Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Vitamin D deficiency is associated with orthostatic hypotension in oldest-old women.

PubMed

Annweiler, C; Schott, A-M; Rolland, Y; Beauchet, O

2014-09-01

Orthostatic hypotension, a condition that mostly affects 'oldest-old' (i.e. ≥80 years) adults, is primarily explained by age-related dysfunction of blood pressure control. Vitamin D may contribute to blood pressure control. The aim of this study was to determine whether vitamin D deficiency is associated with orthostatic hypotension in oldest-old adults. Cross-sectional analysis at baseline of the EPIDOS study. Five French areas. A total of 329 community-dwelling oldest-old women (mean age 83.3 ± 0.2 years). Orthostatic hypotension was defined as a systolic blood pressure drop of ≥20 mmHg and/or a diastolic blood pressure drop of ≥10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25OHD) concentration ≤10 ng mL(-1) . Covariates included in the models were age, body mass index, diabetes mellitus, supine mean arterial pressure, number of drugs taken per day, use of antihypertensive or psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol consumption, serum concentrations of parathyroid hormone, calcium and creatinine and season of testing. Diastolic orthostatic hypotension was observed more often among women with vitamin D deficiency (19.2%) compared to those without (10.0%; P = 0.03). There was an inverse linear association between 25OHD concentration and change in diastolic blood pressure after 3 min of standing (adjusted β = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004], specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P = 0.003). 25OHD deficiency was associated with orthostatic hypotension in oldest-old women, due to a greater drop in diastolic blood pressure on standing. This finding may lead to better understanding of the pathophysiology of falls in oldest-old adults with vitamin D deficiency. © 2014 The Association for the Publication of the Journal of

Randomized Withdrawal Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension Responsive to Droxidopa

PubMed Central

Freeman, Roy; Mathias, Christopher J.; Low, Phillip; Hewitt, L. Arthur; Kaufmann, Horacio

2015-01-01

Abstract— We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100–600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient’s self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. Clinical Trial Registration— URL: http

Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa.

PubMed

Biaggioni, Italo; Freeman, Roy; Mathias, Christopher J; Low, Phillip; Hewitt, L Arthur; Kaufmann, Horacio

2015-01-01

We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100-600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient's self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. http://www.clinicaltrials.gov. Unique identifier: NCT00633880

Orthostatic Hypotension: Mechanisms, Causes, Management

PubMed Central

Tomalia, Victoria A.

2015-01-01

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson's disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH. PMID:26174784

L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience.

PubMed

Kaufmann, Horacio

2008-03-01

Neurogenic orthostatic hypotension results from failure to release norepinephrine, the neurotransmitter of sympathetic postganglionic neurons, appropriately upon standing. In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme L: -aromatic amino acid decarboxylase increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability in patients with neurogenic orthostatic hypotension due to degenerative autonomic disorders. The pressor effect results from conversion of droxidopa to norepinephrine outside the central nervous system both in neural and non-neural tissue. This mechanism of action makes droxidopa effective in patients with central and peripheral autonomic disorders.

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

NASA Technical Reports Server (NTRS)

Jankovic, J.; Gilden, J. L.; Hiner, B. C.; Kaufmann, H.; Brown, D. C.; Coghlan, C. H.; Rubin, M.; Fouad-Tarazi, F. M.

1993-01-01

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Orthostatic hypotension and overall mortality in 1050 older patients of the outpatient comprehensive geriatric assessment unit.

PubMed

Freud, Tamar; Punchik, Boris; Kagan, Ella; Barzak, Alex; Press, Yan

2018-03-02

Orthostatic hypotension is a common problem in individuals aged ≥65 years. Its association with mortality is not clear. The aim of the present study was to evaluate associations between orthostatic hypotension and overall mortality in a sample of individuals aged ≥65 years who were seen at the Outpatient Comprehensive Geriatric Assessment Unit, Clalit Health Services, Beer-Sheva, Israel. Individuals who were evaluated in the Outpatient Comprehensive Geriatric Assessment Unit between January 2005 and December 2015, and who had data on orthostatic hypotension were included in the study. The database included sociodemographic characteristics, body mass index, functional and cognitive state, geriatric syndromes reached over the course of the assessment, and comorbidity. Data on mortality were also collected. The study sample included 1050 people, of whom 626 underwent comprehensive geriatric assessment and 424 underwent geriatric consultation. The mean age was 77.3 ± 5.4 years and 35.7% were men. Orthostatic hypotension was diagnosed in 294 patients (28.0%). In univariate analysis, orthostatic hypotension was associated with overall mortality only in patients aged 65-75 years (HR 1.5, 95% CI 1.07-2.2), but in the multivariate model this association disappeared. In older frail patients, orthostatic hypotension was not an independent risk factor for overall mortality. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 Japan Geriatrics Society.

Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report.

PubMed

Hale, Genevieve M; Brenner, Michael

2015-09-01

Several nonpharmacologic strategies for orthostatic hypotension exist including avoiding large carbohydrate-rich meals; limiting alcohol consumption; maintaining adequate hydration; adding salt to foods; and using compression stockings, tilt-table exercises, or abdominal binders. If these fail, however, only limited evidence-based pharmacologic treatment options are available including the use of fludrocortisone, midodrine, pyridostigmine, and droxidopa as well as pseudoephedrine, ocetreotide, and atomoxetine. This report discusses a case of atomoxetine use for 10 weeks in an elderly patient with primary orthostatic hypotension. An 84-year-old man with long-standing primary orthostatic hypotension presented to our ambulatory cardiology pharmacotherapy clinic after several unsuccessful pharmacologic therapies including fludrocortisone, midodrine, and pyridostigmine. Nonpharmacologic strategies were also implemented. Atomoxetine was initiated, and the patient showed gradual improvements in symptoms and blood pressure control over the course of 10 weeks. Our data suggest that low-dose atomoxetine is an effective and safe agent for symptom improvement and blood pressure control in elderly patients with primary orthostatic hypotension. © 2015 Pharmacotherapy Publications, Inc.

Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.

PubMed

Moonen, Justine E F; Foster-Dingley, Jessica C; de Ruijter, Wouter; van der Grond, Jeroen; de Craen, Anton J M; van der Mast, Roos C

2016-03-01

the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials. to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment. a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses. at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]. in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension. © The Author 2016. Published by Oxford

Fludrocortisone does not prevent orthostatic hypotension in astronauts after spaceflight.

PubMed

Shi, Shang-Jin; South, Donna A; Meck, Janice V

2004-03-01

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. 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. 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. 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.

Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension

NASA Technical Reports Server (NTRS)

Fujimura, J.; Camilleri, M.; Low, P. A.; Novak, V.; Novak, P.; Opfer-Gehrking, T. L.

1997-01-01

Our aims were to evaluate to role of superior mesenteric blood flow in the pathophysiology of orthostatic hypotension in patients with generalized autonomic failure. METHODS: Twelve patients with symptomatic neurogenic orthostatic hypotension and 12 healthy controls underwent superior mesenteric artery flow measurements using Doppler ultrasonography during head-up tilt and tilt plus meal ingestion. Autonomic failure was assessed using standard tests of the function of the sympathetic adrenergic, cardiovagal and postganglionic sympathetic sudomotor function. RESULTS: Superior mesenteric flow volume and time-averaged velocity were similar in patients and controls at supine rest; however, responses to cold pressor test and upright tilt were attenuated (p < 0.05) in patients compared to controls. Head-up tilt after the meal evoked a profound fall of blood pressure and mesenteric blood flow in the patients; the reduction of mesenteric blood flow correlated (r = 0.89) with the fall of blood pressure in these patients, providing another manifestation of failed baroreflexes. We make the novel finding that the severity of postprandial orthostatic hypotension regressed negatively with the postprandial increase in mesenteric flow in patients with orthostatic hypotension. CONCLUSION: Mesenteric flow is under baroreflex control, which when defective, results in, or worsens orthostatic hypotension. Its large size and baroreflexivity renders it quantitatively important in the maintenance of postural normotension. The effects of orthostatic stress can be significantly attenuated by reducing the splanchnic-mesenteric volume increase in response to food. Evaluation of mesenteric flow in response to eating and head-up tilt provide important information on intra-abdominal sympathetic adrenergic function, and the ability of the patient to cope with orthostatic stress.

Effectiveness of droxidopa compared to midodrine in standing blood pressure and orthostatic tolerance in adults with neurogenic orthostatic hypotension: a systematic review protocol.

PubMed

Patrick, Kelli; Martin, Tina

2017-09-01

The question of this review is: what is the effectiveness of droxidopa compared to midodrine on standing blood pressure and orthostatic intolerance symptoms in adults with neurogenic orthostatic hypotension?

Recent advances in orthostatic hypotension presenting orthostatic dizziness or vertigo.

PubMed

Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

2015-11-01

Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is known to be the most common symptom of OH. However, recent studies have demonstrated that 30-39 % of patients with OH experienced rotatory vertigo during upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that OH induces dizziness and not vertigo. A recent population-based study on spontaneously occurring OD across a wide age range showed that the one-year and lifetime prevalence of OD was 10.9 and 12.5 %, respectively. Approximately 83 % of patients with OD had at least one abnormal autonomic function test result. So far, 11 subtypes of OD have been proposed according to the pattern of autonomic dysfunction, and generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions was the most common type. Four different patterns of OH, such as classic, delayed, early, and transient type have been found in patients with OD. The head-up tilt test and Valsalva maneuver should be performed for a comprehensive evaluation of sympathetic adrenergic failure in patients with OD/OV. This review summarizes current advances in OH presenting OD/OV, with a particular focus on the autonomic dysfunction associated with OD.

Bed Rest and Orthostatic-Hypotensive Intolerance

NASA Technical Reports Server (NTRS)

Schneider, Suzanne M.

2000-01-01

Orthostatic tolerance may be defined as the ability of humans to maintain cerebral perfusion and consciousness upon movement from a supine or sitting position to the upright posture; for example, subjects can stand suddenly or be tilted to the head-up body position. Similar but not identical physiological responses can be induced by positive G(sub Z) (head to foot) acceleration or exposure to lower body negative pressure (LBNP). The objective is to suddenly shift blood to the lower body to determine how effectively cardiovascular and neural-hormonal compensatory responses react to maintain blood pressure. In the most precise method for measuring tolerance, individuals would be stressed until they faint (syncope). However, the potential consequences and discomforts of such a test usually prohibit such a procedure so that few investigators actually induce syncope. In a more common approach, subjects are exposed to a given level of stress, for example, head-up tilt for 15 min, and any increases in heart rate or decreases in blood pressure are interpreted as indicators of progress toward syncope. Presumably, the greater the perturbation of heart rate and blood pressure, the closer to "tolerance," i.e., point of unconsciousness. Another more appropriate approach is to induce a progressively increasing hypotensive stress until pre-determined physiological responses or pre-syncopal symptoms appear. The physiological criteria may include a sudden drop in systolic blood pressure (greater than 25 mm/min), a sudden drop in heart rate (greater than 15 beats/min), or a systolic blood pressure less than 70 mmHg. The most common pre-syncopal symptoms include lightheadedness, stomach awareness or distress, feelings of warmth, tingly skin, and light to profuse sweating. Usually a combination of physiological responses and symptoms occurs such that, on different days, the tolerance time to the same orthostatic protocol is reproducible for a given individual. The assumption is that

Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure.

PubMed

Ramirez, Claudia E; Okamoto, Luis E; Arnold, Amy C; Gamboa, Alfredo; Diedrich, André; Choi, Leena; Raj, Satish R; Robertson, David; Biaggioni, Italo; Shibao, Cyndya A

2014-12-01

The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure. © 2014 American Heart Association, Inc.

Droxidopa for orthostatic hypotension: a systematic review and meta-analysis.

PubMed

Strassheim, Victoria; Newton, Julia L; Tan, Maw Pin; Frith, James

2016-10-01

The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States. MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis. Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)]. Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension. PROSPERO ID CRD42015024612.

Patients' choice of portable folding chairs to reduce symptoms of orthostatic hypotension

NASA Technical Reports Server (NTRS)

Smit, A. A.; Wieling, W.; Opfer-Gehrking, T. L.; van Emmerik-Levelt, H. M.; Low, P. A.

1999-01-01

Patients with neurogenic orthostatic hypotension may use portable folding chairs to prevent or reduce symptoms of low blood pressure. However, a concomitant movement disorder may limit the use of these chairs in daily living. In this prospective study, 13 patients with orthostatic hypotension, balance disturbance associated with motor disability, or both examined three commercially available portable folding chairs. A questionnaire was used to document the characteristics in chair design that were relevant for satisfactory use to these patients. Armrests, seat width, and an adjustable sitting height were found to be important features of a portable folding chair. One chair was selected by 11 of 13 patients to fit most needs.

Diagnosing and treating neurogenic orthostatic hypotension in primary care.

PubMed

Kuritzky, Louis; Espay, Alberto J; Gelblum, Jeffrey; Payne, Richard; Dietrich, Eric

2015-01-01

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient's risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension - for which the long-term prognosis in patients with NOH is yet to be established - must sometimes be balanced by the need to address a patient's immediate risks.

Hypovolemia-induced Orthostatic Hypotension Relates To Hypo-sympathetic Responsiveness

NASA Technical Reports Server (NTRS)

Meck, Janice V.

2007-01-01

We report a new model which uses hypovolemia to force humans into a hemodynamic state that is similar to that after spaceflight. This model can be used to test candidate countermeasures for postflight orthostatic hypotension and to identify crewmembers who will be most susceptible to that symptom on landing day.

Does training-induced orthostatic hypotension result from reduced carotid baroreflex responsiveness?

NASA Technical Reports Server (NTRS)

Pawelczyk, James A.; Raven, Peter B.

1994-01-01

As manned space travel has steadily increased in duration and sophistication, the answer to a simple, relevant question remains elusive. Does endurance exercise training - high intensity rhythmic activity, performed regularly for extended periods of time - alter the disposition to, or severity of, postflight orthostatic hypotension? Research results continue to provide different views; however, data are difficult to compare because of the following factors that vary between investigations: the type of orthostatic stress imposed (+Gz, lower body negative pressure (LBNP), head-up tilt); pretest perturbations used (exercise, heat exposure, head-down tilting, bed rest, water immersion, hypohydration, pharmacologically-induced diuresis); the length of the training program used in longitudinal investigations (days versus weeks versus months); the criteria used to define fitness; and the criteria used to define orthostatic tolerance. Generally, research results indicate that individuals engaged in aerobic exercise activities for a period of years have been reported to have reduced orthostatic tolerance compared to untrained control subjects, while the results of shorter term longitudinal studies remain equivocal. Such conclusions suggest that chronic athletic training programs reduce orthostatic tolerance, whereas relatively brief (days to weeks) training programs do not affect orthostatic tolerance to any significant degree (increase or decrease). A primary objective was established to identify the alterations in blood pressure control that contribute to training-induced orthostatic hypotension (TIOH). Although any aspect of blood pressure regulation is suspect, current research has been focused on the baroreceptor system. Reductions in carotid baroreflex responsiveness have been documented in exercise-trained rabbits, reportedly due to an inhibitory influence from cardiac afferent, presumably vagal, nerve fibers that is abolished with intrapericardiac denervation. The

New developments in the management of neurogenic orthostatic hypotension.

PubMed

Biaggioni, Italo

2014-11-01

Orthostatic hypotension (OH) is defined as a sustained reduction of ≥ 20 mmHg systolic blood pressure or ≥ 10 mmHg diastolic blood pressure upon standing for ≤ 3 min. Orthostatic hypotension is commonly associated with hypertension, and its prevalence is highest in those with uncontrolled hypertension compared to those with controlled hypertension or normotensive community elderly subjects. Orthostatic hypotension can cause significant disability, with patients experiencing dizziness, lightheadedness or syncope, and other problems that potentially have a profound negative impact on activities of daily living that require standing or walking. Furthermore, OH increases the risk of falls and, importantly, is an independent risk factor of mortality. Despite its importance, there is a paucity of treatment options for this condition. Most of the advances in treatment options have relied on small studies of repurposed drugs done in patients with severe OH due to rare neurodegenerative conditions. Midodrine, an oral prodrug converted to the selective α1-adrenoceptor agonist desglymidodrine, was approved by the FDA for the treatment of OH in 1996. For almost two decades, no other pharmacotherapy was developed specifically for the treatment of OH until 2014, when droxidopa was approved by the FDA for the treatment of neurogenic OH associated with primary autonomic neuropathies including Parkinson disease, multiple system atrophy, and pure autonomic failure. These are neurodegenerative diseases ultimately characterized by failure of the autonomic nervous system to generate norepinephrine responses appropriate to postural challenge. Droxidopa is a synthetic amino acid that is converted to norepinephrine by dopa-decarboxylase, the same enzyme that converts levodopa into dopamine in the treatment of Parkinson disease. We will review this and other advances in the treatment of OH in an attempt to provide a practical guide to its management.

Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.

PubMed

Kurihara, J; Takata, Y; Suzuki, S; Okubo, Y; Kato, H

2000-12-01

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.

Idiopathic orthostatic intolerance and postural tachycardia syndromes

NASA Technical Reports Server (NTRS)

Jacob, G.; Biaggioni, I.; Robertson, D. (Principal Investigator)

1999-01-01

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.

Orthostatic Hypotension: Epidemiology, Prognosis, and Treatment.

PubMed

Ricci, Fabrizio; De Caterina, Raffaele; Fedorowski, Artur

2015-08-18

Orthostatic hypotension (OH) is a common cardiovascular disorder, with or without signs of underlying neurodegenerative disease. OH is diagnosed on the basis of an orthostatic challenge and implies a persistent systolic/diastolic blood pressure decrease of at least 20/10 mm Hg upon standing. Its prevalence is age dependent, ranging from 5% in patients <50 years of age to 30% in those >70 years of age. OH may complicate treatment of hypertension, heart failure, and coronary heart disease; cause disabling symptoms, faints, and traumatic injuries; and substantially reduce quality of life. Despite being largely asymptomatic or with minimal symptoms, the presence of OH independently increases mortality and the incidence of myocardial infarction, stroke, heart failure, and atrial fibrillation. In this review, we outline the etiology and prevalence of OH in the general population, summarize its relationship with morbidity and mortality, propose a diagnostic and therapeutic algorithm, and delineate current challenges and future perspectives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension.

PubMed

Hauser, Robert A; Heritier, Stephane; Rowse, Gerald J; Hewitt, L Arthur; Isaacson, Stuart H

2016-01-01

Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed.

Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension

PubMed Central

Hauser, Robert A.; Heritier, Stephane; Rowse, Gerald J.; Hewitt, L. Arthur; Isaacson, Stuart H.

2016-01-01

Objectives Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Methods Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. Results A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Conclusions Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed. PMID:27332626

Norepinephrine precursor therapy in neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Saadia, Daniela; Voustianiouk, Andrei; Goldstein, David S; Holmes, Courtney; Yahr, Melvin D; Nardin, Rachel; Freeman, Roy

2003-08-12

In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture. We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L-aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH (8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine (from 101+/-4 to 141+/-5 mm Hg) and standing (from 60+/-4 to 100+/-6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patients Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.

Graded Compression Stockings Prevent Post-spaceflight Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, S. H.; Brown, A. K.; Locke, J.; Stenger, M. B.

2008-01-01

Post-spaceflight orthostatic intolerance is characterized by hypotension and presyncope in 20-30% of returning 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, which are typically pressurized from 0.5 to 1.5 PSI (27 to 78 mmHg). ISS crew members sometimes wear Russian Kentavr suits which consist of laced compression shorts and gaiters, providing 30 mmHg nominally. While these garments are effective during reentry, there are a number of drawbacks that make them impractical for postflight use. We studied the ability of commercially available, custom fit, graded compression stockings (Jobst, 55 mmHg at ankle to 6 mmHg at top of thigh, 25 mmHg mean compression) to prevent postflight orthostatic intolerance, hypothesizing that these garments would prevent orthostatic intolerance following short duration space flight. Crew members from a single Space Shuttle flight were tilted to 80 degrees for 10 min while wearing the stockings (n=5 males) upon arrival at the clinic (2 hrs after landing). Hemodynamic data were compared to data from all crewmembers tilted (without countermeasures) since return to flight (n=9). Two-way, repeated measures ANOVA, using the entire tilt time curve (0-10 min) show that systolic blood pressure (SBP, group effect p=0.008), stroke volume (SV, group effect p=0.003), and cardiac output (CO, group effect p=0.004) were higher in crewmembers who wore the Jobst stockings. A one-way ANOVA comparing the last minute standing also showed that SV (p=0.001) and CO (p less than 0.001) were higher and SBP tended to be higher (p=0.06) in Jobst subjects compared to controls. Control subjects had a higher rate of presyncope than Jobst subjects (3/9 vs 0/5) during the tilt on landing day. Orthostatic hypotension continues to present following spaceflight, despite

Droxidopa for neurogenic orthostatic hypotension

PubMed Central

Freeman, Roy; Biaggioni, Italo; Low, Phillip; Pedder, Simon; Hewitt, L. Arthur; Mauney, Joe; Feirtag, Michael; Mathias, Christopher J.

2014-01-01

Objective: To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Methods: Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100–600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. Results: From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in “dizziness/lightheadedness.” Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for “standing a long time.” Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. Conclusions: In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. Classification of evidence: This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days. PMID:24944260

Droxidopa in neurogenic orthostatic hypotension

PubMed Central

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

2015-01-01

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy, pure autonomic failure and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise blood pressure by acting at the neurovascular junction to increase vascular tone. This review summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

Droxidopa in neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

2015-01-01

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy (MSA), pure autonomic failure (PAF), and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials.

Long-Lasting Orthostatic Hypotension and Constipation After Celiac Plexus Block; A Case Report.

PubMed

Yousefshahi, Fardin; Tahmasebi, Mamak

2018-02-01

This case report presents a 55 years old man, presented with abdominal pain and diagnosed with a metastatic pancreatic tumor, who developed long lasting orthostatic hypotension and constipation following a celiac plexus block.

