0.17 to 0.97; P = 0.04). No association between the 5ʹUTR variant and heart rate or blood pressure regardless of diagnosis was found. Conclusions Our current results suggest that the hereditary adenine insertion variant in the 5ʹ-UTR of the endothelin-1 gene is protective for Orthostatic Intolerance. The increased ET-1 protein expression that has been linked with the I variant might be associated with a more efficient hemodynamic response to standing. This is likely one of several common genetic loci that may represent modifiers of Orthostatic Intolerance phenotypes.
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endurance exercise training in Orthostatic Intolerance a randomized controlled trial
Hypertension, 2005Co-Authors: Robert Winker, David Robertson, Alfred Barth, Daniela Bidmon, Ivo Ponocny, Michael Weber, Otmar Mayr, Andre Diedrich, Richard Maier, Alex PilgerAbstract:Orthostatic Intolerance is a syndrome characterized by chronic Orthostatic symptoms of light-headedness, fatigue, nausea, Orthostatic tachycardia, and aggravated norepinephrine levels while standing. The aim of this study was to assess the protective effect of exercise endurance training on Orthostatic symptoms and to examine its usefulness in the treatment of Orthostatic Intolerance. 2768 military recruits were screened for Orthostatic Intolerance by questionnaire. Tilt-table testing identified 36 cases of Orthostatic Intolerance out of the 2768 soldiers. Subsequently, 31 of these subjects with Orthostatic Intolerance entered a randomized, controlled trial. The patients were allocated randomly to either a “training” (3 months jogging) or a “control” group. The influence of exercise training on Orthostatic Intolerance was assessed by determination of questionnaire scores and tilt-table testing before and after intervention. After training, only 6 individuals of 16 still had Orthostatic Intolerance compared with 10 of 11 in the control group. The Fisher exact test showed a highly significant difference in diagnosis between the 2 groups ( P =0.008) at the end of the study. Analysis of the questionnaire-score showed significant interaction between time and group ( P =0.001). The trained subjects showed an improvement in the average symptom score from 1.79±0.4 to 1.04±0.4, whereas the control subjects showed no significant change in average symptom score (2.09±0.6 and 2.14±0.5, respectively). Our data demonstrate that endurance exercise training leads to an improvement of symptoms in the majority of patients with Orthostatic Intolerance. Therefore, we suggest that endurance training should be considered in the treatment of Orthostatic Intolerance patients.
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Effects of standing on cerebrovascular resistance in patients with idiopathic Orthostatic Intolerance
The American Journal of Medicine, 2004Co-Authors: Giris Jacob, Jens Jordan, John R. Shannon, Raffaello Furlan, Bonnie K Black, Denis S Atkinson, David RobertsonAbstract:PURPOSE: Patients with idiopathic Orthostatic Intolerance often have debilitating symptoms on standing that are suggestive of cerebral hypoperfusion despite the absence of Orthostatic hypotension. SUBJECTS AND METHODS: We evaluated the effects of graded head-up tilt on cerebral blood flow as determined by transcranial Doppler measurements in 10 patients with idiopathic Orthostatic Intolerance (nine women, one man, 22 to 47 years) and nine age- and sex-matched control subjects. RESULTS: In patients, mean (+/- SD) arterial pressure at 0 degrees head-up tilt was 90 +/- 11 mm Hg and was well maintained at all tilt angles (90 +/- 11 mm Hg at 75 degrees). In controls, mean arterial pressure was 85 +/- 7 mm Hg at 0 degrees and 82 +/- 11 mm Hg at 75 degrees head-up tilt. There was a substantial decrease in peak velocity with increasing tilt angle in patients (28% +/- 10%) but not in controls (10% +/- 10% at 75 degrees, P
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No increased herniation of the cerebellar tonsils in a group of patients with Orthostatic Intolerance.