Orthostatic hypotension: pathophysiology, assessment, treatment and the paradox of supine hypertension.

PubMed

Chisholm, Peter; Anpalahan, Mahesan

2017-04-01

Both hypertension and orthostatic hypotension (OH) are strongly age-associated and are common management problems in older people. However, unlike hypertension, management of OH has unique challenges with few well-established treatments. Not infrequently, they both coexist, further compounding the management. This review provides comprehensive information on OH, including pathophysiology, diagnostic workup and treatment, with a view to provide a practical guide to its management. Special references are made to patients with supine hypertension and postprandial hypotension and older hypertensive patients. © 2016 Royal Australasian College of Physicians.

Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

Isaacson, Stuart; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J; Kalu, Uwa; White, William B

2016-10-01

The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Long-Lasting Orthostatic Hypotension and Constipation After Celiac Plexus Block; A Case Report

PubMed Central

Yousefshahi, Fardin; Tahmasebi, Mamak

2018-01-01

This case report presents a 55 years old man, presented with abdominal pain and diagnosed with a metastatic pancreatic tumor, who developed long lasting orthostatic hypotension and constipation following a celiac plexus block. PMID:29868459

Recurrent syncope, orthostatic hypotension and volatile hypertension: think outside the box.

PubMed

Aung, Thein; Fan, Wuqiang; Krishnamurthy, Mahesh

2013-01-01

The baroreceptors in the neck and aortic arch are important regulators of sudden blood pressure changes. They are innervated by CN IX and X and synapse in the brainstem. Baroreceptor failure is an under-recognized cause of recurrent syncope, orthostatic hypotension, and volatile hypertension, which is refractory to and may in fact worsen with conventional treatments. Baroreflex failure can be the result of neck and chest radiation, head and neck surgery, and cerebrovascular accidents involving the brainstem nuclei. The management of baroreflex failure is a challenge since patient education, lifestyle changes, and family support are extremely important in managing blood pressure. Leg exercises and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating orthostatic hypotension. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest. Temporal relationship between symptoms onset and the history of head, neck, and upper chest radiation or trauma is important in reaching a diagnosis.

Hemodynamic Effects of Midodrine After Space Flight in Astronauts Without Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Ziegler, Michael G.; Waters, Wendy W.; Meck, Janice V.

2006-01-01

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 -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. Five male astronauts participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing, approximately 1 hour before testing. 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). 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.

Role of physical countermaneuvers in the management of orthostatic hypotension: efficacy and biofeedback augmentation

NASA Technical Reports Server (NTRS)

Bouvette, C. M.; McPhee, B. R.; Opfer-Gehrking, T. L.; Low, P. A.

1996-01-01

OBJECTIVE: To evaluate the efficacy of various physical countermaneuvers in reducing orthostatic hypotension and its associated symptoms and to assess the efficacy of biofeedback training in enhancing the effectiveness of physical countermaneuvers. MATERIAL AND METHODS: In nine study subjects with neurogenic orthostatic hypotension, four training sessions on physical countermaneuvers were performed after tilt-up, three with visual feedback on the effect of physical countermaneuvers on blood pressure and other cardiovascular variables. Blood pressure change and orthostatic symptoms during tilt-up were determined, as were the changes in total peripheral resistance, stroke index, and heart rate. RESULTS: The five female and four male patients had a mean age of 53 years and a mean duration of symptoms of 4.2 years. On an orthostatic symptom scale of 0 to 10, these patients had a mean symptom score of 7.3. The increment in systolic blood pressure was better for some maneuvers (such as leg crossing and a combination) than others (such as neck flexion and abdominal contraction). Three patterns of responses to biofeedback were found. Simple maneuvers such as squatting did not improve with training; visual feedback was needed for maneuvers such as thigh contraction, and performance declined without biofeedback; the third pattern, seen in maneuvers such as leg crossing, showed continued improvement with training, even without biofeedback. A survey at 3 to 4 months after training revealed continued use of physical maneuvers (3.8 +/- 3.1 per day), increased standing time with each episode of presyncopal symptoms (8.3 +/- 5.8 minutes), and continued global symptomatic improvement. Total peripheral resistance, but not heart rate or stroke index, showed significant regression with blood pressure improvement. CONCLUSION: Physical countermaneuvers are efficacious in reducing orthostatic hypotension, can be augmented by use of biofeedback, and may significantly improve the

Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia.

PubMed

Tutaj, Marcin; Marthol, Harald; Berlin, Dena; Brown, Clive M; Axelrod, Felicia B; Hilz, Max J

2006-01-01

Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension, we evaluated the effectiveness of countermaneuvers in FD patients. In 17 FD patients (26.4 +/- 12.4 years, eight female), we monitored heart rate (HR), blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume while supine, during standing and during application of four countermaneuvers: bending forward, squatting, leg crossing, and abdominal compression using an inflatable belt. Countermaneuvers were initiated after standing up,when systolic BP had fallen by 40mmHg or diastolic BP by 30mmHg or presyncope had occurred. During active standing, blood pressure and TPR decreased, calf volume increased but CO remained stable. Mean BP increased significantly during bending forward (by 20.0 (17 - 28.5) mmHg; P = 0.005) (median (25(th) - 75(th) quartile)), squatting (by 50.8 (33.5 - 56) mmHg; P = 0.002), and abdominal compression (by 5.8 (-1 - 34.7) mmHg; P = 0.04) - but not during leg-crossing. Squatting and abdominal compression also induced a significant increase in CO (by 18.1 (-1.3 - 47.9) % during squatting (P = 0.02) and by 7.6 (0.4 - 19.6) % during abdominal compression (P=0.014)). HR did not change significantly during the countermaneuvers. TPR increased significantly only during squatting (by 37.2 (11.8 - 48.2) %; P = 0.01). However, orthopedic problems or ataxia prevented several patients from performing some of the countermaneuvers. Additionally, many patients required assistance with the maneuvers. Squatting, bending forward and abdominal compression can improve orthostatic BP in FD patients, which is achieved mainly by an increased cardiac output. Squatting has the greatest effect on orthostatic blood pressure in FD patients. Suitability and effectiveness of a specific countermaneuver depends on the orthopedic

A review of the etiology, associated comorbidities, and treatment of orthostatic hypotension.

PubMed

Perlmuter, Lawrence C; Sarda, Garima; Casavant, Vanessa; Mosnaim, Aron D

2013-01-01

The magnitude of increase in systolic blood pressure in response to the shift from supine to upright posture is considered to reflect the adequacy of orthostatic regulation. Orthostatic integrity is largely maintained by the interaction between the skeletal muscle pump, neurovascular compensation, neurohumoral effects, and cerebral blood flow regulation. Various physiological states and disease conditions may disrupt these mechanisms as seen in vasovagal syncope, dysautonomic orthostatic intolerance, and postural orthostatic tachycardia syndrome. Orthostatic hypotension (OH) and decreased cerebral blood flow are strongly related. Even subclinical OH has been associated to different degrees with impaired cognitive function, decreased effort, reduced motivation, increased hopelessness, and signs of attention-deficit hyperactivity disorder and dementia, diabetes mellitus, and Parkinson disease. Furthermore, subclinical levels of inadequate blood pressure regulation in response to orthostasis have been linked to increased depression and anxiety and intergenerational behavioral sequelae between mother and child. Identifying causes of subclinical and clinical OH is critical in improving quality of life for both children and older adults. A better understanding of the underlying causes responsible for the etiology of OH could lead to a rational design of novel effective therapeutic regimens for the treatment of this condition and associated comorbidities.

Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension.

PubMed

Belz, G G; Butzer, R; Gaus, W; Loew, D

2002-10-01

In order to test the efficacy of a combination of natural D-camphor and an extract of fresh crataegus berries (Korodin Herz-Kreislauf-Tropfen) on orthostatic hypotension, two similar, controlled, randomized studies were carried out in a balanced crossover design in 24 patients each with orthostatic dysregulation. The camphor-crataegus berry combination (CCC) was orally administered as a single regimen in 3 different dosages of 5 drops, 20 drops and 80 drops; a placebo with 20 drops of a 60% alcoholic solution served as control. Orthostatic hypotension was assessed with the tilt table test before and after medication. Source data of both studies were pooled and meta-analytically evaluated for all 48 patients. CCC drops decreased the orthostatic fall in blood pressure versus placebo, as almost uniformly established at all times by mean arterial pressure and diastolic blood pressure. Mean arterial pressure demonstrated the very fast onset of action by a clearly dose-dependent statistically significant effect even after 1-minute orthostasis. Increase of mean arterial pressure as compared to the orthostasis test before medication was on average 4.5 mmHg. CCC affected diastolic blood pressure after 1 minute of orthostasis in all dosages as compared to placebo. A statistically significant effect of the highest dose of 80 drops on diastolic blood pressure could be demonstrated after 1-, 3-, and 5-minute orthostasis. The hemodynamic findings of a stabilizing effect on arterial pressure in orthostasis corroborate the long-term medical experience with CCC and justify the indication orthostatic hypotension.

Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension.

PubMed

Byun, Jung-Ick; Moon, Jangsup; Kim, Do-Yong; Shin, Hyerim; Sunwoo, Jun-Sang; Lim, Jung-Ah; Kim, Tae-Joon; Lee, Woo-Jin; Lee, Han Sang; Jun, Jin-Sun; Park, Kyung-Il; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Lee, Sang Kun; Chu, Kon

2017-09-05

To evaluate the long-term (for up to 3 months) efficacy and safety of single or combined therapy with midodrine and pyridostigmine for neurogenic orthostatic hypotension (OH). This was a randomized, open-label clinical trial. In total, 87 patients with symptomatic neurogenic OH were enrolled and randomized to receive 1 of 3 treatments: midodrine only, pyridostigmine only, or midodrine + pyridostigmine. The patients were followed up at 1 and 3 months after treatment. The primary outcome measures were improvement in orthostatic blood pressure (BP) drop at 3 months. Secondary endpoints were improvement of the orthostatic BP drop at 1 month and amelioration of the questionnaire score evaluating OH-associated symptoms. Orthostatic systolic and diastolic BP drops improved significantly at 3 months after treatment in all treatment groups. Orthostatic symptoms were significantly ameliorated during the 3-month treatment, and the symptom severity was as follows: midodrine only < midodrine + pyridostigmine < pyridostigmine only group. Mild to moderate adverse events were reported by 11.5% of the patients. Single or combination treatment with midodrine and pyridostigmine was effective and safe in patients with OH for up to 3 months. Midodrine was better than pyridostigmine at improving OH-related symptoms. NCT02308124. This study provides Class IV evidence that for patients with neurogenic OH, long-term treatment with midodrine alone, pyridostigmine alone, or both midodrine and pyridostigmine is safe and has similar effects in improving orthostatic BP drop up to 3 months. © 2017 American Academy of Neurology.

Agonistic autoantibodies as vasodilators in orthostatic hypotension: a new mechanism.

PubMed

Li, Hongliang; Kem, David C; Reim, Sean; Khan, Muneer; Vanderlinde-Wood, Megan; Zillner, Caitlin; Collier, Daniel; Liles, Campbell; Hill, Michael A; Cunningham, Madeleine W; Aston, Christopher E; Yu, Xichun

2012-02-01

Agonistic autoantibodies to the β-adrenergic and muscarinic receptors are a novel investigative and therapeutic target for certain orthostatic disorders. We have identified the presence of autoantibodies to β2-adrenergic and/or M3 muscarinic receptors by ELISA in 75% (15 of 20) of patients with significant orthostatic hypotension. Purified serum IgG from all 20 of the patients and 10 healthy control subjects were examined in a receptor-transfected cell-based cAMP assay for β2 receptor activation and β-arrestin assay for M3 receptor activation. There was a significant increase in IgG-induced activation of β2 and M3 receptors in the patient group compared with controls. A dose response was observed for both IgG activation of β2 and M3 receptors and inhibition of their activation with the nonselective β blocker propranolol and muscarinic blocker atropine. The antibody effects on β2 and/or M3 (via production of NO) receptor-mediated vasodilation were studied in a rat cremaster resistance arteriole assay. Infusion of IgG from patients with documented β2 and/or M3 receptor agonistic activity produced a dose-dependent vasodilation. Sequential addition of the β-blocker propranolol and the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester partially inhibited IgG-induced vasodilation (percentage of maximal dilatory response: from 57.7±10.4 to 35.3±4.6 and 24.3±5.8, respectively; P<0.01; n=3), indicating that antibody activation of vascular β2 and/or M3 receptors may contribute to systemic vasodilation. These data support the concept that circulating agonistic autoantibodies serve as vasodilators and may cause or exacerbate orthostatic hypotension.

Evidence for vestibular dysfunction in orthostatic hypotension.

PubMed

Aoki, Mitsuhiro; Sakaida, Yuzuru; Tanaka, Kunihiko; Mizuta, Keisuke; Ito, Yatsuji

2012-03-01

There is little definitive evidence of the clinical significance of the vestibular-cardiovascular reflex in humans, despite the fact that the vestibular system is known to contribute to cardiovascular control in animals. The present study involved 248 dizzy patients (127 male patients and 121 female patients) aged 65 years and younger. We classified all participants into three groups based on their vestibular evoked myogenic potential (VEMP) responses; absent VEMP, asymmetry VEMP and normal VEMP. To investigate the effect of the otolith disorder, which was estimated by the VEMP, on the orthostatic blood pressure responses, the subjects' systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were monitored during the orthostatic test after they actively stood up. The male patients in the absent VEMP group had a significant drop in their DBP at 1 min after active standing up (P < 0.05) without any change in their SBP. Conversely, male patients in the asymmetry VEMP and normal VEMP groups showed a significant increase in the SBP at 1 min after active standing up (P < 0.05). Female patients in the absent VEMP group did not show any significant drop in their blood pressure after standing up (P > 0.05). In the entire group of participants, a total of 19.6% of the patients in the absent VEMP group fulfilled the criteria for orthostatic hypotension (OH), which was significantly > the 8.6% of patients in the normal VEMP group and the 7.2% in the asymmetry VEMP group (P < 0.05). Our results suggest that vestibular disorders due to the dysfunction of otolith organs provoke OH.

Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension.

PubMed

Elgebaly, Ahmed; Abdelazeim, Bassant; Mattar, Omar; Gadelkarim, Mohamed; Salah, Rehab; Negida, Ahmed

2016-06-01

Droxidopa has been approved for the treatment of neurogenic orthostatic hypotension (NOH) under the US Food and Drug Administration accelerated approval program, which warrants confirmatory evidence on long-term efficacy of droxidopa. Hereby, we synthesize evidence from published randomized controlled trials (RCTs) about the safety and efficacy of droxidopa for patients with neurogenic orthostatic hypotension. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 5.3 for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate long-term durability of droxidopa against placebo. Four RCTs with a total of 485 patients (droxidopa, n = 246; placebo, n = 239) were eligible for the final analysis. The mean difference (MD) of change in the main outcomes from baseline to endpoint favored droxidopa than placebo [Orthostatic Hypotension Questionnaire (OHQ) MD -0.61, P = 0.004; dizziness/lightheadedness score MD -0.83, P = 0.008; and standing systolic blood pressure (SBP) MD 4.09, P = 0.03]. The efficacy of droxidopa decreased gradually after 2 weeks, and its statistical significance was lost after 8 weeks (OHQ score MD -0.18, P = 0.61; dizziness/lightheadedness score MD -0.71, P = 0.11; and standing SBP MD 2.96, P = 0.29). None of the adverse events were significantly higher in the case of droxidopa compared to placebo. Droxidopa is a safe and effective drug for the short-term management of NOH symptoms. However, current evidence is insufficient to confirm the efficacy of droxidopa for long-term use. Therefore, further studies with increased sample size are needed.

The Treatment of Primary Orthostatic Hypotension.

PubMed

Hale, Genevieve M; Valdes, Jose; Brenner, Michael

2017-05-01

To review the efficacy and safety of pharmacological and nonpharmacological strategies used to treat primary orthostatic hypotension (OH). A literature review using PubMed and MEDLINE databases searching hypotension, non-pharmacological therapy, midodrine, droxidopa, pyridostigmine, fludrocortisone, atomoxetine, pseudoephedrine, and octreotide was performed. Randomized or observational studies, cohorts, case series, or case reports written in English between January 1970 and November 2016 that assessed primary OH treatment in adult patients were evaluated. Based on the chosen criteria, it was found that OH patients make up approximately 15% of all syncope patients, predominantly as a result of cardiovascular or neurological insults, or offending medication. Nonpharmacological strategies are the primary treatment, such as discontinuing offending medications, switching medication administration to bedtime, avoiding large carbohydrate-rich meals, limiting alcohol, maintaining adequate hydration, adding salt to diet, and so on. If these fail, pharmacotherapy can help ameliorate symptoms, including midodrine, droxidopa, fludrocortisone, pyridostigmine, atomoxetine, sympathomimetic agents, and octreotide. Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms. Pyridostigmine and fludrocortisone can be used in patients who fail to respond to these agents. Emerging evidence with low-dose atomoxetine is promising, especially in those with central autonomic failure, and may prove to be a viable alternative treatment option. Data surrounding other therapies such as sympathomimetic agents or octreotide are minimal. Medication management of primary OH should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions.

Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure.

PubMed

Shibao, Cyndya; Okamoto, Luis E; Gamboa, Alfredo; Yu, Chang; Diedrich, Andre'; Raj, Satish R; Robertson, David; Biaggioni, Italo

2010-11-01

Orthostatic hypotension affects patients with autonomic failure producing considerable disability because of presyncopal symptoms. Severely affected patients may have residual sympathetic tone that can be engaged to increase blood pressure (BP) with the α-2 adrenergic antagonist yohimbine. This medication activates sympathetic outflow centrally and unrestrains norepinephrine release from noradrenergic neurons. Alternatively, the acetylcholinesterase inhibitor, pyridostigmine, can increase sympathetic tone by improving ganglionic cholinergic neurotransmission. Our purpose was to compare these complementary approaches and to explore whether the combination would lead to synergistic increases in BP. We compared the effects of 60 mg of pyridostigmine and 5.4 mg of yohimbine in a single-blind, randomized, placebo-controlled, crossover fashion. In a subset of patients we tested the combination of pyridostigmine and yohimbine. Our primary outcome was the change in standing diastolic BP 60 minutes after drug administration from baseline. We studied a total of 31 patients with severe autonomic failure. Yohimbine significantly improved standing diastolic BP as compared with placebo (11±3 mm Hg [95% CI: 6 to 16 mm Hg]; P<0.001). On the contrary, pyridostigmine did not increase the standing diastolic BP (0.6±3 mm Hg [95% CI: -5 to 5 mm Hg]; P=0.823). Only yohimbine showed a significant improvement in presyncopal symptoms. Sixteen patients received the combination of pyridostigmine and yohimbine, but no evidence of synergistic pressor effect was found. Engaging residual sympathetic tone with yohimbine is a more effective approach to improve orthostatic hypotension as compared with pyridostigmine in patients with severe orthostatic hypotension.

COMPARATIVE EFFICACY OF YOHIMBINE AGAINST PYRIDOSTIGMINE FOR THE TREATMENT OF ORTHOSTATIC HYPOTENSION IN AUTONOMIC FAILURE

PubMed Central

Shibao, Cyndya; Okamoto, Luis E.; Gamboa, Alfredo; Yu, Chang; Diedrich, Andre'; Raj, Satish R.; Robertson, David; Biaggioni, Italo

2010-01-01

Orthostatic hypotension affects patients with autonomic failure producing considerable disability because of pre-syncopal symptoms. Severely affected patients may have residual sympathetic tone that can be engaged to increase blood pressure with the alpha-2 adrenergic antagonist yohimbine. This medication activates sympathetic outflow centrally and unrestrains norepinephrine release from noradrenergic neurons. Alternatively, the acetylcholinesterase inhibitor, pyridostigmine, can increase sympathetic tone by improving ganglionic cholinergic neurotransmission. Our purpose was to compare these complementary approaches and test the hypothesis that the combination would lead to synergistic increases in blood pressure. We compared the effects of pyridostigmine 60 mg and yohimbine 5.4 mg in a single-blind, randomized, placebo-controlled, crossover fashion. In a subset of patients we tested the combination of pyridostigmine and yohimbine. Our primary outcome was the change in standing diastolic blood pressure 60 minutes after drug administration from baseline. We studied a total of 31 patients with confirmed severe autonomic failure. Yohimbine significantly improved standing diastolic blood pressure as compared to placebo (11±3 mm Hg 95%CI: 6 to 16, P <0.001). On the contrary, Pyridostigmine did not increase the standing diastolic blood pressure (0.6±3 mm Hg 95%CI: −5 to 5, P =0.823). Only yohimbine showed a significant improvement in presyncopal symptoms. Sixteen patients received the combination of pyridostigmine and yohimbine, but no evidence of synergistic pressor effect was found. Engaging residual sympathetic tone with yohimbine is a more effective approach to improve orthostatic hypotension as compared to pyridostigmine in patients with severe orthostatic hypotension. PMID:20837887

Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease

PubMed Central

Sun, Zhanfang; Jia, Dandan; Shi, Yuting; Hou, Xuan; Yang, Xiaosu; Guo, Jifeng; Li, Nan; Wang, Junling; Sun, Qiying; Zhang, Hainan; Lei, Lifang; Shen, Lu; Yan, Xinxiang; Xia, Kun; Jiang, Hong; Tang, Beisha

2016-01-01

Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as “gold standard”. The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP ≥ 14 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP ≥ 18 mmHg or DBP ≥ 8 mmHg for severe OH. In PD group, drops in sitting SBP ≥ 10 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons. PMID:26867507

Midodrine as a Countermeasure to Orthostatic Hypotension Immediately After Space Shuttle Landing

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Ribeiro, L. Christine; Lee, Stuart M. C.

2010-01-01

Midodrine prevents post-space flight orthostatic intolerance when testing is conducted in a controlled laboratory setting within 2-4 hours after Space Shuttle landing. It is unknown if midodrine is as effective during re-entry and immediately following landing. METHODS: Cardiovascular responses to 10 minutes of 80 head-up tilt in five male astronauts were compared before and immediately after Space Shuttle missions. Preflight tests were conducted in the Johnson Space Center Cardiovascular Laboratory without midodrine. Post-flight testing was performed in the Crew Transport Vehicle on the Space Shuttle runway within 60 minutes of landing; midodrine was self-administered before re-entry. Survival analysis was performed (Gehan-Breslow test) to compare presyncope rates pre- to post-flight. Cardiovascular responses (last minute standing minus supine) to tilt before and after space flight were compared using paired t-tests. RESULTS: Midodrine did not prevent post-flight orthostatic hypotension in two of the five astronauts, but the rate of presyncope across the group did not increase (p=0.17) from pre- to post-flight. Also, although the change in heart rate from supine to the last minute of standing was not affected by space flight, systolic blood pressure decreased more (p=0.05) and diastolic blood pressure tended to decrease (p=0.08) after space flight. CONCLUSIONS: Accurate interpretation of the current results requires that similar data be collected in control subjects (without midodrine) on the CTV. However, drug interaction concerns with commonly used anti-emetics and potentiation of prolonged QTc intervals observed in long duration astronauts make the routine use of midodrine for immediate post-flight orthostatic hypotension unlikely. 2

Effects of orthostatic hypotension on cognition in Parkinson disease

PubMed Central

Centi, Justin; Freeman, Roy; Gibbons, Christopher H.; Neargarder, Sandy; Canova, Alexander O.

2017-01-01

Objective: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in Parkinson disease (PD) using a cross-sectional and within-group design. Methods: Individuals without dementia with idiopathic PD included 18 with OH (PDOH) and 19 without OH; 18 control participants were also included. Neuropsychological tests were conducted in supine and upright-tilted positions. Blood pressure was assessed in each posture. Results: The PD groups performed similarly while supine, demonstrating executive dysfunction in sustained attention and response inhibition, and reduced semantic fluency and verbal memory (encoding and retention). Upright posture exacerbated and broadened these deficits in the PDOH group to include phonemic fluency, psychomotor speed, and auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, with the PDOH group exhibiting a wider range of deficits in executive function and memory as well as significant changes in visuospatial function. Conclusions: Cognitive deficits in PD have been widely reported with assessments performed in the supine position, as seen in both our PD groups. Here we demonstrated that those with PDOH had transient, posture-mediated changes in excess of those found in PD without OH. These observed changes suggest an acute, reversible effect. Understanding the effects of OH due to autonomic failure on cognition is desirable, particularly as neuroimaging and clinical assessments collect data only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with OH has quality of life implications, and OH presents itself as a possible target for intervention in cognitive disturbance. PMID:27903817

Effect of strength training on orthostatic hypotension in older adults.

PubMed

Brilla, L R; Stephens, A B; Knutzen, K M; Caine, D

1998-01-01

This preliminary study attempted to identify the frequency of orthostatic hypotension (OH) in community dwelling older adults who volunteered to participate in an 8-week, heavy-resistance, strength-training program. It also assessed the effect of the strength-training program on OH. From a larger study (n = 53) on high-resistance strength training in older adults (mean age 71.4 +/- 6.6 years), a subset of subjects (n = 24), mean age 71.0 +/- 5.8 years, was evaluated who met at least one criterion for OH. All subjects were tested for resting blood pressures (BP) and heart rates (HR) in the supine, sitting, and standing positions. Also noted was their response to orthostatism in rising from a cot after 10 minutes and rising from a chair after 5 minutes. The subset was not different from the overall group in gender ratio, age, or effect of medication on BP. The treatment was an 8-week strength-training program at 80% of their one repetition maximum. Significant changes (P < 0.05) were shown in supine diastolic BP (+3.2 mm Hg), sitting systolic BP (-3.9), and standing HR (+4.9 beats per minute). In response to the orthostatic challenge, significant (P < 0.05) improvements were shown in systolic BP (+9.7 mm Hg), diastolic BP (+4.7), and HR (+3.2 beats per minute) for the rise from chair, and in diastolic BP (+6.7 mm Hg) rise from the cot. These data show that OH is not uncommon (45%) in community dwelling older adults. A strength training program in older adults has little effect on resting BP, but elicits a positive adaptation to an orthostatic challenge.

Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.

PubMed

White, William B; Hauser, Robert A; Rowse, Gerald J; Ziemann, Adam; Hewitt, L Arthur

2017-04-01

The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

NASA Technical Reports Server (NTRS)

Shi, Shang-Jin; Garcia, Kathleen M.; Meck, Janice V.

2003-01-01

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.

Evaluation of cerebral vasomotor reactivity in Parkinson's disease: is there any association with orthostatic hypotension?

PubMed

Zamani, Babak; Mehrabani, Mehrnoush; Fereshtehnejad, Seyed-Mohammad; Rohani, Mohammad

2011-06-01

Our aim was to look for a probable relationship between cerebral vasomotor reactivity (VMR) and orthostatic hypotension (OH) in Parkinson's disease (PD). This study was conducted on 44 patients with PD. Assessment of cerebral VMR was performed by means of transcranial Doppler (TCD) of middle cerebral artery (MCA) before and after a vasodilatory stimulus, carbon dioxide test. Moreover, orthostatic hypotension was evaluated. OH was presented in 12 (27.3%) Parkinson's patients. The average resting blood flow velocity (BFV) in the MCA was 30.20 (SD=9.58)cms(-1) which significantly increased to 46.25 (SD=16.23)cms(-1) after carbon dioxide test (P<0.001). Impaired VMR was observed in 15 (34.1%) of the subjects, while it was not associated with the presence of OH (P=0.770). Evaluation of VMR in patients affected by PD, could assist in early diagnosis of cerebral autonomic dysfunction and prevent its serious consequences prior and more valid to OH. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

The relationship between orthostatic hypotension and falling in older adults.

PubMed

Shaw, Brett H; Claydon, Victoria E

2014-02-01

Falls are devastating events and are the largest contributor towards injury-related hospitalization of older adults. Orthostatic hypotension (OH) represents an intrinsic risk factor for falls in older adults. OH refers to a significant decrease in blood pressure upon assuming an upright posture. Declines in blood pressure can reduce cerebral perfusion; this can impair consciousness, lead to dizziness, and increase the likelihood of a fall. Although theoretical mechanisms linking OH and falls exist, the magnitude of the association remains poorly characterized, possibly because of methodological differences between previous studies. The use of non-invasive beat-to-beat blood pressure monitoring has altered the way in which OH is now defined, and represents a substantial improvement for detecting OH that was previously unavailable in many studies. Additionally, there is a lack of consistency and standardization of orthostatic assessments and analysis techniques for interpreting blood pressure data. This review explores the previous literature examining the relationship between OH and falls. We highlight the impact of broadening the timing, degree, and overall duration of blood pressure measurements on the detection of OH. We discuss the types of orthostatic stress assessments currently used to evaluate OH and the various techniques capable of measuring these often transient blood pressure changes. Overall, we identify future solutions that may better clarify the relationship between OH and falling risk in order to gain a more precise understanding of potential mechanisms for falls in older adults.

Neurogenic orthostatic hypotension: roles of norepinephrine deficiency in its causes, its treatment, and future research directions.

PubMed

Loavenbruck, Adam; Sandroni, Paola

2015-11-01

Although a diversity of neurotransmitters and hormones participate in controlling blood pressure, norepinephrine released from postganglionic sympathetic nerve terminals is an important mediator of the rapid regulation of cardiovascular function required for homeostasis of cerebral perfusion. Hence, neurogenic orthostatic hypotension (NOH) often represents a deficiency of noradrenergic responsiveness to postural change. PubMed searches with 'orthostatic hypotension' and 'norepinephrine' as conjoint search terms and no restriction on language or date, so as to survey the pathophysiologic and clinical relevance of norepinephrine deficiency for current NOH interventions and for future directions in treatment and research. Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinson's disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). Nonpharmacologic countermeasures such as pre-emptive water intake may yield blood-pressure increases exceeding those achieved pharmacologically. For patients with symptomatic NOH unresponsive to such strategies, a variety of pharmacologic interventions have been administered off-label on the basis of drug mechanisms expected to increase blood pressure via blood-volume expansion or vasoconstriction. Two pressor agents have received FDA approval: the sympathomimetic midodrine and more recently the norepinephrine prodrug droxidopa. Pressor agents are important for treating symptomatic NOH in patients unresponsive to lifestyle changes alone. However, the dysautonomia underlying NOH often permits blood-pressure excursions toward both hypotension and hypertension. Future research should aim to shed light on the resulting management issues, and should also explore the possibility of pharmacotherapy selectively

[Orthostatic hypotension in the elderly].

PubMed

Ferrer-Gila, Teresa; Rízea, Cristian

2013-03-16

Orthostatic hypotension (OH) is defined as a decrease in systolic blood pressure of 20 mmHg, or a decrease in diastolic blood pressure of 10 mmHg within three minutes of standing. It results from an inadequate response to postural changes in blood pressure. Common symptoms include dizziness, light-headedness, blurred vision, weakness, fatigue, nausea, palpitations, sweating, head and neck ache, slow cognitive performance and transient loss of conscientiousness. OH is a common problem among elderly patients and its aetiology is diverse, including autonomic nervous system dysfunction, cardiac problems, medication side effects, ageing changes or transitory deregulation of blood volume. The instrumental diagnosis can be easily accomplished by the tilt-table test, with continuous monitoring of blood pressure and cardiac parameters. It is a non-invasive technique and needs minimal collaboration from the patient. In our experience, when reviewing 327 patients, aged over 40 years and examined because of clinical suspicion of OH, the prevalence thereof was 51% whereas if focused in subjects older than 70, OH was proven in 90% of the cases. The older the patients, the more frequently they presented general deterioration, neurological or cardiac problems as well as pharmacological side effects. Ruling out neurological or cardiac malfunction can drastically improve the prognosis with possible reversibility of symptoms. Some nonpharmacological and pharmacological approaches to improve management of OH and life quality are described for guidance.

Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension.

PubMed

Biaggioni, Italo; Arthur Hewitt, L; Rowse, Gerald J; Kaufmann, Horacio

2017-05-12

Droxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460). Efficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined. Droxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies. Droxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

PubMed

Mathias, C J; Senard, J M; Braune, S; Watson, L; Aragishi, A; Keeling, J E; Taylor, M D

2001-08-01

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension

PubMed Central

Palma, Jose-Alberto; Kaufmann, Horacio

2017-01-01

Background Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing which can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions particularly in the elderly (233 per 100,000 patients over 75 years of age in the US). OH can be due to volume depletion, blood loss, large varicose veins, medications, or due to defective activation of sympathetic nerves and reduced norepinephrine release upon standing (i.e., neurogenic OH). Methods and Findings Literature review. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and is commonly associated with supine hypertension. Several pharmacological and non-pharmacological therapeutic options are available. Conclusions Here we review the epidemiology, diagnosis, and management of neurogenic OH, and provide an algorithm for its treatment emphasizing the importance of removing aggravating factors, implementing non-pharmacologic measures, and selecting appropriate pharmacological treatments. PMID:28713844

Orthostatic hypotension and cognitive function: cross-sectional results from the ELSA-Brasil study.

PubMed

Suemoto, Claudia K; Baena, Cristina P; Mill, Jose G; Santos, Itamar S; Lotufo, Paulo A; Benseñor, Isabela

2018-03-20

The association between orthostatic hypotension (OH) and cognitive impairment is controversial, and most studies have investigated older white adults from Western Europe and the United States. Therefore, we investigated the association between OH and cognitive performance in a large and racially diverse sample of adults using cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). OH was defined when systolic blood pressures (SBP) decreased 20 mmHg and/or diastolic blood pressure (DBP) decreased 10 mmHg from supine to standing position. We investigated the association between OH and composite global cognition, memory, verbal fluency (VF), and Trail Making test z-scores, using multiple linear regression models. We also investigated the association of orthostatic hypertension and SBP/DBP changes with cognitive performance, as well as the interaction between OH and compensatory heart rate (HR) after postural change on cognitive performance. We evaluated 12,826 participants (mean age=51.5±9.0 years, 46% male, 53% white). Participants with OH (4% of the sample) had poorer z-scores for VF (β=-0.108, 95% CI=-0.189; -0.025, p=0.01) than participants without OH. Orthostatic hypertension was also associated with worse performance on the VF test (β=-0.080, 95% CI=-0.157; -0.003, p=0.04). SBP orthostatic change had a non-linear association with VF. The interaction terms between OH and compensatory increase in HR for the Trail Making Test z-score (p=0.09) was borderline significant, suggesting that participants who lack compensatory HR after postural change might have poorer performance. OH and orthostatic hypertension were associated with poorer performance on the VF test in participants from Brazil.

Orthostatic headache as the presenting symptom of cervical spine metastasis.

PubMed

Kim, Ji Hyun; Choi, Jeong-Yoon; Kim, Ho-Jung; Oh, Kyungmi

2008-01-01

Orthostatic headache is a key symptom of intracranial hypotension; however, not all orthostatic headaches are caused by cerebrospinal fluid leaks leading to intracranial hypotension. We report here the unusual case of a 68-year-old man presenting with orthostatic headache in which compression of the C3 spinal nerve root by metastatic tumor invasion may contribute to the development of his orthostatic headache.

Neurogenic orthostatic hypotension in Parkinson's disease: evaluation, management, and emerging role of droxidopa.

PubMed

Isaacson, Stuart H; Skettini, Julia

2014-01-01

Neurogenic orthostatic hypotension (nOH) is due to failure of the autonomic nervous system to regulate blood pressure in response to postural changes due to an inadequate release of norepinephrine, leading to orthostatic hypotension and supine hypertension. nOH is common in Parkinson's disease (PD). Prevalence varies throughout the course of PD, ranging from 40% to 60%, and resulting in symptomatic nOH in approximately half. Symptomatic nOH, including lightheadedness, can limit daily activities and lead to falls. Symptomatic nOH can also limit therapeutic options for treating PD motor symptoms. Clinical evaluation should routinely include symptom assessment and blood pressure measurement of supine, sitting, and 3-minute standing; 24-hour ambulatory blood pressure monitoring can also be helpful. Non-pharmacological management of symptomatic nOH involves education, physical maneuvers, and adequate hydration. Current pharmacological treatment of symptomatic nOH includes salt supplement, fludrocortisone, midodrine, pyridostigmine, and other empiric medications. Despite these options, treatment of symptomatic nOH remains suboptimal, often limited by severe increases in supine blood pressure. Droxidopa, an oral prodrug converted by decarboxylation to norepinephrine, is a promising therapeutic option for symptomatic nOH in PD, improving symptoms of nOH, daily activities, falls, and standing systolic blood pressure in several recent trials. These trials demonstrated short-term efficacy and tolerability, with comparable increases in standing and supine blood pressures. Longer-term studies are ongoing to confirm durability of treatment effect.

Orthostatic Hypotension and Elevated Resting Heart Rate Predict Low-Energy Fractures in the Population: The Malmö Preventive Project.

PubMed

Hamrefors, Viktor; Härstedt, Maria; Holmberg, Anna; Rogmark, Cecilia; Sutton, Richard; Melander, Olle; Fedorowski, Artur

2016-01-01

Autonomic disorders of the cardiovascular system, such as orthostatic hypotension and elevated resting heart rate, predict mortality and cardiovascular events in the population. Low-energy-fractures constitute a substantial clinical problem that may represent an additional risk related to such autonomic dysfunction. To test the association between orthostatic hypotension, resting heart rate and incidence of low-energy-fractures in the general population. Using multivariable-adjusted Cox regression models we investigated the association between orthostatic blood pressure response, resting heart rate and first incident low-energy-fracture in a population-based, middle-aged cohort of 33 000 individuals over 25 years follow-up. The median follow-up time from baseline to first incident fracture among the subjects that experienced a low energy fracture was 15.0 years. A 10 mmHg orthostatic decrease in systolic blood pressure at baseline was associated with 5% increased risk of low-energy-fractures (95% confidence interval 1.01-1.10) during follow-up, whereas the resting heart rate predicted low-energy-fractures with an effect size of 8% increased risk per 10 beats-per-minute (1.05-1.12), independently of the orthostatic response. Subjects with a resting heart rate exceeding 68 beats-per-minute had 18% (1.10-1.26) increased risk of low-energy-fractures during follow-up compared with subjects with a resting heart rate below 68 beats-per-minute. When combining the orthostatic response and resting heart rate, there was a 30% risk increase (1.08-1.57) of low-energy-fractures between the extremes, i.e. between subjects in the fourth compared with the first quartiles of both resting heart rate and systolic blood pressure-decrease. Orthostatic blood pressure decline and elevated resting heart rate independently predict low-energy fractures in a middle-aged population. These two measures of subclinical cardiovascular dysautonomia may herald increased risks many years in advance

Neurogenic orthostatic hypotension - management update and role of droxidopa.

PubMed

Vijayan, Joy; Sharma, Vijay K

2015-01-01

Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy.

L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience.

PubMed

Mathias, Christopher J

2008-03-01

Neurogenic orthostatic hypotension is a cardinal feature of generalised autonomic failure and commonly is the presenting sign in patients with primary autonomic failure. Orthostatic hypotension can result in considerable morbidity and even mortality and is a major management problem in disorders such as pure autonomic failure, multiple system atrophy and also in Parkinson's disease. Treatment is ideally two pronged, using non-pharmacological and pharmacological measures. Drug treatment ideally is aimed at restoring adequate amounts of the neurotransmitter noradrenaline. This often is not achievable because of damage to sympathetic nerve terminals, to autonomic ganglia or to central autonomic networks. An alternative is the use of sympathomimetics (that mimic the effects of noradrenaline, but are not identical to noradrenaline), in addition to other agents that target physiological mechanisms that contribute to blood pressure control.L-threo-dihydroxyphenyslerine (Droxidopa) is a pro-drug which has a structure similar to noradrenaline, but with a carboxyl group. It has no pressor effects in this form. It can be administered orally, unlike noradrenaline, and after absorption is converted by the enzyme dopa decarboxylase into noradrenaline thus increasing levels of the neurotransmitter which is identical to endogenous noradrenaline. Experience in Caucasians and in Europe is limited mainly to patients with dopamine beta hydroxylase deficiency. This review focuses on two studies performed in Europe, and provides information on its efficacy, tolerability and safety in patients with pure autonomic failure, multiple system atrophy and Parkinson's disease. It also addresses the issue of whether addition of dopa decarboxylase inhibitors, when combined with l-dopa in the treatment of the motor deficit in Parkinson's disease, impairs the pressor efficacy of Droxidopa.

Treatment of Post-SCI Hypotension

ClinicalTrials.gov

2018-02-15

Spinal Cord Injury; Autonomic Dysreflexia; Orthostatic Hypotension; Baroreceptor Integrity; Sympathetic Integrity; Vagal Integrity; Hypotension; Cerebral Blood Flow; Blood Pressure; Venous Occlusion Plethysmography

Neurogenic orthostatic hypotension in Parkinson’s disease: evaluation, management, and emerging role of droxidopa

PubMed Central

Isaacson, Stuart H; Skettini, Julia

2014-01-01

Neurogenic orthostatic hypotension (nOH) is due to failure of the autonomic nervous system to regulate blood pressure in response to postural changes due to an inadequate release of norepinephrine, leading to orthostatic hypotension and supine hypertension. nOH is common in Parkinson’s disease (PD). Prevalence varies throughout the course of PD, ranging from 40% to 60%, and resulting in symptomatic nOH in approximately half. Symptomatic nOH, including lightheadedness, can limit daily activities and lead to falls. Symptomatic nOH can also limit therapeutic options for treating PD motor symptoms. Clinical evaluation should routinely include symptom assessment and blood pressure measurement of supine, sitting, and 3-minute standing; 24-hour ambulatory blood pressure monitoring can also be helpful. Non-pharmacological management of symptomatic nOH involves education, physical maneuvers, and adequate hydration. Current pharmacological treatment of symptomatic nOH includes salt supplement, fludrocortisone, midodrine, pyridostigmine, and other empiric medications. Despite these options, treatment of symptomatic nOH remains suboptimal, often limited by severe increases in supine blood pressure. Droxidopa, an oral prodrug converted by decarboxylation to norepinephrine, is a promising therapeutic option for symptomatic nOH in PD, improving symptoms of nOH, daily activities, falls, and standing systolic blood pressure in several recent trials. These trials demonstrated short-term efficacy and tolerability, with comparable increases in standing and supine blood pressures. Longer-term studies are ongoing to confirm durability of treatment effect. PMID:24729712

Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial.

PubMed

Kaufmann, Horacio; Freeman, Roy; Biaggioni, Italo; Low, Phillip; Pedder, Simon; Hewitt, L Arthur; Mauney, Joe; Feirtag, Michael; Mathias, Christopher J

2014-07-22

To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days. © 2014 American Academy of Neurology.

Neurogenic orthostatic hypotension – management update and role of droxidopa

PubMed Central

Vijayan, Joy; Sharma, Vijay K

2015-01-01

Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy. PMID:26089676

Transcranial Doppler monitoring in Parkinson's disease: cerebrovascular compensation of orthostatic hypotension.