Clinical Autonomic Research, 2002Co-Authors: Emily M. Garland, Bonnie K Black, James C. Anderson, Robert M. Kessler, Peter E. Konrad, David RobertsonAbstract:Orthostatic Intolerance, seen predominantly in young women, is characterized by symptoms of lightheadedness, fatigue and palpitations in the upright posture. With standing, plasma norepinephrine levels rise dramatically and heart rate often increases by more than 30 beats per minute, although blood pressure does not usually fall. A theory recently popularized in the media suggests that some cases of Orthostatic Intolerance are related to hindbrain compression, with or without a Chiari I malformation. As a preliminary investigation of this hypothesis, head or cervical spine MRI scans from 23 females with Orthostatic Intolerance were reviewed. The cerebellar tonsils averaged 0.3 ± 1.9 mm below the foramen magnum. These results were compared to measurements from a control group averaging 0.4 ± 2.6 mm above the foramen magnum (P > 0.05). Tonsillar depression of at least 3 mm occurred in 13 % of both the patient group and the control group. Tonsillar herniation was not found to influence supine or upright blood pressure, heart rate or plasma norepinephrine levels in the patients. We conclude that herniation of the cerebellar tonsils is not a common cause of Orthostatic Intolerance. However, the single measurement of tonsillar depression might underestimate the number of patients with hindbrain compression.
Giris Jacob - One of the best experts on this subject based on the ideXlab platform.
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Effects of standing on cerebrovascular resistance in patients with idiopathic Orthostatic Intolerance
The American Journal of Medicine, 2004Co-Authors: Giris Jacob, Jens Jordan, John R. Shannon, Raffaello Furlan, Bonnie K Black, Denis S Atkinson, David RobertsonAbstract:PURPOSE: Patients with idiopathic Orthostatic Intolerance often have debilitating symptoms on standing that are suggestive of cerebral hypoperfusion despite the absence of Orthostatic hypotension. SUBJECTS AND METHODS: We evaluated the effects of graded head-up tilt on cerebral blood flow as determined by transcranial Doppler measurements in 10 patients with idiopathic Orthostatic Intolerance (nine women, one man, 22 to 47 years) and nine age- and sex-matched control subjects. RESULTS: In patients, mean (+/- SD) arterial pressure at 0 degrees head-up tilt was 90 +/- 11 mm Hg and was well maintained at all tilt angles (90 +/- 11 mm Hg at 75 degrees). In controls, mean arterial pressure was 85 +/- 7 mm Hg at 0 degrees and 82 +/- 11 mm Hg at 75 degrees head-up tilt. There was a substantial decrease in peak velocity with increasing tilt angle in patients (28% +/- 10%) but not in controls (10% +/- 10% at 75 degrees, P
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Orthostatic Intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team.
Pflügers Archiv: European Journal of Physiology, 2000Co-Authors: David Robertson, Jens Jordan, John R. Shannon, Andre Diedrich, Giris Jacob, Italo Biaggioni, Raffaello Furlan, Andrew C. Ertl, Robert P. Carson, And TeamAbstract:Orthostatic Intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the Orthostatic Intolerance that occurs on Earth in individuals with Orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial Orthostatic Intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented.
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Orthostatic Intolerance a disorder of young women
Obstetrical & Gynecological Survey, 2000Co-Authors: Nicole Daamen, Jens Jordan, John R. Shannon, Giris Jacob, Italo Biaggioni, David RobertsonAbstract:Orthostatic Intolerance (OI) is a cause of significant disability in otherwise healthy women seen by gynecologists. Orthostatic tachycardia is often the most obvious hemodynamic abnormality found in OI patients, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, fainting (syncope). It is the most common disorder of blood pressure regulation after essential hypertension, and patients with OI are traditionally women of childbearing age. Estimates suggest that at least 500,000 Americans suffer from some form of OI, and such patients comprise the largest group referred to centers specialized in autonomic disorders. This article reviews recent advances made in the understanding of this condition, potential pathophysiological mechanisms contributing to Orthostatic Intolerance, and therapeutic alternatives currently available for the management of these patients.