PubMed

Haubrich, Christina; Pies, Katrin; Dafotakis, Manuel; Block, Frank; Kloetzsch, Christof; Diehl, Rolf R

2010-10-01

Despite of precipitous blood pressure falls in Parkinson's Disease (PD) patients, they may not experience syncope or postural complaints. Can cerebral blood flow regulation explain why orthostatic hypotension (OH) has often no accompanying symptoms? In patients with PD and OH (18 asymptomatic; 8 symptomatic), arterial blood pressure (ABP) as well as Doppler-detected cerebral blood flow velocity (CBFV) in middle and posterior cerebral arteries (MCA and PCA) were monitored during head-up tilt and compared with 25 controls and eight non-PD-OH patients. Analysis included the transfer function between slow spontaneous pressure and flow-oscillations. ABP and CBFV were maintained at significantly higher levels in asymptomatic than symptomatic PD-OH (ABP: 85.7 ± 10.5 vs. 66.9 ± 12.5%; MCA-FV: 83.3 ± 9.3 vs. 66.1 ± 6.8%; PCA-FV: 84.4 ± 12.2 vs. 65.9 ± 9.3% of supine). When orthostatic complaints occurred, CBFV depended directly on ABP changes (MCA r(2) = 0.64; PCA r(2) = 0.62; both p < 0.05). Despite of a tilt-induced blood pressure instability in PD-OH, the transfer function parameters did not differ from normal [phase: MCA: 46.6 ± 20.5°; PCA 39.2 ± 28.8°, gain: MCA 2.0 ± 0.7; PCA 2.9 ± 1.6)]. Results showed a normal autoregulatory response to downward blood pressure shifts in PD. Moreover, orthostatic blood pressure instability is compensated equally sufficient in anterior and posterior parts of cerebral circulation. Whether in PD patients, OH becomes symptomatic rather seems to depend on blood pressure falling below the autoregulated range. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Efficacy of compression of different capacitance beds in the amelioration of orthostatic hypotension

NASA Technical Reports Server (NTRS)

Denq, J. C.; Opfer-Gehrking, T. L.; Giuliani, M.; Felten, J.; Convertino, V. A.; Low, P. A.

1997-01-01

Orthostatic hypotension (OH) is the most disabling and serious manifestation of adrenergic failure, occurring in the autonomic neuropathies, pure autonomic failure (PAF) and multiple system atrophy (MSA). No specific treatment is currently available for most etiologies of OH. A reduction in venous capacity, secondary to some physical counter maneuvers (e.g., squatting or leg crossing), or the use of compressive garments, can ameliorate OH. However, there is little information on the differential efficacy, or the mechanisms of improvement, engendered by compression of specific capacitance beds. We therefore evaluated the efficacy of compression of specific compartments (calves, thighs, low abdomen, calves and thighs, and all compartments combined), using a modified antigravity suit, on the end-points of orthostatic blood pressure, and symptoms of orthostatic intolerance. Fourteen patients (PAF, n = 9; MSA, n = 3; diabetic autonomic neuropathy, n = 2; five males and nine females) with clinical OH were studied. The mean age was 62 years (range 31-78). The mean +/- SEM orthostatic systolic blood pressure when all compartments were compressed was 115.9 +/- 7.4 mmHg, significantly improved (p < 0.001) over the head-up tilt value without compression of 89.6 +/- 7.0 mmHg. The abdomen was the only single compartment whose compression significantly reduced OH (p < 0.005). There was a significant increase of peripheral resistance index (PRI) with compression of abdomen (p < 0.001) or all compartments (p < 0.001); end-diastolic index and cardiac index did not change. We conclude that denervation increases vascular capacity, and that venous compression improves OH by reducing this capacity and increasing PRI. Compression of all compartments is the most efficacious, followed by abdominal compression, whereas leg compression alone was less effective, presumably reflecting the large capacity of the abdomen relative to the legs.

Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson's disease (nOH306B).

PubMed

Hauser, Robert A; Isaacson, Stuart; Lisk, Jerome P; Hewitt, L Arthur; Rowse, Gerry

2015-04-15

Neurogenic orthostatic hypotension (nOH) results from failure of norepinephrine responses to postural change to maintain standing systolic blood pressure (s-SBP). Droxidopa is an oral prodrug of norepinephrine. Study nOH306 enrolled patients with Parkinson's disease (PD) and symptomatic nOH. Subjects underwent up to 2 weeks of double-blind titration of droxidopa or placebo, followed by 8 weeks of double-blind maintenance treatment (100-600 mg thrice-daily). For the initial 51 subjects (study nOH306A, previously reported), the primary efficacy measure, Orthostatic Hypotension Questionnaire (OHQ) composite score, did not demonstrate significant change versus placebo at maintenance week 8. For the subsequent 171 subjects (study nOH306B, reported here), the primary efficacy measure was change versus placebo on item 1 ("dizziness, lightheadedness, feeling faint, or feeling like you might black out") of the Orthostatic Hypotension Symptom Assessment (OHSA) subsection of the OHQ at maintenance week 1. At week 1, mean (standard deviation) improvement on OHSA item 1 was 2.3 (2.95) for droxidopa versus 1.3 (3.16) for placebo (P = 0.018). In addition, mean increase in s-SBP at week 1 was 6.4 (18.85) for droxidopa versus 0.7 (20.18) mmHg for placebo (nominal P value: 0.032). Differences in change in OHSA item 1 scores from baseline to maintenance weeks 2, 4, and 8 were not statistically significant. Adverse-event (AE) incidence was similar across groups, but 12.4% of droxidopa and 6.1% of placebo subjects withdrew because of AEs. The most common AEs on droxidopa (vs. placebo) were headache (13.5% vs. 7.3%) and dizziness (10.1% vs. 4.9%). Study nOH306B demonstrated subjective (OHSA item 1) and objective (s-SBP) evidence of short-term droxidopa efficacy (vs. placebo) for symptomatic nOH in PD. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

A randomized trial of Korodin Herz-Kreislauf-Tropfen as add-on treatment in older patients with orthostatic hypotension.

PubMed

Kroll, M; Ring, C; Gaus, W; Hempel, B

2005-06-01

In a randomized, double-blind, placebo-controlled, parallel group, phase III clinical trial efficacy and safety of Korodin, a combination of natural D-camphor and an extract from fresh crataegus berries, was investigated in patients 50 years and older with orthostatic hypotension. At visit 1 eligibility of patients was checked and a placebo medication was given to all patients. At visit 2 orthostatic hypotension had to be reconfirmed, then the patient was randomized either to Korodin or placebo, study medication (25 drops) was applied once and then outcome was measured. After 7 days of home treatment with daily 3 x 25 drops outcome was measured at visit 3. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were documented 10, 5, 2 and 0 min before as well as 1, 3, 5, 8, and 10 min after getting in the upright position at visit 1, at visit 2 before and after application of study medication and at visit 3. Primary outcome was the change of mean arterial blood pressure (MAP) from just before standing up to the nadir within the first 3 min after standing up. Secondary outcome variables were SBP, DBP, HR, quality of life (SF-12) and seven typical signs and symptoms of orthostatic hypotension. The study was performed in a rehabilitation clinic and in two doctor's practices in Germany from November 2002 to May 2003. During this time, 57 patients were admitted to the study, 39 patients were eligible and randomized, 38 patients were treated according to protocol and evaluated, 21 patients with Korodin and 17 patients with placebo. After a single application the median decrease of MAP was 11.4 mmHg for Korodin and 14.0 mmHg for placebo. Compared to baseline, the median MAP improved 4.3 mmHg for Korodin and 0.3 mmHg for placebo. After 1 week of treatment the decrease of median MAP after standing up was 9.3 mmHg for Korodin and 13.3 mmHg for placebo. Compared to baseline, the improvement was 5.9 mmHg for Korodin and 1.6 mmHg for placebo. Efficacy

Droxidopa for Symptomatic Neurogenic Hypotension.

PubMed

Ferguson-Myrthil, Nadia

Droxidopa is a first-in-class, orally available, synthetic amino acid precursor of norepinephrine that received accelerated Food and Drug Administration approval in February 2014 after Orphan Drug status for a debilitating condition known as symptomatic neurogenic orthostatic hypotension. Neurogenic disorders often lead to postural hypotension as a result of poor norepinephrine release from its storage sites. Clinical data suggest increases in standing systolic blood pressure and improvements in many other markers for subjective relief in patients with symptomatic neurogenic hypotension who received droxidopa therapy over 1-2 weeks. Studies evaluating the sustained effects of droxidopa are ongoing. With minimal drug interactions (even with carbidopa use) or adverse effects, droxidopa therapy can be used safely in patients with a variety of neurologic conditions; however, more data are needed to determine its appropriate pharmacotherapeutic role. In all, droxidopa is a safe and effective medication for the treatment of orthostatic dizziness/lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension secondary to primary autonomic failure (Parkinson's disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.

The association between orthostatic hypotension, falling and successful rehabilitation in a nursing home population.

PubMed

Hartog, L C; Cizmar-Sweelssen, M; Knipscheer, A; Groenier, K H; Kleefstra, N; Bilo, H J G; van Hateren, K J J

2015-01-01

Our objectives were to identify the prevalence of orthostatic hypotension (OH) in frail, elderly nursing home residents, and assess its possible association with falling and chances of successful rehabilitation. A prospective observational cohort study. A total of 290 patients participated in this study, of which 128 were admitted to the rehabilitation department. OH was defined as a drop in systolic blood pressure of >20mmHg and diastolic blood pressure of >10mmHg after postural change within 3min. The analyses regarding falling and successful rehabilitation were only performed in the rehabilitation group. Multivariate binary logistic regression analyses were used to describe risk factors related with falling. Cox proportional hazard modeling was used to investigate the relation between OH and the time to successful rehabilitation. The prevalence of OH in the studied nursing home population was 36.6% (95% CI (confidence interval): 31.1-42.1%). The prevalence varied from 28.6% (95% CI: 16.8-40.4%) in somatic patients, 36.7% (95% CI: 28.4-45.1%) in rehabilitation patients, to 40.6% (95% CI: 31.3-50.0%) in psychogeriatric patients. The association between orthostatic hypotension and previous falling was not significant; Odds ratio 0.66 (95% CI: 0.30-1.48). The Hazard ratio of the relationship between OH and successful rehabilitation was 2.88 (95% CI:1.77-4.69). OH is highly prevalent in nursing home residents. Surprisingly, patients with OH were found to have a higher chance of successful rehabilitation compared to patients without OH. If confirmed in other studies, these results may change our view of the implications of OH. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing vasculature?

PubMed

Kwok, C S; Ong, A C L; Potter, J F; Metcalf, A K; Myint, P K

2014-06-01

We sought to identify the determinants of orthostatic hypotension (OH) among patients referred to the transient ischaemic attack (TIA) clinic. We conducted a retrospective analysis of prospectively collected data on patients who attended the TIA clinic in a UK hospital between January 2006 and September 2009. Each patient had their supine and standing or sitting blood pressure measured. Logistic regression was used to estimate the univariate and multivariate odds of OH for the subgroups of patients based on their diagnosis. A 10% significance level for the univariate analysis was used to identify variables in the multivariate model. A total of 3222 patients were studied of whom 1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of either systolic or diastolic OH in the TIA, stroke and patients with other diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292), respectively. Multivariate analyses showed age, prior history of TIA, and diabetes were independently significantly associated with systolic OH alone or diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56 (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the diagnosis of stroke, peripheral vascular disease (PVD) was significantly associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a significantly lower odds of OH (0.61, 0.42-0.88). In patients with other diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH. Orthostatic hypotension is prevalent among patients presenting to TIA clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be a significant associate of OH in this patient population. © 2014 John Wiley & Sons Ltd.

Endogenous circulating sympatholytic factor in orthostatic intolerance

NASA Technical Reports Server (NTRS)

Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.

2000-01-01

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Orthostatic changes in blood pressure and mortality in a nursing home population.

PubMed

Hartog, Laura C; Hendriks, Steven H; Cimzar-Sweelssen, Mateja; Knipscheer, Astrid; Groenier, Klaas H; Kleefstra, Nanne; Bilo, Henk J G; van Hateren, Kornelis J J

2016-06-01

Hypertension, orthostatic hypotension and orthostatic hypertension (OHT) are highly prevalent in old age. The associations in the very elderly and frail patients between blood pressure, and especially orthostatic changes in blood pressure, and mortality are unclear. We aimed to investigate the relationships between orthostatic changes in blood pressure, blood pressure and mortality in nursing home residents. A prospective observational cohort study. Cox proportional hazard modelling was used to investigate the relation between orthostatic hypotension, OHT, the various blood pressure variables and mortality with adjustment for confounders. In the case of significant associations in the models, risk prediction capabilities were assessed with Harrell's C statistics and the proportion of explained variance (R). Two hundred and ninety patients with a mean age of 80.8 (SD 9.9) years participated in this study. The overall mortality risk increased by 17% [95% confidence interval (CI): 2-34%] for every 10-mmHg increase in DBP. Adding DBP did not change Harrell's C values and increased R with 0.03 or less. Only in patients at the psychogeriatric department, orthostatic hypotension was associated with an increased all-cause mortality risk [hazard ratio (HR) 1.71 (95% CI: 1.08-2.71%)]. The HR of OHT in this patient group was 0.61 (95% CI: 0.32-1.19%). DBP was related to all-cause mortality in a nursing home population. Orthostatic hypotension was related to all-cause mortality in the most frail group of nursing home patients. The predictive capabilities of both DBP and orthostatic hypotension are rather small with respect to mortality. A beneficial effect of OHT could not be excluded on the basis of the width of the CI.

Pyridostigmine in the treatment of orthostatic intolerance.

PubMed

Gales, Barry J; Gales, Mark A

2007-02-01

To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. MEDLINE and International Pharmaceutical Abstracts were searched (1966-December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long

Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A).

PubMed

Hauser, Robert A; Hewitt, L Arthur; Isaacson, Stuart

2014-01-01

Neurogenic orthostatic hypotension (nOH) is common in Parkinson's disease (PD), and represents a failure to generate norepinephrine responses appropriate for postural change. Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an oral norepinephrine prodrug. Interim analyses of the initial patients enrolled in a multicenter, randomized, double-blind, placebo-controlled phase 3 trial of droxidopa for nOH in PD (ClinicalTrials.gov Identifier: NCT01176240). PD patients with documented nOH underwent ≤ 2 weeks of double-blind droxidopa or placebo dosage optimization followed by 8 weeks of maintenance treatment (100-600 mg t.i.d.). The primary efficacy measure was change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to Week 8. Key secondary variables included dizziness/lightheadedness score (OHQ item 1) and patient-reported falls. Among 24 droxidopa and 27 placebo recipients, mean OHQ composite-score change at Week 8 was -2.2 versus -2.1 (p = 0.98); in response to this pre-planned futility analysis, the study was temporarily stopped and all data from these patients were considered exploratory. At Week 1, mean dizziness/lightheadedness score change favored droxidopa by 1.5 units (p = 0.24), with subsequent numerical differences favoring droxidopa throughout the observation period, and at Week 1, mean standing systolic blood-pressure change favored droxidopa by 12.5 mmHg (p = 0.04). Compared with placebo, the droxidopa group exhibited an approximately 50% lower rate of reported falls (p = 0.16) and fall-related injuries (post-hoc analysis). This exploratory analysis of a small dataset failed to show benefit of droxidopa, as compared with placebo by the primary endpoint. Nonetheless, there were signals of potential benefit for nOH, including improvement in dizziness/lightheadedness and reduction in falls, meriting evaluation in further trials.

Increased sympathetic activation in idiopathic orthostatic intolerance: role of systemic adrenoreceptor sensitivity

NASA Technical Reports Server (NTRS)

Jordan, Jens; Shannon, John R.; Diedrich, Andre; Black, Bonnie K.; Robertson, David

2002-01-01

Idiopathic orthostatic intolerance (OI) is characterized by adrenergic symptoms with standing. Changes in central sympathetic tone or in adrenoreceptor sensitivity could contribute to this syndrome. In OI patients and control subjects, we determined heart rate (HR) and systolic blood pressure (SBP) changes after incremental bolus doses of isoproterenol and phenylephrine before and during ganglionic blockade with trimethaphan. SBP decreased by 17+/-1.6 mm Hg in patients and 3.9+/-3.8 mm Hg in control subjects (P<0.01) with trimethaphan. Patients with a larger decrease (28+/-3.8 mm Hg, n=7) in SBP with trimethaphan had greater supine SBP and supine and upright plasma norepinephrine levels than did patients with a lesser decrease (3.0+/-3.0 mm Hg, n=7) in SBP. Supine and orthostatic HRs were similar for the groups. The majority of patients had a normal HR response to isoproterenol before and during ganglionic blockade. Phenylephrine increased SBP similarly in patients and control subjects before and during blockade. Sympathetic support is increased in a subgroup of OI patients. Hyperadrenergic and nonhyperadrenergic subgroups have similar degrees of orthostatic tachycardia. Our findings suggest that the hyperadrenergic features of OI cannot be completely explained by systemic hypersensitivity of postsynaptic alpha(1)- and beta-adrenoreceptors but rather originates in enhanced sympathetic activation.

Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Hewitt, L Arthur; Rowse, Gerald J; White, William B

2016-10-01

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour "off-drug" data were collected. "On-drug" assessment was conducted after 4-5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 ± 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP ≥10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

François, Clément; Rowse, Gerald J; Hewitt, L Arthur; Vo, Pamela; Hauser, Robert A

2016-08-18

Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH). Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo. The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ≥2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively. Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

Orthostatic Hypotension and Mortality in Elderly Frail Patients

PubMed Central

Freud, Tamar; Punchik, Boris; Yan, Press

2015-01-01

Abstract Orthostatic hypotension (OH) is a common problem in the elderly age group, and some studies have reported an association between OH and increased mortality. We evaluated possible associations between OH and mortality in a retrospective study of frail elderly patients who came for a comprehensive geriatric assessment. The study included all patients ≥65 years who were assessed in the outpatient Comprehensive Geriatric Assessment Unit. Data were collected from the computerized medical record, including blood pressure, sociodemographic data, lifestyle, falls, pulse rate, body mass index, functional and cognitive status, and comorbidity. Data on mortlaity were also collected. The study population consisted of 571 patients who underwent assessment over a 9-year study period. The mean age was 83.7 ± 6.1, 35.9% were males, and 183 (32.1%) were diagnosed with OH. Systolic OH (OHS) was more common than diastolic OH (25.2% vs 15.6%). In univariate analyses, OHS was associated with increased overall mortality. Over the follow-up period, 30.2% of the OHS patients died compared with 22.3% (P = 0.037), but in the Cox models there was no statistically significant associations between OHS and overall mortality. In contrast, age, burden of comorbidity, a low high-density lipoprotein level, and low creatinine clearance were independent predictors of increased overall mortality. In a population of frail elderly patients with a high burden of comorbidity, OH was not an independent risk factor for overall mortality. PMID:26091470

Orthostatic Changes in Blood Pressure and Cognitive Status in the Elderly: The Progetto Veneto Anziani Study.

PubMed

Curreri, Chiara; Giantin, Valter; Veronese, Nicola; Trevisan, Caterina; Sartori, Leonardo; Musacchio, Estella; Zambon, Sabina; Maggi, Stefania; Perissinotto, Egle; Corti, Maria Chiara; Crepaldi, Gaetano; Manzato, Enzo; Sergi, Giuseppe

2016-08-01

We studied a cohort of 1408 older subjects to explore whether postural changes in blood pressure (BP; defined as orthostatic hypo- or hypertension) can predict the onset of cognitive deterioration. Orthostatic hypotension was defined as a drop of 20 mm Hg in systolic or 10 mm Hg in diastolic BP and orthostatic hypertension as a rise of 20 mm Hg in systolic BP. Orthostatic BP values were grouped into quintiles for secondary analyses. Two cognitive assessments were considered: (1) cognitive impairment, that is, Mini-Mental State Examination scores ≤24/30, and (2) cognitive decline (CD), that is, a 3-point decrease in Mini-Mental State Examination score from the baseline to the follow-up. At the baseline, the prevalence of orthostatic hypotension and hypertension was 18.3% and 10.9%, respectively. At the follow-up (4.4±1.2 years), 286 participants were found cognitively impaired and 138 had a CD. Using logistic regression analysis adjusted for potential baseline confounders, participants with orthostatic hypertension were at significantly higher risk of CD (odds ratio =1.50; 95% confidence intervals =1.26-1.78). Neither orthostatic hypotension nor orthostatic hypertension raised the risk of developing a cognitive impairment. Using quintiles of orthostatic BP values, we found that both decreases and increases in systolic and diastolic BP raised the risk of CD, but not of cognitive impairment. In conclusion, we found that orthostatic hypertension predicts the onset of CD, but not of cognitive impairment in the elderly, whereas orthostatic hypotension predicts neither of these conditions. Further studies are needed to confirm our findings. © 2016 American Heart Association, Inc.

Gender-Related Differences in Cardiovascular Responses to Orthostatic Stress

NASA Technical Reports Server (NTRS)

Fritsch-Yelle, Janice M.; DAunno, Dominick S.; Waters, Wendy W.; Freeman-Perez, Sondra

1999-01-01

There is evidence that men and women have different cardiovascular responses to standing, and that women are more susceptible to orthostatic hypotension than men. The present study seeks to determine if decreased orthostatic tolerance in women is caused by diminished vasoconstrictive responses.

EFFICACY OF SERVO-CONTROLLED SPLANCHNIC VENOUS COMPRESSION IN THE TREATMENT OF ORTHOSTATIC HYPOTENSION. A RANDOMIZED COMPARISON WITH MIDODRINE

PubMed Central

Okamoto, Luis E.; Diedrich, André; Baudenbacher, Franz J.; Harder, René; Whitfield, Jonathan S.; Iqbal, Fahad; Gamboa, Alfredo; Shibao, Cyndya A.; Black, Bonnie K.; Raj, Satish R.; Robertson, David; Biaggioni, Italo

2016-01-01

Splanchnic venous pooling is a major hemodynamic determinant of orthostatic hypotension (OH), but is not specifically targeted by pressor agents, the mainstay of treatment. We developed an automated inflatable abdominal binder that provides sustained servo-controlled venous compression (40 mmHg) and can be activated only on standing. We tested the efficacy of this device against placebo and compared it to midodrine in nineteen autonomic failure patients randomized to receive either placebo, midodrine (2.5–10 mg) or placebo combined with binder on separate days in a single-blind, crossover study. Systolic blood pressure (SBP) was measured seated and standing before and 1-hour post-medication; the binder was inflated immediately before standing. Only midodrine increased seated SBP (31±5 vs. 9±4 placebo and 7±5 binder, P=0.003); whereas orthostatic tolerance (defined as area under the curve of upright SBP [AUCSBP]) improved similarly with binder and midodrine (AUCSBP, 195±35 and 197±41 vs. 19±38 mmHg*min for placebo, P=0.003). Orthostatic symptom burden decreased with the binder (from 21.9±3.6 to 16.3±3.1, P=0.032) and midodrine (from 25.6±3.4 to 14.2±3.3, P<0.001), but not with placebo (from 19.6±3.5 to 20.1±3.3, P=0.756). We also compared the combination of midodrine and binder, with midodrine alone. The combination produced a greater increase in orthostatic tolerance (AUCSBP, 326±65 vs. 140±53 mmHg*min for midodrine alone, P=0.028, n=21), and decreased orthostatic symptoms (from 21.8±3.2 to 12.9±2.9, P<0.001). In conclusion, servo-controlled abdominal venous compression with an automated inflatable binder is as effective as midodrine, the standard of care, in the management of OH. Combining both therapies produces greater improvement in orthostatic tolerance. PMID:27271310

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

PubMed Central

Natelson, Benjamin H; Intriligator, Roxann; Cherniack, Neil S; Chandler, Helena K; Stewart, Julian M

2007-01-01

Context Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance. Objective To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls. Design Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs. Setting Referral practice and research center. Participants 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test. Main outcome measures Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof. Results CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests. Conclusion A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition. PMID:17263876

Low Blood Pressure (Hypotension)

MedlinePlus

... Low blood pressure on standing up (orthostatic, or postural, hypotension). This is a sudden drop in blood ... progressive damage to the autonomic nervous system, which controls involuntary functions such as blood pressure, heart rate, ...

Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).

PubMed

Isaacson, Stuart; Shill, Holly A; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J

2016-10-19

Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms.

Pyridostigmine treatment trial in neurogenic orthostatic hypotension.

PubMed

Singer, Wolfgang; Sandroni, Paola; Opfer-Gehrking, Tonette L; Suarez, Guillermo A; Klein, Caroline M; Hines, Stacy; O'Brien, Peter C; Slezak, Jeffrey; Low, Phillip A

2006-04-01

Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension. To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo. We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given. No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms. Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.

Autoregulation of cerebral blood flow in orthostatic hypotension

NASA Technical Reports Server (NTRS)

Novak, V.; Novak, P.; Spies, J. M.; Low, P. A.

1998-01-01

BACKGROUND AND PURPOSE: We sought to evaluate cerebral autoregulation in patients with orthostatic hypotension (OH). METHODS: We studied 21 patients (aged 52 to 78 years) with neurogenic OH during 80 degrees head-up tilt. Blood flow velocities (BFV) from the middle cerebral artery were continuously monitored with transcranial Doppler sonography, as were heart rate, blood pressure (BP), cardiac output, stroke volume, CO2, total peripheral resistance, and cerebrovascular resistance. RESULTS: All OH patients had lower BP (P<.0001), BFV_diastolic (P<.05), CVR (P<.007), and TPR (P<.02) during head-up tilt than control subjects. In control subjects, no correlations between BFV and BP were found during head-up tilt, suggesting normal autoregulation. OH patients could be separated into those with normal or expanded autoregulation (OH_NA; n=16) and those with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either no correlation between BFV and BP (n=8) or had a positive BFV/BP correlation (R2>.75) but with a flat slope. An expansion of the "autoregulated" range was seen in some patients. The OH_AF group was characterized by a profound fall in BFV in response to a small reduction in BP (mean deltaBP <40 mm Hg; R2>.75). CONCLUSIONS: The most common patterns of cerebral response to OH are autoregulatory failure with a flat flow-pressure relationship or intact autoregulation with an expanded autoregulated range. The least common pattern is autoregulatory failure with a steep flow-pressure relationship. Patients with patterns 1 and 2 have an enhanced capacity to cope with OH, while those with pattern 3 have reduced capacity.

L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy.

PubMed

Gibbons, Christopher H; Vernino, Steven A; Kaufmann, Horacio; Freeman, Roy

2005-10-11

The authors report a 46-year-old woman with antibodies to the nicotinic acetylcholine receptor (NiAchR) of the autonomic ganglia. She presented with severe orthostatic intolerance refractory to treatment with midodrine, fludrocortisone, erythropoietin, vasopressin, salt, and fluid loading. Addition of L-threo-3,4-dihidroxyphenylserine (L-DOPS) substantially improved blood pressure and orthostatic tolerance. L-DOPS may benefit patients with severe orthostatic intolerance and be particularly effective in patients with ganglionic NiAchR antibodies.

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

NASA Technical Reports Server (NTRS)

Meck, Janice V.; Waters, Wendy W.; Ziegler, Michael G.; deBlock, Heidi F.; Mills, Paul J.; Robertson, David; Huang, Paul L.

2004-01-01

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.

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

PubMed

Meck, Janice V; Waters, Wendy W; Ziegler, Michael G; deBlock, Heidi F; Mills, Paul J; Robertson, David; Huang, Paul L

2004-04-01

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.

Intracranial hypotension and hypertension in children and adolescents.

PubMed

Ozge, Aynur; Bolay, Hayrunnisa

2014-07-01

The specific aim of this review is to report the features of intracranial pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH)] in children and adolescents, with emphasis on the presentation, diagnosis, and treatment modalities. Headache associated with intracranial pressure changes are relatively rare and less known in children and adolescents. SIH is a specific syndrome involving reduced intracranial pressure with orthostatic headache, frequently encountered connective tissue disorders, and a good prognosis with medical management, initial epidural blood patching, and sometimes further interventions may be required. IIH is an uncommon condition in children and different from the disease in adults, not only with respect to clinical features (likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus) but also different in outcome. Consequently, specific ICP changes of pediatric ages required specific attention both of exact diagnosis and entire management.

Vestibulosympathetic reflex during orthostatic challenge in aging humans

NASA Technical Reports Server (NTRS)

Monahan, Kevin D.; Ray, Chester A.

2002-01-01

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.

Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial.

PubMed

Schreglmann, S R; Büchele, F; Sommerauer, M; Epprecht, L; Kägi, G; Hägele-Link, S; Götze, O; Zimmerli, L; Waldvogel, D; Baumann, C R

2017-04-01

Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with

Orthostatic Hypotension: A Practical Approach to Investigation and Management.

PubMed

Arnold, Amy C; Raj, Satish R

2017-12-01

The maintenance of blood pressure upon the assumption of upright posture depends on rapid cardiovascular adaptations driven primarily by the autonomic nervous system. Failure of these compensatory mechanisms can result in orthostatic hypotension (OH), defined as sustained reduction in systolic blood pressure > 20 mm Hg or diastolic blood pressure > 10 mm Hg within 3 minutes of standing or > 60° head-up tilt. OH is a common finding, particularly in elderly populations, associated with cardiovascular and cerebrovascular morbidity and mortality. Therefore, it is important to identify OH in the clinical setting. The detection of OH requires blood pressure measurements in the supine and standing positions. A more practical approach in clinics might be measurement of seated and standing blood pressure, but this can produce smaller depressor responses because of reduced gravitational stress. Heart rate responses to standing should be concomitantly measured to assess integrity of baroreflex function. Patients with OH can present with symptoms of cerebral hypoperfusion on standing predisposing to syncope and falls; however, many patients are asymptomatic. When the diagnosis of OH is established, it is important to document potentially deleterious medications and comorbidities and to assess for neurogenic autonomic impairment to establish underlying causes. Treatment should be initiated in a structured and stepwise approach starting with nonpharmacological interventions (eg, lifestyle modifications and physical countermanoeuvres), and adding pharmacological interventions as needed in patients with severe OH (eg, midodrine, droxidopa, fludrocortisone). The treatment goal in OH should be to improve symptoms and functional status, and not to target arbitrary blood pressure values. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Sympathetic vasoconstriction and orthostatic intolerance after simulated microgravity.

PubMed

Kamiya, A; Michikami, D; Fu, Q; Iwase, S; Mano, T

1999-07-01

Upon a return to the earth from spaceflight, astronauts often become presyncope during standing. This orthostatic intolerance is provoked by the exposure to the stimulation model of microgravitational environment in humans, 6 degrees head-down bed rest (HDBR). The mechanism for the orthostatic hypotension after microgravity remains unclear. It has been reported that a microgravity-induced loss of circulatory blood volume, a withdrawal of vagal tone, or a reduction of carotid-cardiac baroreflex function may relate to this phenomenon. A recent article has reported that astronauts who showed presyncopal events after spaceflight had subnormal increases in plasma norepinephrine under the standing tests, suggesting that a hypoadrenergic responsiveness to orthostatic stress may partly contribute to postflight orthostatic hypotension. However, it is unclear how and whether or not the sympathetic outflow to peripheral vessels and the release of norepinephrine from sympathetic nerve terminals were altered after microgravity. The vasomotor sympathetic outflow to the skeletal muscle can be directly recorded as muscle sympathetic nerve activity (MSNA) using a microneurographic technique. In addition, the rate of an increase in plasma norepinephrine per that in MSNA in response to applied orthostatic stress can partly indicate the norepinephrine release to sympathetic stimuli as a trial assessment. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, and examined the differences in the MSNA response and the indicated norepinephrine release during HUT tests between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

PubMed

Iida, Nobutoshi; Koshikawa, Syozo; Akizawa, Tadao; Tsubakihara, Yoshiharu; Marumo, Fumiaki; Akiba, Takashi; Kawaguchi, Yoshindo; Imada, Akio; Yamazaki, Chikao; Suzuki, Masashi

2002-01-01

Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration. Copyright 2002 S. Karger AG, Basel

Orthostatic Hypotension in Middle-Age and Risk of Falls.

PubMed

Juraschek, Stephen P; Daya, Natalie; Appel, Lawrence J; Miller, Edgar R; Windham, Beverly Gwen; Pompeii, Lisa; Griswold, Michael E; Kucharska-Newton, Anna; Selvin, Elizabeth

2017-02-01

One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent. We conducted a prospective study of the association between baseline OH (1987-1989) and risk of falls in the Atherosclerosis Risk in Communities (ARIC) Study. Falls were ascertained during follow-up via ICD-9 hospital discharge codes or Centers for Medicare & Medicaid Services claims data. OH was defined as a drop in systolic blood pressure (SBP) ≥20mm Hg or diastolic blood pressure (DBP) ≥10mm Hg within 2 minutes of moving from the supine to standing position. Changes in SBP or DBP during OH assessments were also examined as continuous variables. During a median follow-up of 23 years, there were 2,384 falls among 12,661 participants (mean age 54 years, 55% women, 26% black). OH was associated with risk of falls even after adjustment for demographic characteristics and other risk factors (hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.10, 1.54; P = 0.002). Postural change in DBP was more significantly associated with risk of falls (HR 1.09 per -5mm Hg change in DBP; 95% CI: 1.05, 1.13; P < 0.001) than postural change in SBP (HR 1.03 per -5mm Hg change in SBP; 95% CI: 1.01, 1.05; P = 0.002). In a community-based, middle-aged population, OH, and in particular, postural change in DBP, were independent risk factors for falls over 2 decades of follow-up. Future studies are needed to examine OH thresholds associated with increased risk of falls. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Orthostatic Hypotension in Middle-Age and Risk of Falls

PubMed Central

Juraschek, Stephen P.; Daya, Natalie; Appel, Lawrence J.; Miller, Edgar R.; Windham, Beverly Gwen; Pompeii, Lisa; Griswold, Michael E.; Kucharska-Newton, Anna

2017-01-01

BACKGROUND One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent. METHODS We conducted a prospective study of the association between baseline OH (1987–1989) and risk of falls in the Atherosclerosis Risk in Communities (ARIC) Study. Falls were ascertained during follow-up via ICD-9 hospital discharge codes or Centers for Medicare & Medicaid Services claims data. OH was defined as a drop in systolic blood pressure (SBP) ≥20mm Hg or diastolic blood pressure (DBP) ≥10mm Hg within 2 minutes of moving from the supine to standing position. Changes in SBP or DBP during OH assessments were also examined as continuous variables. RESULTS During a median follow-up of 23 years, there were 2,384 falls among 12,661 participants (mean age 54 years, 55% women, 26% black). OH was associated with risk of falls even after adjustment for demographic characteristics and other risk factors (hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.10, 1.54; P = 0.002). Postural change in DBP was more significantly associated with risk of falls (HR 1.09 per −5mm Hg change in DBP; 95% CI: 1.05, 1.13; P < 0.001) than postural change in SBP (HR 1.03 per −5mm Hg change in SBP; 95% CI: 1.01, 1.05; P = 0.002). CONCLUSIONS In a community-based, middle-aged population, OH, and in particular, postural change in DBP, were independent risk factors for falls over 2 decades of follow-up. Future studies are needed to examine OH thresholds associated with increased risk of falls. PMID:27638848

Delaying Orthostatic Syncope With Mental Challenge

NASA Astrophysics Data System (ADS)

Goswami, Nandu; Roessler, Andreas; Hinghofer-Szalkay, Helmut; Montani, Jean-Pierre; Steptoe, Andrew

2012-07-01

At orthostatic vasovagal syncope there appears to be a sudden withdrawl of sympathetic activity. As mental challenge activates the sympathetic system, we hypothesized that doing mental arithmetic in volunteers driven to the end point of their cardiovascular stability may delay the onset of orthostatic syncope. We investigated this in healthy male subjects. Each subject underwent a head up tilt (HUT) + graded lower body negative pressure (LBNP) up to presyncope session (control) to determine the orthostatic tolerance time, OTT (Time from HUT commencement to development of presyncopal symptoms/signs). Once the tolerance time was known, a randomized crossover protocol was used: either 1) Repeat HUT + LBNP to ensure reproducibility of repeated run or 2) HUT + LBNP run but with added mental challenge (two min before the expected presyncope time). Test protocols were separated by two weeks. Our studies on five male test subjects indicate that mental challenge improves orthostatic tolerance significantly. Additional mental loading could be a useful countermeasure to alleviate the orthostatic responses of persons, particularly in those with histories of dizziness on standing up, or to alleviate hypotension that frequently occurs during hemodialysis or on return to earth from the spaceflight environment of microgravity.

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Costa, F.; Furlan, R.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1999-01-01

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.

Orthostatic hypotension and association of arterial compliance in elderly patients with hypertension: a pilot study.

PubMed

Toba, Ayumi; Ishikawa, Joji; Harada, Kazumasa

2017-10-01

Orthostatic hypotension (OH) is associated with cardiovascular diseases, heart failure, and increased mortality. We evaluated whether OH was affected by cardiac structure and function or autonomic function in elderly hypertensive outpatients. In 64 hypertension patients (mean age 74.2±1.7 years old), we evaluated changes in blood pressure (BP) and heart rate variability before and after standing up using the MemCalc system. In addition, we retrospectively reviewed their medical records and echocardiographic data. Of the total patients, 28% had OH [decrease of systolic blood pressure (SBP) ≥20 mmHg and/or diastolic BP ≥10 mmHg]. Multivariate linear regression analysis showed that stroke volume (SV)/pulse pressure (PP) was associated independently with orthostatic change in SBP (P=0.007). The patients with OH tended to have a lower SV (57.3±13.1 vs. 68.1±16.3 ml, P=0.009) and lower SV/PP (1.02±0.26 vs. 1.33±0.45, P=0.001) than those without OH. The significance in difference in SV/PP remained even after adjustment for age, sex, BMI, estimated glomerular filtration rate, number of antihypertesive drugs, history of diabetes, and SBP at rest (P=0.036). However, there were no significant differences in change in the low frequency/high frequency ratio after standing up (P=0.899) between patients with and without OH. Elderly hypertensive patients with OH may have a reduced arterial compliance, measured as SV/PP, and may not have differences in sympathetic nerve activities, measured as the low frequency/high frequency ratio.

[Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study].

PubMed

Hempel, Bernd; Kroll, Michael; Schneider, Berthold

2005-01-01

Korodin Herz-Kreislauf-Tropfen, a herbal drug containing D-camphor (CAS 76-22-2; 2.5 %) and a liquid extract of fresh hawthorn berries (97.3%), has been used since many years for the treatment of orthostatic hypotension. The combination as well as its constituents were tested in clinical trials against placebo with healthy volunteers and patients using tilt-tests. The objective of this study was to investigate efficacy and safety of the drug under the conditions of medical practice in comparison to other drugs admitted for this indication. The study was performed as an epidemiological retrospective cohort study in 46 medical practices in Germany. In the practices the files were reviewed for patients who were treated between 1st January 2000 and 31st December 2002 for orthostatic hypotension. Included in the study were all patients who were treated either with the test drug or a control drug containing etilefrine, oxilofrine, midodrine, norfenefrine or dihydroergotamine and who met the inclusion criteria. The data of the files were coded, transferred to case report forms and augmented by the physician's statements about symptoms and success. Effect criteria were the improvement of symptoms and change of blood pressure during treatment. The correctness of the data was controlled using anonymous copies of the files. A total of 490 patients (399 in the test-group and 91 in the control group) between 11 and 102 years were included in the study. To correct heterogeneities in baseline conditions, treatment results were adjusted by regression and stratification to equal baseline conditions using the propensity score. The adjusted odds ratio for improvement was 5.6, the adjusted mean increase of the systolic blood pressure the 2-fold compared to the control group. The difference was highly significant and did not depend on age or initial blood pressure. In the test group two adverse events were observed which had no relation to the medication; in the control group one

Electrical stimulation-evoked contractions blunt orthostatic hypotension in sub-acute spinal cord-injured individuals: two clinical case studies.

PubMed

Hamzaid, N A; Tean, L T; Davis, G M; Suhaimi, A; Hasnan, N

2015-05-01

Prospective study of two cases. To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)). University Malaya Medical Centre, Kuala Lumpur, Malaysia. A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects' blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded. Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min). Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals.

Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Black, B.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1997-01-01

BACKGROUND: Idiopathic orthostatic tachycardia (IOT) is characterized by an increase in heart rate (HR) with standing of > or = 30 bpm that is associated with elevated catecholamine levels and orthostatic symptoms. A dynamic orthostatic hypovolemia and alpha1-adrenoreceptor hypersensitivity have been demonstrated in IOT patients. There is evidence of an autonomic neuropathy affecting the lower-extremity blood vessels. METHODS AND RESULTS: We studied the effects of placebo, the alpha1-adrenoreceptor agonist midodrine (5 to 10 mg), the alpha2-adrenoreceptor agonist clonidine (0.1 mg), and I.V. saline (1 L) in 13 patients with IOT. Supine and upright blood pressure (BP) and HR were measured before and at 1 and 2 hours after intervention. Midodrine decreased both supine and upright HR (all HR values are given as bpm) at 2 hours (from 78+/-2 supine to 108+/-5 upright before treatment and from 69+/-2 supine to 95+/-5 upright after treatment, P<.005 for supine and P<.01 for upright). Saline decreased both supine and upright HR (from 80+/-3 supine to 112+/-5 upright before infusion and from 77+/-3 supine to 91+/-3 upright 1 hour after infusion, P<.005 for supine and P<.001 for upright). Clonidine decreased supine HR (from 78+/-2 to 74+/-2, P<.03) but did not affect the HR increase with standing. Clonidine very significantly decreased supine systolic BP (from 109+/-3 at baseline to 99+/-2 mm Hg at 2 hours, P<.001), and midodrine decreased supine systolic BP mildly. CONCLUSIONS: IOT responds best acutely to saline infusion to correct the underlying hypovolemia. Chronically, this can be accomplished with increased salt and water intake in conjunction with fludrocortisone. The response of patients to the alpha1-agonist midodrine supports the hypothesis of partial dysautonomia and indicates that the use of alpha1-agonists to pharmacologically replace lower-extremity postganglionic sympathetics is an appropriate overall goal of therapy. These findings are consistent with our

Refractory orthostatic hypotension in a patient with a spinal cord injury: Treatment with droxidopa.

PubMed

Canosa-Hermida, Eva; Mondelo-García, Cristina; Ferreiro-Velasco, María Elena; Salvador-de la Barrera, Sebastián; Montoto-Marqués, Antonio; Rodríguez-Sotillo, Antonio; Vizoso-Hermida, José Ramón

2018-01-01

Orthostatic hypotension (OH) is a common complication in patients with a spinal cord injury, mainly affecting complete injuries above neurological level T6. It is generally more severe during the acute phase but can remain symptomatic for several years. A 65-year-old male with a grade ASIA A post-traumatic cervical spinal cord injury, at neurological level C4, presenting with symptomatic refractory OH. Increased blood pressure (BP) levels and an overall clinical improvement was observed after administering an increasing dose of droxidopa. Treatment was started at a dose of 100 mg twice daily (bid), one to be taken upon rising in the morning and another one in the afternoon, at least three hours before bedtime. According to the patient's symptomatic response, each individual dose was increased by 100 mg at 48-hour intervals. Both increased mean BP levels and a subjective symptomatic improvement were evidenced at a dose of 300 mg bid. Treatment with droxidopa increases BP levels and improves symptoms related to refractory OH using all physical and pharmacological measures available. It could therefore constitute an effective alternative treatment for OH in patients with a spinal cord injury.

Post-spaceflight orthostatic intolerance: possible relationship to microgravity-induced plasticity in the vestibular system

NASA Technical Reports Server (NTRS)

Yates, B. J.; Kerman, I. A.