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Orthostatic Intolerance and tachycardia associated with norepinephrine transporter deficiency
The New England Journal of Medicine, 2000Co-Authors: John R. Shannon, Jens Jordan, Giris Jacob, Italo Biaggioni, Nancy Flattem, Bonnie K Black, Randy D Blakely, David RobertsonAbstract:BACKGROUND: Orthostatic Intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of Orthostatic Intolerance. METHODS: In a patient with Orthostatic Intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to Orthostatic Intolerance.
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idiopathic Orthostatic Intolerance and postural tachycardia syndromes
The American Journal of the Medical Sciences, 1999Co-Authors: Giris Jacob, Italo BiaggioniAbstract:Upright posture imposes a substantial gravitational stress on the body, for which we are able to compensate, in large part because of the autonomic nervous system. Alteration in autonomic function, therefore, may lead to Orthostatic Intolerance. On one extreme, patients with autonomic failure caused by degenerative loss of autonomic function are severely disabled by Orthostatic hypotension and may faint whenever they stand up. Fortunately, such patients are relatively rare. On the other hand, disabling Orthostatic Intolerance can develop in otherwise normal young people. These patients can be severely impaired by symptoms of fatigue, tachycardia, and shortness of breath when they stand up. The actual incidence of this disorder is unknown, but these patients make up the largest group of patients referred to centers that specialize in autonomic disorders. We will review recent advances made in the understanding of this condition, potential pathophysiological mechanisms that contribute to Orthostatic Intolerance, therapeutic alternatives currently available for the management of these patients, and areas in which more research is needed.
Donald E. Watenpaugh - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Intolerance after spaceflight
Journal of Applied Physiology, 1996Co-Authors: J. C. Buckey, F. A. Gaffney, Lynda D. Lane, Benjamin D. Levine, Donald E. Watenpaugh, S J Wright, Willie E Moore, C G BlomqvistAbstract:Orthostatic Intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three sp...
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Mechanisms of post-flight Orthostatic Intolerance.
Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 1994Co-Authors: C G Blomqvist, J. C. Buckey, F. A. Gaffney, Lynda D. Lane, Benjamin D. Levine, Donald E. WatenpaughAbstract:Post-flight Orthostatic Intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic Intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The Intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of Orthostatic Intolerance. Language: en
C G Blomqvist - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Intolerance after spaceflight
Journal of Applied Physiology, 1996Co-Authors: J. C. Buckey, F. A. Gaffney, Lynda D. Lane, Benjamin D. Levine, Donald E. Watenpaugh, S J Wright, Willie E Moore, C G BlomqvistAbstract:Orthostatic Intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three sp...
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Mechanisms of post-flight Orthostatic Intolerance.
Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 1994Co-Authors: C G Blomqvist, J. C. Buckey, F. A. Gaffney, Lynda D. Lane, Benjamin D. Levine, Donald E. WatenpaughAbstract:Post-flight Orthostatic Intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic Intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The Intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of Orthostatic Intolerance. Language: en
Benjamin D. Levine - One of the best experts on this subject based on the ideXlab platform.
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hemodynamics of Orthostatic Intolerance implications for gender differences
American Journal of Physiology-heart and Circulatory Physiology, 2004Co-Authors: Qi Fu, Armin Arbabzadeh, Merja A Perhonen, Rong Zhang, Julie H Zuckerman, Benjamin D. LevineAbstract:Women have a greater incidence of Orthostatic Intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced re...
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Orthostatic Intolerance after spaceflight
Journal of Applied Physiology, 1996Co-Authors: J. C. Buckey, F. A. Gaffney, Lynda D. Lane, Benjamin D. Levine, Donald E. Watenpaugh, S J Wright, Willie E Moore, C G BlomqvistAbstract:Orthostatic Intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three sp...
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Mechanisms of post-flight Orthostatic Intolerance.
Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 1994Co-Authors: C G Blomqvist, J. C. Buckey, F. A. Gaffney, Lynda D. Lane, Benjamin D. Levine, Donald E. WatenpaughAbstract:Post-flight Orthostatic Intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic Intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The Intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of Orthostatic Intolerance. Language: en