1998-01-01

Even after short spaceflights, most astronauts experience at least some postflight reduction of orthostatic tolerance; this problem is severe in some subjects. The mechanisms leading to postflight orthostatic intolerance are not well-established, but have traditionally been thought to include the following: changes in leg hemodynamics, alterations in baroreceptor reflex gain, decreases in exercise tolerance and aerobic fitness, hypovolemia, and altered sensitivity of beta-adrenergic receptors in the periphery. Recent studies have demonstrated that signals from vestibular otolith organs play an important role in regulating blood pressure during changes in posture in a 1-g environment. Because spaceflight results in plastic changes in the vestibular otolith organs and in the processing of inputs from otolith receptors, it is possible that another contributing factor to postflight orthostatic hypotension is alterations in the gain of vestibular influences on cardiovascular control. Preliminary data support this hypothesis, although controlled studies will be required to determine the relationship between changes in the vestibular system and orthostatic hypotension following exposure to microgravity. Copyright 1998 Elsevier Science B.V.

Orthostatic side effects of clomipramine and moclobemide during treatment for depression.

PubMed

Stage, Kurt Bjerregaard Bjerregaard

2005-01-01

From a clinical point of view, orthostatic hypotension is a significant side effect during antidepressant treatment, particularly in the case of tricyclic antidepressants (TCAs). This prospective, randomized clinical trial evaluated the effects of clomipramine and moclobemide on orthostatic blood pressure during treatment for depression. One hundred and fifteen depressed inpatients, age up to 70 years, were randomized to treatment with either moclobemide (400 mg/day) or clomipramine (150 mg/day) after 1 week of placebo treatment. Orthostatic blood pressure was measured weekly over the 6-week study period. Clomipramine, but not moclobemide, caused a statistically significant fall in systolic (F = 9.37, P = 0.0037) and diastolic orthostatic blood pressure (F = 3.74, P = 0.0017). In the clomipramine-treated group of patients, we found no correlation between subjective complaints of orthostatic dizziness and the size of systolic orthostatic blood pressure. In conclusion, this study indicates that moclobemide does not induce orthostatic side effects, which is a significant problem in treatment with TCAs. However, the choice of antidepressants depends on other factors as well, e.g. the therapeutic efficacy.

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

NASA Technical Reports Server (NTRS)

Gaffney, F. A.

1987-01-01

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

Spacelab life sciences flight experiments. An integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

NASA Astrophysics Data System (ADS)

Gaffney, F. Andrew

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 (CO 2 and C 2H 2 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

Clinical treatment of orthostatic hypotension after spinal cord injury with training based on electric uprise bed coupled with remote ECG and BP monitor.

PubMed

Shen, Dantong; Huang, Huai; Yuan, Hui; Zhang, Xu; Li, Min

2014-12-22

The treatment for orthostatic hypotension (OH) after spinal cord injury (SCI) is an important part of rehabilitation in late-stage SCI. Electric uprise bed training is a relatively commonly used method in treating OH, and how to carry out uprise bed training safely and effectively is an urgent problem. In the early stage of SCI, we used a remote monitoring system to monitor the whole process of uprise bed training, and we explored a safe and efficient method of electric uprise bed training. The experimental group consisted of 36 patients diagnosed with orthostatic hypotension (OH) after SCI and who received training with an electric uprise bed coupled with remote monitoring system, and the control group of 18 subjects who used a traditional training method. There were no differences in baseline data between the 2 groups. There were no severe symptoms during training in the experimental group, but 3 patients had severe symptoms in the control group. Among the 32 enrolled subjects reaching upright training status within 30 days (17 subjects in the experimental group and 15 subjects in the control group), time interval of training from horizontal position to erect position in the experimental group was 18.00±3.12 days and 21.40±4.95 days in the control group. Time interval in the experimental group was significantly less than in the control group. However, among all 36 subjects, by combining results of follow-up, there was no significant difference of time interval of training from horizontal position to erect position between the experimental group and the control group. In the experimental group 90.52% of patients finished training compared to 78.19% in the control group (P<0.01). After training, values of OCs and OCd of the experimental group were lower than in the control group. There was no significant difference between groups in number of re-diagnosed OH. Implementation of training with electric uprise bed coupled with remote monitoring system is generally

Robotic tilt table reduces the occurrence of orthostatic hypotension over time in vegetative states.

PubMed

Taveggia, Giovanni; Ragusa, Ivana; Trani, Vincenzo; Cuva, Daniele; Angeretti, Cristina; Fontanella, Marco; Panciani, Pier Paolo; Borboni, Alberto

2015-06-01

The aim of this study is to evaluate the effects of verticalization with or without combined movement of the lower limbs in patients in a vegetative state or a minimally conscious state. In particular, we aimed to study whether, in the group with combined movement, there was better tolerance to verticalization. This was a randomized trial conducted in a neurorehabilitation hospital. Twelve patients with vegetative state and minimally conscious state 3-18 months after acute acquired brain injuries were included. Patients were randomized into A and B treatment groups. Study group A underwent verticalization with a tilt table at 65° and movimentation of the lower limbs with a robotic system for 30 min three times a week for 24 sessions. Control group B underwent the same rehabilitation treatment, with a robotic verticalization system, but an inactive lower-limb movement system. Systolic and diastolic blood pressure and heart rate were determined. Robotic movement of the lower limbs can reduce the occurrence of orthostatic hypotension in hemodynamically unstable patients. Despite the small number of patients involved (only eight patients completed the trial), our results indicate that blood pressures and heart rate can be stabilized better (with) by treatment with passive leg movements in hemodynamically unstable patients.

Risk Factors for Orthostatic Hypotension: Differences Between Elderly Men and Women.

PubMed

Méndez, Andrea S; Melgarejo, Jesús D; Mena, Luis J; Chávez, Carlos A; González, Alicex C; Boggia, José; Terwilliger, Joseph D; Lee, Joseph H; Maestre, Gladys E

2018-06-11

Orthostatic hypotension (OH) occurs when mechanisms regulating blood pressure (BP) levels after standing-up are altered. It is unclear how prevalence and risk factors for OH are different between sexes. We aimed to investigate sex differences in prevalence and risk factors for OH elderly individuals. We included 882 participants from Maracaibo Aging Study. OH was a sustained reduction of ≥20 mm Hg in systolic BP, ≥10 mm Hg in diastolic BP, or both, after 3 minutes of changing positions from supine to standing. Multivariable logistic regression models were used to examine the relationships among risk factors for OH in men and women considering interaction sex-term and stratified by sex. The mean age was 66.7 ± 8.5 years, being similar by sex. Women and men 55-74 years had similar prevalence of OH+ (18.5% vs. 20.9%, respectively). After 75 years, the proportion of women with OH+ was lower than men (11% vs. 30%, respectively). Hypertension, specifically systolic BP ≥140 mm Hg, and high pulse pressure (PP) were related with OH+ accounted by interaction sex-term, while diastolic BP ≥90 mm Hg, antihypertensive treatment, body mass index (BMI), diabetes mellitus and age were not. Systolic BP ≥140 mm Hg increases the risk of OH only among women, while BMI showed an inverse association in both sexes. Although the prevalence of OH is similar in both sexes, there are different risk factors associated by sex. Systolic BP ≥140 mm Hg was associated with increased risk of OH only with women while BMI was a protective factor for OH in men and women.

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

NASA Technical Reports Server (NTRS)

Low, P. A.; Novak, V.; Spies, J. M.; Novak, P.; Petty, G. W.

1999-01-01

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

PubMed Central

Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

2001-01-01

OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

Implication of altered autonomic control for orthostatic tolerance in SCI.

PubMed

Wecht, Jill Maria; Bauman, William A

2018-01-01

Neural output from the sympathetic and parasympathetic branches of the autonomic nervous system (ANS) are integrated to appropriately control cardiovascular responses during routine activities of daily living including orthostatic positioning. Sympathetic control of the upper extremity vasculature and the heart arises from the thoracic cord between T1 and T5, whereas splanchnic bed and lower extremity vasculature receive sympathetic neural input from the lower cord between segments T5 and L2. Although the vasculature is not directly innervated by the parasympathetic nervous system, the SA node is innervated by post-ganglionic vagal nerve fibers via cranial nerve X. Segmental differences in sympathetic cardiovascular innervation highlight the effect of lesion level on orthostatic cardiovascular control following spinal cord injury (SCI). Due to impaired sympathetic cardiovascular control, many individuals with SCI, particularly those with lesions above T6, are prone to orthostatic hypotension (OH) and orthostatic intolerance (OI). Symptomatic OH, which may result in OI, is a consequence of episodic reductions in cerebral perfusion pressure and the symptoms may include: dizziness, lightheadedness, nausea, blurred vision, ringing in the ears, headache and syncope. However, many, if not most, individuals with SCI who experience persistent and episodic hypotension and OH do not report symptoms of cerebral hypoperfusion and therefore do not raise clinical concern. This review will discuss the mechanism underlying OH and OI following SCI, and will review our knowledge to date regarding the prevalence, consequences and possible treatment options for these conditions in the SCI population. Published by Elsevier B.V.

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

PubMed

Rowe, P C; Barron, D F; Calkins, H; Maumenee, I H; Tong, P Y; Geraghty, M T

1999-10-01

To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

Lack of causal association between spontaneous intracranial hypotension and cranial cerebrospinal fluid leaks.

PubMed

Schievink, Wouter I; Schwartz, Marc S; Maya, M Marcel; Moser, Franklin G; Rozen, Todd D

2012-04-01

Spontaneous intracranial hypotension is an important cause of headaches and an underlying spinal CSF leak can be demonstrated in most patients. Whether CSF leaks at the level of the skull base can cause spontaneous intracranial hypotension remains a matter of controversy. The authors' aim was to examine the frequency of skull base CSF leaks as the cause of spontaneous intracranial hypotension. Demographic, clinical, and radiological data were collected from a consecutive group of patients evaluated for spontaneous intracranial hypotension during a 9-year period. Among 273 patients who met the diagnostic criteria for spontaneous intracranial hypotension and 42 who did not, not a single instance of CSF leak at the skull base was encountered. Clear nasal drainage was reported by 41 patients, but a diagnosis of CSF rhinorrhea could not be established. Four patients underwent exploratory surgery for presumed CSF rhinorrhea. In addition, the authors treated 3 patients who had a postoperative CSF leak at the skull base following the resection of a cerebellopontine angle tumor and developed orthostatic headaches; spinal imaging, however, demonstrated the presence of a spinal source of CSF leakage in all 3 patients. There is no evidence for an association between spontaneous intracranial hypotension and CSF leaks at the level of the skull base. Moreover, the authors' study suggests that a spinal source for CSF leakage should even be suspected in patients with orthostatic headaches who have a documented skull base CSF leak.

[Orthostatic postural tachycardia: study of 8 patients].

PubMed

Santiago Pérez, S; Ferrer Gila, T

1998-02-07

The occurrence of syncopal episodes is a very frequent event. In the absence of a structural systemic or cardiac disease, syncope is resulting of an anomalous cardiovascular response neurally mediated by the autonomic nervous system. It is the final common manifestation of different abnormal mechanisms and is frequently precipitated by orthostatism. Orthostatic intolerance syndrome refers to the development of symptoms during the upright posture that disappear in supine position. Tachycardia may be one of the clinical features of the syndrome. During orthostatic stress a hyperadrenergic response, with maintained increment of heart rate and associated symptoms, is developed. Changes in blood pressure may be diverse and in some cases hypotension and syncope occurs. Eight patients with symptoms of orthostatic intolerance who underwent autonomic evaluation and were diagnosed from postural tachycardia are presented. In all the cases an abnormal increment of heart rate during tilting was found and it was associated to hyperadrenergic symptoms. Evidence of restricted sympathetic impairment was observed in six cases with distal reduction of sudomotor function and abnormal adrenergic response during Valsalva manoeuvre. Symptoms disappeared or mostly subsided with pharmacological (amitriptyline in one case, phenobarbital in another one and non-cardioselective beta-blockers in six patients) and non-pharmacological treatment. In further examinations heart rate and blood pressure were normal.

Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Shea, J. D.; Doerr, D. F.; Convertino, V. A.

1992-01-01

To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid-cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg).

Postural Orthostatic Tachycardia Syndrome and Its Unusual Presenting Complaints in Women: A Literature Minireview

PubMed Central

Sohail, Wafa; Hatipoglu, Betul; Wilson, Robert

2018-01-01

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system that is defined by symptoms of orthostatic intolerance. According to the current criteria for adults, currently, POTS is defined as a heart rate increment of 30 beats/minute or more after 10 minutes of standing in the absence of orthostatic hypotension. There is a vast majority that remains misdiagnosed due to the heterogeneity of the disorder. Due to a lack of Food and Drug Administration (FDA) approved therapy, alternative therapies and over the counter medications are used to alleviate the symptoms. This is an uncommon presentation observed primarily in women, as it is more prevalent in females. PMID:29876157

Midodrine prevents orthostatic intolerance associated with simulated spaceflight

NASA Technical Reports Server (NTRS)

Ramsdell, C. D.; Mullen, T. J.; Sundby, G. H.; Rostoft, S.; Sheynberg, N.; Aljuri, N.; Maa, M.; Mukkamala, R.; Sherman, D.; Toska, K.;

Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

PubMed

Ramsdell, C D; Mullen, T J; Sundby, G H; Rostoft, S; Sheynberg, N; Aljuri, N; Maa, M; Mukkamala, R; Sherman, D; Toska, K; Yelle, J; Bloomfield, D; Williams, G H; Cohen, R J

2001-06-01

Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.

Graded Association Between Kidney Function and Impaired Orthostatic Blood Pressure Stabilization in Older Adults.

PubMed

Canney, Mark; O'Connell, Matthew D L; Sexton, Donal J; O'Leary, Neil; Kenny, Rose Anne; Little, Mark A; O'Seaghdha, Conall M

2017-05-04

Impaired orthostatic blood pressure (BP) stabilization is highly prevalent in older adults and is a predictor of end-organ injury, falls, and mortality. We sought to characterize the relationship between postural BP responses and the kidney. We performed a cross-sectional analysis of 4204 participants from The Irish Longitudinal Study on Ageing, a national cohort of community-dwelling adults aged ≥50 years. Beat-to-beat systolic and diastolic BP were measured during a 2-minute active stand test. The primary predictor was cystatin C estimated glomerular filtration rate (eGFR) categorized as follows (mL/min per 1.73 m 2 ): ≥90 (reference, n=1414); 75 to 89 (n=1379); 60 to 74 (n=942); 45 to 59 (n=337); <45 (n=132). We examined the association between eGFR categories and (1) sustained orthostatic hypotension, defined as a BP drop exceeding consensus thresholds (systolic BP drop ≥20 mm Hg±diastolic BP drop ≥10 mm Hg) at each 10-second interval from 60 to 110 seconds inclusive; (2) pattern of BP stabilization, characterized as the difference from baseline in mean systolic BP/diastolic BP at 10-second intervals. The mean age of subjects was 61.6 years; 47% of subjects were male, and the median eGFR was 82 mL/min per 1.73 m 2 . After multivariable adjustment, participants with eGFR <60 mL/min per 1.73 m 2 were approximately twice as likely to have sustained orthostatic hypotension ( P =0.008 for trend across eGFR categories). We observed a graded association between eGFR categories and impaired orthostatic BP stabilization, particularly within the first minute of standing. We report a novel, graded relationship between diminished eGFR and impaired orthostatic BP stabilization. Mapping the postural BP response merits further study in kidney disease as a potential means of identifying those at risk of hypotension-related events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Postprandial hypotension in older survivors of critical illness.

PubMed

Nguyen, Thu Anh Ngoc; Ali Abdelhamid, Yasmine; Weinel, Luke M; Hatzinikolas, Seva; Kar, Palash; Summers, Matthew J; Phillips, Liza K; Horowitz, Michael; Jones, Karen L; Deane, Adam M

2018-06-01

In older people postprandial hypotension occurs frequently; and is an independent risk factor for falls, cardiovascular events, stroke and death. The primary aim of this pilot study was to estimate the frequency of postprandial hypotension and evaluate the mechanisms underlying this condition in older survivors of an Intensive Care Unit (ICU). Thirty-five older (>65 years) survivors were studied 3 months after discharge. After an overnight fast, participants consumed a 300 mL drink containing 75 g glucose, labelled with 20 MBq 99m Tc-calcium phytate. Patients had concurrent measurements of blood pressure, heart rate, blood glucose and gastric emptying following drink ingestion. Proportion of participants is presented as percent (95% CI) and continuous variables as mean (SD). Postprandial hypotension was evident in 10 (29%; 95% CI 14-44), orthostatic hypotension in 2 (6%; 95% CI 0-13) and cardiovascular autonomic dysfunction in 2 (6%; 95% CI 0-13) participants. The maximal postprandial nadir for systolic blood pressure and diastolic blood pressures were -29 (14) mmHg and -18 (7) mmHg. In this cohort of older survivors of ICU postprandial hypotension occurred frequently . This suggests that postprandial hypotension is an unrecognised issue in older ICU survivors. Copyright © 2018. Published by Elsevier Inc.

Effects of water drinking on cardiovascular responses to supine exercise and on orthostatic hypotension after exercise in pure autonomic failure.

PubMed

Humm, A M; Mason, L M; Mathias, C J

2008-10-01

Patients with pure autonomic failure (PAF) have an abnormal fall in blood pressure (BP) with supine exercise and exacerbation of orthostatic hypotension (OH) after exercise. This study assessed the pressor effect of water on the cardiovascular responses to supine exercise and on OH after exercise. 8 patients with PAF underwent a test protocol consisting of standing for 5 min, supine rest for 10 min, supine exercise by pedalling a cycle ergometer at workloads of 25, 50 and 75 W (each for 3 min), supine rest for 10 min and standing for 5 min. The test protocol was performed without water ingestion and on a separate occasion after 480 ml of distilled water immediately after pre-exercise standing. Beat to beat cardiovascular indices were measured with the Portapres II device with subsequent Modelflow analysis. All patients had severe OH pre-exercise (BP fall systolic 65.0 (26.1) mm Hg, diastolic 22.7 (13.5) mm Hg), with prompt recovery of BP in the supine position. 5 min after water drinking, there was a significant rise in BP in the supine position. With exercise, there was a clear fall in BP (systolic 42.1 (24.4) mm Hg, diastolic 25.9 (10.0) mm Hg) with a modest rise in heart rate; this occurred even after water ingestion (BP fall systolic 49.8 (18.9) mm Hg, diastolic 26.0 (9.1) mm Hg). BP remained low after exercise but was significantly higher after water intake, resulting in better tolerance of post-exercise standing. Water drinking did not change the abnormal cardiovascular responses to supine exercise. However, water drinking improved orthostatic tolerance post-exercise.

Using the autonomic standards to assess orthostatic hypotension in persons with SCI: a case series.

PubMed

Wecht, Jill M; Wilson, James; Previnaire, Jean-Gabriel

2017-01-01

Spinal cord injury (SCI) creates a complex and unique syndrome of medical issues related to disruption of somatic and autonomic pathways. Among these impaired control of blood pressure (BP) can significantly impede patients' activities of daily living. The International Standards for the Assessment of Autonomic Function after SCI (ISAFSCI) is used to document the impact of SCI on resting BP (abnormal if below 90 mmHg) and the presence or absence of orthostatic hypotension (OH), defined as a symptomatic or asymptomatic decrease in BP (>/=20/10 mmHg) upon moving to an upright position. Case 1 documents the adverse influence of prescribed medications (antidepressants for neuropathic pain) on OH; case 2 describes the influence of bladder management on cardiovascular instability (autonomic dysreflexia and subsequent OH); case 3 describes the association between spasticity and OH; case 4 describes OH associated with a Valsalva maneuver. Impaired control of BP can stem from a combination of medical issues and autonomic dysfunction in persons with SCI. Management strategies for OH will vary depending on the stage of the SCI, the root cause of the OH and other confounding medical conditions. Non-pharmacological treatment should be considered as a first line of intervention and consideration should be given to cessation of potentially contributory medications prior to implementing pharmaceutical interventions. The systematic use of ISAFSCI by clinicians is recommended to document BP irregularities and to describe the effects of treatment strategies aimed at improving BP control in the SCI population.

Orthostatic hypotension: prevalence and associated risk factors among the ambulatory elderly in an Asian population

PubMed Central

Zhu, Qing Olivia; Tan, Choon Seng Gilbert; Tan, Hwee Leong; Wong, Ruining Geraldine; Joshi, Chinmaya Shrikant; Cuttilan, Ravi Amran; Sng, Gek Khim Judy; Tan, Ngiap Chuan

2016-01-01

INTRODUCTION The prevalence of orthostatic hypotension (OH) among the elderly population in Singapore, as defined by a decline in blood pressure upon a change in position, is not well-established. Studies associate OH with clinically significant outcomes such as falls. This study aims to determine the prevalence of OH among elderly patients attending a public primary care clinic (polyclinic) for chronic disease management, and examine the relationships between postulated risk factors and OH. METHODS Patients aged ≥ 65 years attending a typical polyclinic in Geylang were identified and targeted for recruitment at the study site. A questionnaire on symptoms and postulated risk factors was administered, followed by supine and standing blood pressure measurements. Cross-sectional analysis was performed with independent sample t-test for continuous data and chi-square test for categorical data. Prevalence rate ratios with 95% confidence interval were calculated for the latter. RESULTS A total of 364 multiethnic patients participated in the study. The prevalence of OH was 11.0%. Older age, comorbidities such as cardiac failure and kidney disease, being physically inactive at work, fatigue, self-reported dizziness in the past year, and the use of loop diuretics were found to be significantly associated with OH. CONCLUSION About one in ten elderly patients at a local polyclinic was affected by OH, which was associated with multiple factors. Some of these factors are modifiable and can be addressed to reduce the incidence of OH. PMID:27549316

Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension

PubMed Central

Higgins, Nicholas; Trivedi, Rikin; Greenwood, Richard; Pickard, John

2015-01-01

Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause. PMID:26251803

Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension.

PubMed

Higgins, Nicholas; Trivedi, Rikin; Greenwood, Richard; Pickard, John

2015-07-01

Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause.

The impact of arm position on the measurement of orthostatic blood pressure.

PubMed

Guss, David A; Abdelnur, Diego; Hemingway, Thomas J

2008-05-01

Blood pressure is a standard vital sign in patients evaluated in an Emergency Department. The American Heart Association has recommended a preferred position of the arm and cuff when measuring blood pressure. There is no formal recommendation for arm position when measuring orthostatic blood pressure. The objective of this study was to assess the impact of different arm positions on the measurement of postural changes in blood pressure. This was a prospective, unblinded, convenience study involving Emergency Department patients with complaints unrelated to cardiovascular instability. Repeated blood pressure measurements were obtained using an automatic non-invasive device with each subject in a supine and standing position and with the arm parallel and perpendicular to the torso. Orthostatic hypotension was defined as a difference of >or= 20 mm Hg systolic or >or= 10 mm Hg diastolic when subtracting standing from supine measurements. There were four comparisons made: group W, arm perpendicular supine and standing; group X, arm parallel supine and standing; group Y, arm parallel supine and perpendicular standing; and group Z, arm perpendicular supine and parallel standing. There were 100 patients enrolled, 55 men, mean age 44 years. Four blood pressure measurements were obtained on each patient. The percentage of patients meeting orthostatic hypotension criteria in each group was: W systolic 6% (95% CI 1%, 11%), diastolic 4% (95% CI 0%, 8%), X systolic 8% (95% CI 3%, 13%), diastolic 9% (95% CI 3%, 13%), Y systolic 19% (95% CI 11%, 27%), diastolic 30% (95% CI 21%, 39%), Z systolic 2% (95% CI 0%, 5%), diastolic 2% (95% CI 0%, 5%). Comparison of Group Y vs. X, Z, and W was statistically significant (p < 0.0001). Arm position has a significant impact on determination of postural changes in blood pressure. The combination of the arm parallel when supine and perpendicular when standing may significantly overestimate the orthostatic change. Arm position should be held

Continuous noninvasive orthostatic blood pressure measurements and their relationship with orthostatic intolerance, falls, and frailty in older people.

PubMed

Romero-Ortuno, Roman; Cogan, Lisa; Foran, Tim; Kenny, Rose Anne; Fan, Chie Wei

2011-04-01

To identify morphological orthostatic blood pressure (BP) phenotypes in older people and assess their correlation with orthostatic intolerance (OI), falls, and frailty and to compare the discriminatory performance of a morphological classification with two established orthostatic hypotension (OH) definitions: consensus (COH) and initial (IOH). Cross-sectional. Geriatric research clinic. Four hundred forty-two participants (mean age 72, 72% female) without dementia or risk factors for autonomic neuropathy. Active lying-to-standing test monitored using a continuous noninvasive BP monitor. For the morphological classification, four orthostatic systolic BP variables were extracted (delta (baseline - nadir) and maximum percentage of baseline recovered by 30 seconds and 1 and 2 minutes) using the 5-second averages method and entered in K-means cluster analysis (three clusters). Main outcomes were OI, falls (≥1 in past 6 months), and frailty (modified Fried criteria). The morphological clusters were small drop, fast overrecovery (n=112); medium drop, slow recovery (n=238); and large drop, nonrecovery (n=92). Their characterization revealed an increasing OI gradient (17.9%, 27.5%, and 44.6% respectively, P<.001) but no significant gradients in falls or frailty. The COH definition failed to reveal clinical differences between COH+ (n=416) and COH- (n=26) participants. The IOH definition resulted in a clinically meaningful separation between IOH+ (n=85) and IOH- (n=357) subgroups, as assessed according to OI (100% vs 11.5%, P<.001), falls (24.7% vs 10.4%, P<.001), and frailty (14.1% vs 5.4%, P=.005). It is recommended that the IOH definition be applied when taking continuous noninvasive orthostatic BP measurements in older people. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

PubMed

Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

2017-01-01

Background . Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods . The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results . Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

Midodrine hydrochloride and L-threo-3,4-dihydroxy-phenylserine preserve cerebral blood flow in hemodialysis patients with orthostatic hypotension.

PubMed

Fujisaki, Kiichiro; Kanai, Hidetoshi; Hirakata, Hideki; Nakamura, Sachiko; Koga, Yuko; Hattori, Fumitada; Iida, Mitsuo

2007-02-01

Orthostatic hypotension (OH) after hemodialysis (HD) is a serious complication, as it causes various neurological symptoms and even ischemic brain damage. The aim of the present study was to evaluate the effects of antihypotensive agents, midodrine hydrochloride (MID) and L-threo-3,4-dihydroxyphenylserine (L-DOPS), on OH after HD. We measured systolic blood pressure (SBP) and cerebral blood flow velocity in the middle cerebral artery (MCVm, by transcranial Doppler sonography), in patients with OH during a 5-min 60-degree head-up tilt test at both before and after 4-week treatment with MID at 4 mg/day (N = 6) or L-DOPS at 400 mg/day (N = 7). Both MID and L-DOPS did not significantly protect against falls in systolic BP (SBP) after passive head-up tilt. However, a significant improvement was achieved in MCVm-decrement in the MID group at 3 min and the L-DOPS group at 0, 1 and 3 min during head-up tilt. Although MID and L-DOPS did not prevent OH after HD in HD patients, both agents preserved cerebral blood flow during orthostasis in HD patients with OH.

Orthostatic hypotension in Parkinson disease: How much you fall or how low you go?

PubMed Central

Palma, Jose-Alberto; Gomez-Esteban, Juan Carlos; Kaufmann, Lucy; Martinez, Jose; Tijero, Beatriz; Berganzo, Koldo; Kaufmann, Horacio

2014-01-01

Background Orthostatic hypotension (OH) is frequent in patients with Parkinson disease (PD) and can occur with or without symptoms. Pharmacological treatments are effective but often exacerbate supine hypertension. Guidelines exist for the diagnosis but not for the treatment of OH. We examined the relationship between blood pressure and symptoms in a cohort of PD patients with the goal of identifying a hemodynamic target to guide treatment. Methods We measured blood pressure supine and upright (tilt or active standing) and identified the presence or absence of symptomatic OH by using a validated patient-reported outcome questionnaire in 210 patients with PD. We evaluated the usefulness of the 20/10 and 30/15 mmHg diagnostic criteria (systolic/diastolic) to identify symptomatic OH. Results Fifty percent of the PD patient cohort met criteria for the 20/10 fall and 30% for the 30/15 blood pressure fall. Among the patients who met either OH criteria, the percentage of those with symptoms was small (33% of those with 20/10 and 44% of those with 30/15 mmHg; 16% and 13%, respectively overall). Symptomatic OH was associated with an upright mean blood pressure below 75 mmHg. A mean standing blood pressure <75 mmHg had a sensitivity of 97% and a specificity of 98% for detecting symptomatic OH. Conclusions Although the prevalence of OH in PD is high, not all patients have symptoms of organ hypoperfusion. A mean standing blood pressure below 75 mmHg appears to be a useful benchmark when deciding whether the benefits of initiating pharmacological treatment of OH outweigh the risks of exacerbating supine hypertension. PMID:25678194

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Related to Hypoadrenergic Responsiveness

NASA Technical Reports Server (NTRS)

Meck, Janice V.; Platts, Steven H.; Waters, Wendy W.; Shi, Shang-Jin; Hayashi, Yuho; Perez, Sondra A.; Ziegler, Michael G.

2006-01-01

Circulating blood volume is reduced during spaceflight, making astronauts hemodynamically compromised. After landing, astronauts separate into two groups. One group compensates for the hypovolemia with a hyper-sympathetic response during upright tilt testing and can complete a tilt test with few symptoms. The other group is unable to mount a hyper-sympathetic response and experiences orthostatic hypotension and presyncope during upright tilt tests. We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, also would cause subjects to separate into presyncopal and non-presyncopal groups according to their sympathetic responses during tilt. We studied 20 subjects, including 10 veteran astronauts, on three occasions. On Days 1 (normovolemia) and 3 (hypovolemia), plasma volume, tilt tolerance and supine and standing plasma norepinephrine levels were measured. Forty hours prior to Day 3, subjects were given intravenous furosemide, followed by 36 hours of a 10MEq Na diet. Statistical comparisons were made between normovolemia and hypovolemia responses. This protocol reproduced landing day tilt test outcomes with 100% fidelity in the astronauts. Similarly to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 plus or minus 79 vs. 298 plus or minus 37 pg/ml, P less than 0.05), but presyncopal subjects had no increase (180 plus or minus 44 vs. 145 plus or minus 32 pg/ml, P=NS). This model can be used to predict astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. Within patient populations, it can be used to study the interaction of volemic state and the sympathetic nervous system.

The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder.

PubMed

Ehrminger, Mickael; Latimier, Alice; Pyatigorskaya, Nadya; Garcia-Lorenzo, Daniel; Leu-Semenescu, Smaranda; Vidailhet, Marie; Lehericy, Stéphane; Arnulf, Isabelle

2016-04-01

Idiopathic rapid eye movement sleep behaviour disorder is characterized by nocturnal violence, increased muscle tone during rapid eye movement sleep and the lack of any other neurological disease. However, idiopathic rapid eye movement sleep behaviour disorder can precede parkinsonism and dementia by several years. Using 3 T magnetic resonance imaging and neuromelanin-sensitive sequences, we previously found that the signal intensity was reduced in the locus coeruleus/subcoeruleus area of patients with Parkinson's disease and rapid eye movement sleep behaviour disorder. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex with neuromelanin-sensitive imaging in 21 patients with idiopathic rapid eye movement sleep behaviour disorder and compared the results with those from 21 age- and gender-matched healthy volunteers. All subjects underwent a clinical examination, motor, cognitive, autonomous, psychological, olfactory and colour vision tests, and rapid eye movement sleep characterization using video-polysomnography and 3 T magnetic resonance imaging. The patients more frequently had preclinical markers of alpha-synucleinopathies, including constipation, olfactory deficits, orthostatic hypotension, and subtle motor impairment. Using neuromelanin-sensitive imaging, reduced signal intensity was identified in the locus coeruleus/subcoeruleus complex of the patients with idiopathic rapid eye movement sleep behaviour. The mean sensitivity of the visual analyses of the signal performed by neuroradiologists who were blind to the clinical diagnoses was 82.5%, and the specificity was 81% for the identification of idiopathic rapid eye movement sleep behaviour. The results confirm that this complex is affected in idiopathic rapid eye movement sleep behaviour (to the same degree as it is affected in Parkinson's disease). Neuromelanin-sensitive imaging provides an early marker of non-dopaminergic alpha-synucleinopathy that can be detected on an individual

Orthostatic responses to dietary sodium restriction during heat acclimation

NASA Technical Reports Server (NTRS)

Szlyk, Patricia C.; Sils, Ingrid V.; Caretti, David M.; Moore, Robert J.; Armstrong, Lawrence E.; Tartarini, Kim A.; Francesconi, Ralph P.; Askew, Eldon W.; Hubbard, Roger W.

1994-01-01

Several studies have shown that individuals consuming low-salt diets and working in the heat have an increased risk or incidence of heat injury, suggestive of inadequate cardiovascular adjustment. Furthermore, others have shown that prolonged work in hot climates can precipitate orthostatic hypotension and syncope. This study was designed to evaluate the effects of moderate-salt (MS) and low-salt (LS) diets on the circulatory responses and incidence of presyncopal symptoms to an orthostatic test (OT) during successive days of heat acclimation (HA). Seventeen unacclimatized male soldiers (mean +/- SE: age 20+/-1 yrs) participated in this two-phase study. The first phase consisted of a seven day dietary stabilization period during which all subjects consumed similar diets of about 4000 kcal/day containing 8g NaCl and lived in a dormitory setting (21 C, 30% RH). The second phase commenced on day eight and consisted of dietary NaCl restriction and 10 days HA (days 8-17). Volunteers were randomly assigned to either the MS diet (n=9) providing 8g NaCl/day or the LS diet (n=8) furnishing just 4g NaCl/day. The acquisition of HA was manifested in both groups by reductions in exercising rectal temperature and heart rate (HR); these characteristics were similar in the MS and LS diets. The OT was performed at 21 C on day seven of the stabilization phase and on days 9, 11, 13, 15, and 17 of the HA phase, before and after 8.5 hr of intermittent treadmill walking in a hot environment. Blood pressure (BP) and HR responses at 1,2, and 4 min and any presyncopal symptoms were recorded after assuming an upright position from recumbency. All subjects completed the OT before and after prolonged exercise in the heat without incidence of either hypotension or presyncopal symptoms irrespective of dietary-salt intake and day of HA. The results indicate that the prolonged work in the heat can be performed without orthostatic hypotension or syncope while consuming 4g NaCl/day with adequate

Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France.

PubMed

Pathak, Atul; Raoul, Valérie; Montastruc, Jean-Louis; Senard, Jean-Michel

2005-07-01

The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple system atrophy, Lewy bodies disease) or secondary (diabetic and non-diabetic peripheral neuropathies) autonomic failure with symptomatic OH requiring pharmacological treatment with at least one drug marketed in France for OH were included together with six patients with refractory neurocardiogenic syncope. Of the patients, 85 received a monotherapy-mainly with midodrine (49.4%)-and 42 received various combinations, the association of midodrine and fludrocortisone being the most frequent (66.6%). Of all the 127 patients, 88 suffered from a total of 141 ADRs (1.60 per patient) with no statistical difference in ADR frequency between monotherapy and drug combinations (P>0.05). Among ADRs, 24 (17.0%) were considered as "serious" and 16 (11.3%) were considered as "unexpected", most of them observed with heptaminol. This study shows a high frequency of ADRs (especially serious and unexpected ADRs) with antihypotensive drugs. It strongly suggests the need for a better evaluation of the safety profile of antihypotensive drugs and improvement in summary of product characteristics.

Risk of Orthostatic Intolerance During Re-Exposure to Gravity

NASA Technical Reports Server (NTRS)

Platts, Steven; Stenger, Michael B.; Lee, Stuart M. C.; Westby, Christian M.; Phillips, Tiffany R.; Arzeno, Natalia M.; Johnston, Smith; Mulugeta, Lealem

2015-01-01

Post-spaceflight orthostatic intolerance remains a significant concern to NASA. In Space Shuttle missions, astronauts wore anti-gravity suits and liquid cooling garments to protect against orthostatic intolerance during re-entry and landing, but in-flight exercise and the end-of-mission fluid loading failed to protect approximately 30% of Shuttle astronauts when these garments were not worn. The severity of the problem appears to be increased after long-duration space flight. Five of six US astronauts could not complete a 10-minutes upright-posture tilt testing on landing day following 4-5 month stays aboard the Mir space station. The majority of these astronauts had experienced no problems of orthostatic intolerance following their shorter Shuttle flights. More recently, four of six US astronauts could not complete a tilt test on landing day following approximately 6 month stays on the International Space Station. Similar observations were made in the Soviet and Russian space programs, such that some cosmonauts wear the Russian compression garments (Kentavr) up to 4 days after landing. Future exploration missions, such as those to Mars or Near Earth Objects, will be long duration, and astronauts will be landing on planetary bodies with no ground-support teams. The occurrence of severe orthostatic hypotension could threaten the astronauts' health and safety and success of the mission.

Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence for sympathetic vasoconstriction

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Black, B. K.; Paranjape, S. Y.; Barwise, J.; Robertson, D.

1998-01-01

Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood flow associated with standing despite sustained systemic blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the hypothesis that volume loading (2000 cc normal saline) and alpha-adrenoreceptor agonism improve systemic hemodynamics and cerebral perfusion and that the decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by alpha-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume loading (-20+/-3.2 bpm) and phenylephrine (-18+/-3.4 bpm) significantly reduced upright heart rate compared with placebo; the effect was diminished at the end of HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20+/-3.7 bpm) and at the end of HUT (14+/-5 bpm). With placebo, mean cerebral blood flow velocity decreased by 33+/-6% at the end of HUT. This decrease in cerebral blood flow with HUT was attenuated by all 3 interventions. We conclude that in patients with IOI, HUT causes a substantial decrease in cerebrovascular blood flow velocity. The decrease in blood flow velocity with HUT can be attenuated with interventions that improve systemic hemodynamics and therefore decrease reflex sympathetic activation. Moreover, alpha-adrenoreceptor blockade also blunts the decrease in cerebral blood flow with HUT but at the price of deteriorated systemic hemodynamics. These observations may suggest that in patients with IOI, excessive sympathetic activity contributes to the paradoxical decrease in cerebral blood flow with upright posture.

Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia.

PubMed

Wecht, Jill M; Radulovic, Miroslav; Lafountaine, Michael F; Rosado-Rivera, Dwindally; Zhang, Run-Lin; Bauman, William A

2009-08-01

To determine the effects of 1.0 mg/kg nitro-L-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. Prospective placebo-controlled intervention study. James J. Peters Veterans Affairs Medical Center. Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22+/-14 years. Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0 mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45 degrees for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. Orthostatic MAP. Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69+/-11 vs 89+/-9 mmHg, respectively; P<.01) and compared with L-NAME infusion (90+/-16 mmHg; P<.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia.

The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus.

PubMed

Check, J H; Weidner, J

2015-01-01

To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

Space Flight Orthostatic Intolerance Protection

NASA Technical Reports Server (NTRS)

Luty, Wei

2009-01-01

This paper summarizes investigations conducted on different orthostatic intolerance protection garments. This paper emphasizes on the engineering and operational aspects of the project. The current Shuttle pneumatic Anti-G Suit or AGS at 25 mmHg (0.5 psi) and customized medical mechanical compressive garments (20-30 mmHg) were tested on human subjects. The test process is presented. The preliminary results conclude that mechanical compressive garments can ameliorate orthostatic hypotension in hypovolemic subjects. A mechanical compressive garment is light, small and works without external pressure gas source; however the current garment design does not provide an adjustment to compensate for the loss of mass and size in the lower torso during long term space missions. It is also difficult to don. Compression garments that do not include an abdominal component are less effective countermeasures than garments which do. An early investigation conducted by the Human Adaptation and Countermeasures Division at Johnson Space Center (JSC) has shown there is no significant difference between the protection function of the AGS (at 77 mmHg or 1.5 psi) and the Russian anti-g suit, Kentavr (at 25 mmHg or 0.5 psi). Although both garments successfully countered hypovolemia-induced orthostatic intolerance, the Kentavr provided protection by using lower levels of compression pressure. This more recent study with a lower AGS pressure shows that pressures at 20-30 mmHg is acceptable but protection function is not as effective as higher pressure. In addition, a questionnaire survey with flight crewmembers who used both AGS and Kentavr during different missions was also performed.

Cerebral versus systemic hemodynamics during graded orthostatic stress in humans

NASA Technical Reports Server (NTRS)

Levine, B. D.; Giller, C. A.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.

1994-01-01

BACKGROUND: Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hemodynamic collapse. Recent research in patients with neurocardiogenic syncope has suggested that cerebral vasoconstriction may occur during orthostatic hypotension, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. However, the regulation of cerebral blood flow (CBF) in such patients may be quite different from that of healthy individuals, particularly when assessed during the rapidly changing hemodynamic conditions associated with neurocardiogenic syncope. To be able to interpret the pathophysiological significance of these observations, a clear understanding of the normal responses of the cerebral circulation to orthostatic stress must be obtained, particularly in the context of the known changes in systemic and regional distributions of blood flow and vascular resistance during orthostasis. Therefore, the specific aim of this study was to examine the changes that occur in the cerebral circulation during graded reductions in central blood volume in the absence of systemic hypotension in healthy humans. We hypothesized that cerebral vasoconstriction would occur and CBF would decrease due to activation of the sympathetic nervous system. We further hypothesized, however, that the magnitude of this change would be small compared with changes in systemic or skeletal muscle vascular resistance in healthy subjects with intact autoregulation and would be unlikely to cause syncope without concomitant hypotension. METHODS AND RESULTS: To test this hypothesis, we studied 13 healthy men (age, 27 +/- 7 years) during progressive lower body negative pressure (LBNP). We measured systemic flow (Qc is cardiac output; C2H2 rebreathing), regional forearm flow (FBF; venous occlusion plethysmography), and blood pressure (BP; Finapres) and calculated systemic (SVR) and forearm (FVR) vascular resistances. Changes in brain blood flow were

Acute fluid ingestion in the treatment of orthostatic intolerance - important implications for daily practice.

PubMed

Z'Graggen, W J; Hess, C W; Humm, A M

2010-11-01

Rapid water ingestion improves orthostatic intolerance (OI) in multiple system atrophy (MSA) and postural tachycardia syndrome (PoTS). We compared haemodynamic changes after water and clear soup intake, the latter being a common treatment strategy for OI in daily practice. Seven MSA and seven PoTS patients underwent head-up tilt (HUT) without fluid intake and 30 min after drinking 450 ml of water and clear soup, respectively. All patients suffered from moderate to severe OI because of neurogenic orthostatic hypotension (OH) and excessive orthostatic heart rate (HR) increase, respectively. Beat-to-beat cardiovascular indices were measured non-invasively. In MSA, HUT had to be terminated prematurely in 2/7 patients after water, but in 6/7 after clear soup. At 3 min of HUT, there was an increase in blood pressure of 15.7(8.2)/8.3(2.3) mmHg after water, but a decrease of 11.6(18.9)/8.1(9.2) mmHg after clear soup (P < 0.05). In PoTS, HUT could always be completed for 10 min, but OI subjectively improved after both water and clear soup. The attenuation of excessive orthostatic HR increase did not differ significantly after water and clear soup drinking. In MSA, clear soup cannot substitute water for eliciting a pressor effect, but even worsens OI after rapid ingestion. In PoTS, acute water and clear soup intake both result in improvement of OI. These findings cannot solely be explained by difference in osmolarity but may reflect some degree of superimposed postprandial hypotension in widespread autonomic failure in MSA compared to the mild and limited autonomic dysfunction in PoTS. © 2010 The Author(s). Journal compilation © 2010 EFNS.

Audiovestibular impairments associated with intracranial hypotension.

PubMed

Choi, Jae-Hwan; Cho, Kee-Yong; Cha, Seung-Yi; Seo, Jae-Deuk; Kim, Min-Ji; Choi, Yu Ri; Kim, Sung-Hee; Kim, Ji-Soo; Choi, Kwang-Dong

2015-10-15

To investigate the patterns and mechanisms of audiovestibular impairments associated with intracranial hypotension. We had consecutively recruited 16 patients with intracranial hypotension at the Neurology Center of Pusan National University Hospital for two years. Spontaneous, gaze-evoked, and positional nystagmus were recorded using 3D video-oculography in all patients, and the majority of them also had pure tone audiometry and bithermal caloric tests. Of the 16 patients, five (31.3%) reported neuro-otological symptoms along with the orthostatic headache while laboratory evaluation demonstrated audiovestibular impairments in ten (62.5%). Oculographic analyses documented spontaneous and/or positional nystagmus in six patients (37.5%) including weak spontaneous vertical nystagmus with positional modulation (n=4) and pure positional nystagmus (n=2). One patient presented with recurrent spontaneous vertigo and tinnitus mimicking Meniere's disease, and showed unidirectional horizontal and torsional nystagmus with normal head impulse tests during the attacks. Bithermal caloric tests were normal in all nine patients tested. Audiometry showed unilateral (n=6) or bilateral (n=1) sensorineural hearing loss in seven (53.8%) of the 13 patients tested. Intracranial hypotension frequently induces audiovestibular impairments. In addition to endolymphatic hydrops and irritation of the vestibulocochlear nerve, compression or traction of the brainstem or cerebellum due to loss of CSF buoyancy may be considered as a mechanism of frequent spontaneous or positional vertical nystagmus in patients with intracranial hypotension. Copyright © 2015 Elsevier B.V. All rights reserved.

Contributions of MSNA and stroke volume to orthostatic intolerance following bed rest

NASA Technical Reports Server (NTRS)

Shoemaker, J. K.; Hogeman, C. S.; Sinoway, L. I.

1999-01-01

We examined whether the altered orthostatic tolerance following 14 days of head-down tilt bed rest (HDBR) was related to inadequate sympathetic outflow or to excessive reductions in cardiac output during a 10- to 15-min head-up tilt (HUT) test. Heart rate, blood pressure (BP, Finapres), muscle sympathetic nerve activity (MSNA, microneurography), and stroke volume blood velocity (SVV, Doppler ultrasound) were assessed during supine 30 degrees (5 min) and 60 degrees (5-10 min) HUT positions in 15 individuals who successfully completed the pre-HDBR test without evidence of orthostatic intolerance. Subjects were classified as being orthostatically tolerant (OT, n = 9) or intolerant (OI, n = 6) following the post-HDBR test. MSNA, BP, and SVV during supine and HUT postures were not altered in the OT group. Hypotension during 60 degrees HUT in the post-bed rest test for the OI group (P < 0.05) was associated with a blunted increase in MSNA (P < 0.05). SVV was reduced following HDBR in the OI group (main effect of HDBR, P < 0.02). The data support the hypothesis that bed rest-induced orthostatic intolerance is related to an inadequate increase in sympathetic discharge that cannot compensate for a greater postural reduction in stroke volume.

Blood pressure circadian rhythms and adverse outcomes in type 2 diabetes patients diagnosed with orthostatic hypotension.

PubMed

Chang, Jing; Hou, Yuan-Ping; Wu, Jin-Ling; Fang, Xiang-Yang; Li, Sheng-Li; Liu, Miao-Bing; Sun, Qian-Mei

2018-03-01

Patients with diabetes frequently develop orthostatic hypotension (OH). The present study was designed to examine the relationship of blood pressure (BP) circadian rhythms and outcomes in diabetes with OH. In the present study, 173 inpatients with type 2 diabetes were enrolled. Patients were divided into an OH group and a non-OH group according to the BP changes detected in the supine and standing position. Then, 24-h ambulatory BP was monitored. Patients were followed up for an average of 45 ± 10 months post-discharge. Outcomes - death and major adverse cardiac and cerebrovascular events, including heart failure, myocardial infarction and stroke - were recorded. There were 61 patients (35.26%) in the OH group and 112 patients (64.74%) in the non-OH group. In the OH group, the night-time systolic BP and night-time diastolic BP were higher, the blood BP rhythms were predominantly of the riser type (67.21%). OH was as an independent marker of riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval 2.579-7.966). In the OH group, the incidence rates of mortality, and major adverse cardiac and cerebrovascular events were increased significantly compared with those in the non-OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P < 0.01). In patients who had type 2 diabetes diagnosed with OH, the BP circadian rhythm usually showed riser patterns, and they had increased rates of mortality, and major adverse cardiac and cerebrovascular events. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Evidence for a functional cardiac interaction between losartan and angiotensin-(1–7) receptors revealed by orthostatic tilting test in rats

PubMed Central

Matos de Moura, Marina; Augusto Sousa dos Santos, Robson; Antônio Peliky Fontes, Marco

2005-01-01

Studies have shown that the angiotensin II (Ang II) AT1 receptor antagonist, losartan, accentuates the orthostatic hypotensive response in anesthetized rats, and there is evidence indicating that this effect is not exclusively mediated by AT1 receptors. We investigated whether the pronounced orthostatic cardiovascular response observed in losartan-treated rats involves an interference with angiotensin-(1–7) (Ang-(1–7)) receptors. Urethane-anesthetized rats were submitted to orthostatic stress (90° head-up tilt for 2 min). Intravenous injection of losartan (1 mg kg−1, n=9) significantly accentuated the decrease in mean arterial pressure (MAP) induced by head-up tilt (−33±6% after losartan vs −15±8% control tilt). This effect was accompanied by a significant bradycardia (−8±3% after losartan vs −3±3% control tilt). Another AT1 antagonist, candesartan, did not potentiate the decrease of MAP and did not change the cardiac response induced by head-up tilt. Strikingly, administration of the Ang-(1–7) antagonist, A-779 (10 nmol kg−1, n=5), totally reversed the bradicardiac effect caused by losartan and this effect was accompanied by a tendency towards attenuation of the hypotensive response caused by losartan. These findings indicate that the marked orthostatic cardiovascular response is specific for losartan, and that it may be due, in part, to an interaction of this antagonist with Ang-(1–7) receptors, probably at the cardiac level. PMID:15685215

Distribution and observed associations of orthostatic blood pressure changes in elderly general medicine outpatients

NASA Technical Reports Server (NTRS)

Robertson, D.; DesJardin, J. A.; Lichtenstein, M. J.

1998-01-01

Factors associated with orthostatic blood pressure change in elderly outpatients were determined by surveying 398 medical clinical outpatients aged 65 years and older. Blood pressure was measured with random-zero sphygmomanometers after patients were 5 minutes in a supine and 5 minutes in a standing position. Orthostatic blood pressure changes were at normally distributed levels with systolic and diastolic pressures dropping an average of 4 mm Hg (standard deviation [SD]=15 mm Hg) and 2 mm Hg (SD=11 mm Hg), respectively. Orthostatic blood pressure changes were unassociated with age, race, sex, body mass, time since eating, symptoms, or other factors. According to multiple linear regression analysis, supine systolic pressure, chronic obstructive pulmonary disease (COPD), and diabetes mellitus were associated with a decrease in systolic pressure on standing. Hypertension, antiarthritic drugs, and abnormal heartbeat were associated with an increase in systolic pressure on standing. For orthostatic diastolic pressure changes, supine diastolic pressure and COPD were associated with a decrease in diastolic pressure on standing. Congestive heart failure was associated with an increase in standing diastolic pressure. Using logistic regression analysis, only supine systolic pressure was associated with a greater than 20-mm Hg drop in systolic pressure (n=53, prevalence=13%). Supine diastolic pressure and COPD were the only variables associated with a greater than 20-mm Hg drop in diastolic pressure (n=16, prevalence=4%). These factors may help physicians in identifying older persons at risk for having orthostatic hypotension.

Familial orthostatic tachycardia due to norepinephrine transporter deficiency

NASA Technical Reports Server (NTRS)

Robertson, D.; Flattem, N.; Tellioglu, T.; Carson, R.; Garland, E.; Shannon, J. R.; Jordan, J.; Jacob, G.; Blakely, R. D.; Biaggioni, I.

2001-01-01

Orthostatic intolerance (OI) or postural tachycardia syndrome (POTS) is a syndrome primarily affecting young females, and is characterized by lightheadedness, palpitations, fatigue, altered mentation, and syncope primarily occurring with upright posture and being relieved by lying down. There is typically tachycardia and raised plasma norepinephrine levels on upright posture, but little or no orthostatic hypotension. The pathophysiology of OI is believed to be very heterogeneous. Most studies of the syndrome have focused on abnormalities in norepinephrine release. Here the hypothesis that abnormal norepinephrine transporter (NET) function might contribute to the pathophysiology in some patients with OI was tested. In a proband with significant orthostatic symptoms and tachycardia, disproportionately elevated plasma norepinephrine with standing, impaired systemic, and local clearance of infused tritiated norepinephrine, impaired tyramine responsiveness, and a dissociation between stimulated plasma norepinephrine and DHPG elevation were found. Studies of NET gene structure in the proband revealed a coding mutation that converts a highly conserved transmembrane domain Ala residue to Pro. Analysis of the protein produced by the mutant cDNA in transfected cells demonstrated greater than 98% reduction in activity relative to normal. NE, DHPG/NE, and heart rate correlated with the mutant allele in this family. CONCLUSION: These results represent the first identification of a specific genetic defect in OI and the first disease linked to a coding alteration in a Na+/Cl(-)-dependent neurotransmitter transporter. Identification of this mechanism may facilitate our understanding of genetic causes of OI and lead to the development of more effective therapeutic modalities.

Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies.

PubMed

Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio; Palma, Jose-Alberto; Shibao, Cyndya A; Biaggioni, Italo; Peltier, Amanda C; Singer, Wolfgang; Low, Phillip A; Goldstein, David S; Gibbons, Christopher H; Freeman, Roy; Robertson, David

2018-03-01

Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation. We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; -44 ± 25 vs -21 ± 14 mmHg [mean ± standard deviation], p < 0.0001) but only one-third of the increase in HR of those with nonneurogenic OH (8 ± 8 vs 25 ± 11 beats per minute [bpm], p < 0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve = 0.96, p < 0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p = 0.0003), but there was considerable overlap with patients with Lewy body disorders. A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio < 0.5 bpm/mmHg is diagnostic of neurogenic OH. Ann Neurol 2018;83:522-531. © 2018 American Neurological Association.

Therapeutic use of compression stockings for orthostatic hypotension: an assessment of patient and physician perspectives and practices.

PubMed

Quinn, Colin; Deegan, Brian; Cooke, John; Carew, Sheila; Hannigan, Ailish; Dunne, Colum; Lyons, Declan

2015-03-01

Elastic compression stockings (ECS) can be used as a non-pharmacological therapeutic option for older patients with orthostatic hypotension (OH). We aimed to investigate the practices and views of patients and physicians regarding the use of ECS for OH. Two surveys were designed. The first was sent to 90 patients known to have been prescribed ECS for OH. This questionnaire included items related to the frequency of use and issues related to non-compliance. The second was sent to 69 consultant physicians in geriatric medicine. This included items related to prescribing practices and perceived patient compliance. Sixty-seven patients responded (response rate, 74%) and of those 64% were female. Mean age (SD) was 75.1 years (10.5), range 45-91 years. Thirty-three per cent wore ECS daily, whereas 43% never used them. Over half (51%) of the patients reported difficulty in application and 31% reported discomfort. Those aged 75 or older were more likely to report difficulty in application (P=0.003). Forty-eight physicians responded (response rate, 70%). Eighty-nine per cent prescribe ECS for OH. There were significant differences between the frequency of use reported by patients and predicted by physicians (P<0.001), with physicians less likely to predict daily or non-use. Eighty-nine per cent of physicians predicted that difficulty in application was the main reason for non-compliance. Although prescribed frequently, the use of ECS in patients with OH is often limited by issues related to practicality. Physicians correctly predicted the main reasons for non-compliance although underestimated the scale of patient compliance with ECS. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Orthostatic Changes in Hemodynamics and Cardiovascular Biomarkers in Dysautonomic Patients

PubMed Central

Nilsson, David; Sutton, Richard; Tas, Widet; Burri, Philippe; Melander, Olle; Fedorowski, Artur

2015-01-01

Background Impaired autonomic control of postural homeostasis results in orthostatic intolerance. However, the role of neurohormones in orthostatic intolerance has not been explained. Methods Six-hundred-and-seventy-one patients (299 males; 55±22 years) with unexplained syncope underwent head-up tilt (HUT) with serial blood sampling. Systolic blood pressure (SBP) and heart rate (HR) supine, after 3min, and lowest BP/highest HR during HUT were recorded. Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal- endothelin-1 (CT-proET-1), and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were determined at supine and 3min of HUT. Multivariate-adjusted logistic regression model was applied to compare 1st (reference) with 4th quartile of 3 min and maximal ΔSBP/ΔHR (i.e. pronounced hypotension or tachycardia) vs. changes in neuroendocrine biomarkers, respectively. Results Higher resting CT-proET-1 predicted BP fall at 3min (Odds ratio (OR) per 1 SD: 1.62, 95%CI 1.18–2.22; p = 0.003), and max BP fall during HUT (1.82, 1.28–2.61; p = 0.001). Higher resting CT-proAVP predicted BP fall at 3min (1.33, 1.03–1.73; p = 0.03), which was also associated with increase in CT-proAVP (1.86, 1.38–2.51; p = 0.00005) and epinephrine (1.47, 1.12–1.92; p = 0.05) during HUT. Lower resting MR-proANP predicted tachycardia at 3min (0.37, 0.24–0.59; p = 0.00003), and max tachycardia during HUT (0.47, 0.29–0.77; p = 0.002). Further, tachycardia during HUT was associated with increase in epinephrine (1.60, 1.15–2.21; p = 0.005), and norepinephrine (1.87, 1.38–2.53; p = 0.005). Conclusions Resting CT-proET-1 and CT-proAVP are increased in orthostatic hypotension, while resting MR-proANP is decreased in postural tachycardia. Moreover, early BP fall during orthostasis evokes increase in CT-proAVP and epinephrine, while postural tachycardia is associated with increase in norepinephrine and epinephrine

The association between orthostatic hypotension and cognitive state among adults 65 years and older who underwent a comprehensive geriatric assessment

PubMed Central

Punchick, Boris; Freud, Tamar; Press, Yan

2016-01-01

Abstract The prevalence of cognitive impairment and orthostatic hypotension (OH) increases with age, but the results of studies that assessed possible associations between them are inconsistent. The aim of this study is to assess possible associations between cognitive impairment and OH in patients ≥65 years of age who underwent a comprehensive geriatric assessment. A retrospective analysis was conducted of the computerized medical records of the study population from 2005 to 2013. Data collected included blood pressure measurements that enabled the calculation of OH, results of the mini-mental state examination (MMSE), results of the Montreal cognitive assessment (MoCA) test, and cognitive diagnoses that were determined over the course of the assessment. The rate of OH in the study population of 571 adults was 32.1%. The mean MMSE score was 22.5 ± 5.2 among participants with OH and 21.6 ± 5.8 among those without OH (P = 0.09). The absence of a significant association between OH and MMSE remained after adjusting the MMSE score for age and education level. The mean MoCA score was 16.4 ± 5.0 among participants with OH and 16.4 ± 4.8 among those without (P = 0.33). The prevalence of OH was 39% among participants without cognitive impairment, 28.9% among those with mild cognitive impairment (MCI), and 30.6% among those with dementia (P = 0.13). There was no association between OH and cognitive impairment in adults who underwent a comprehensive geriatric assessment. PMID:27442658

Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia

NASA Technical Reports Server (NTRS)

Ketch, Terry; Biaggioni, Italo; Robertson, RoseMarie; Robertson, David

2002-01-01

BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.

Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease.

PubMed

Shibao, Cyndya A; Kaufmann, Horacio

2017-11-01

Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.

Prevalence and associative factors of orthostatic hypotension in older adults: Results from the Well-being of the Singapore Elderly (WiSE) study.

PubMed

Ong, Hui Lin; Abdin, Edimansyah; Seow, Esmond; Pang, Shirlene; Sagayadevan, Vathsala; Chang, Sherilyn; Vaingankar, Janhavi Ajit; Chong, Siow Ann; Subramaniam, Mythily

2017-09-01

Orthostatic hypotension (OH) is commonly reported among older adults and is associated with an increased risk of mortality. This study aimed to describe the prevalence and investigate the possible associations between OH with sociodemographic variables, chronic medical conditions, health service utilisation, dementia and cognitive status among older adults residing in Singapore. Data was collected from 2266 participants aged 60 years and older who participated in the Well-being of the Singapore Elderly (WiSE) study in 2013. Face-to-face interviews were conducted and data collected includes sociodemographic information, blood pressure measurements, medical history, health services utilisation, and cognitive status. The prevalence of OH among older adults in Singapore was 7.8%. OH was highest in participants aged 85 years and above (OR: 2.33; 1.26-4.30; p=0.007) compared to those aged 75-84 years (OR: 1.76; 1.08-2.85; p=0.023). Participants with hypertension were more likely to have OH (OR: 3.03; 1.56-5.88, p=0.001) than those without hypertension. Those with dementia were also more likely to have OH than those with normal cognitive status (p=0.007). Older age, hypertension, and dementia were independently associated with OH in the older adult population in Singapore. Interventions such as home safety assessment and preventive measures should be implemented to improve older adult's functional capacity and quality of life to prevent injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Orthostatic Hypotension (Postural Hypotension)

MedlinePlus

... is usually caused by something obvious, such as dehydration or lengthy bed rest, and is easily treated. ... lightheadedness may be fairly minor — triggered by mild dehydration, low blood sugar or overheating. Dizziness or lightheadedness ...

Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Engelke, K. A.; Doerr, D. F.

1999-01-01

Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

NASA Technical Reports Server (NTRS)

Lee, Stuart M. C.; Feiveson, Alan H.; Stenger, Michael B.; Stein, Sydney P.; Platts, Steven H.

2011-01-01

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the

Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance

NASA Technical Reports Server (NTRS)

Schroeder, Christoph; Tank, Jens; Boschmann, Michael; Diedrich, Andre; Sharma, Arya M.; Biaggioni, Italo; Luft, Friedrich C.; Jordan, Jens; Robertson, D. (Principal Investigator)

2002-01-01

BACKGROUND: Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. METHODS AND RESULTS: We studied the effect of the selective NET blocker reboxetine and placebo in a randomized, double-blind, crossover fashion on cardiovascular responses to cold pressor testing, handgrip testing, and a graded head-up tilt test (HUT) in 18 healthy subjects. In a subset, we determined isoproterenol and phenylephrine sensitivities. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. In the supine position, heart rate was 65+/-2 bpm with placebo and 71+/-3 bpm with reboxetine. At 75 degrees HUT, heart rate was 84+/-3 and 119+/-4 bpm with placebo and with reboxetine (P<0.0001). Mean arterial pressure was 85+/-2 with placebo and 91+/-2 mm Hg with reboxetine while supine (P<0.01) and 88+/-2 mm Hg and 90+/-3 mm Hg at 75 degrees HUT. Blood pressure responses to cold pressor and handgrip testing were attenuated with reboxetine. Reboxetine increased the sensitivity to the chronotropic effect of isoproterenol and the pressor effect of phenylephrine. Vasovagal reactions occurred in 9 subjects on placebo and in 1 subject on reboxetine. CONCLUSIONS: Selective NET blockade creates a phenotype that resembles idiopathic orthostatic intolerance. This observation supports the hypothesis that disordered norepinephrine uptake mechanisms can contribute to human cardiovascular disease. Our study also suggests that NET inhibition might be useful in preventing vasovagal reactions.

Pathophysiology and management of spontaneous intracranial hypotension--a review.

PubMed

Syed, Nadir Ali; Mirza, Farhan Arshad; Pabaney, Aqueel Hussain; Rameez-ul-Hassan

2012-01-01

Spontaneous Intracranial Hypotension is a syndrome involving reduced intracranial pressure secondary to a dural tear which occurs mostly due to connective tissue disorders such as Marfans Syndrome, and Ehler Danlos Syndrome. Patients with dural ectasias leading to CSF leakage into the subdural or epidural space classically present with orthostatic headaches and cranial nerve deficits mostly seen in cranial nerves V-VIII. Diagnosis of SIH is confirmed with the aid of neuroimaging modalities of which Cranial MR imaging is most widely used. SIH can be treated conservatively or with epidural blood patches which are now widely being used to repair dural tears, and their effectiveness is being recognized. Recently epidural injection of fibrin glue has also been used which has been found to be effective in certain patients.

Orthostatic Hypotension

MedlinePlus

... the body), resulting from the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or ... the body), resulting from the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or ...

Cost-effectiveness of droxidopa in patients with neurogenic orthostatic hypotension: post-hoc economic analysis of Phase 3 clinical trial data.

PubMed

François, Clément; Hauser, Robert A; Aballéa, Samuel; Dorey, Julie; Kharitonova, Elizaveta; Hewitt, L Arthur

2016-01-01

Falls are associated with neurogenic orthostatic hypotension (nOH) and are an economic burden on the US healthcare system. Droxidopa is approved by the US FDA to treat symptomatic nOH. This study estimates the cost-effectiveness of droxidopa vs standard of care from a US payer perspective. A Markov model was used to predict numbers of falls and treatment responses using data from a randomized, double-blind trial of patients with Parkinson's disease and nOH who received optimized droxidopa therapy or placebo for 8 weeks. The severity of falls, utility values, and injury-related costs were derived from published studies. Model outcomes included number of falls, number of quality-adjusted life-years (QALYs), and direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated. Outcomes were extrapolated over 12 months. Patients receiving droxidopa had fewer falls compared with those receiving standard of care and gained 0.33 QALYs/patient. Estimated droxidopa costs were $30,112, with estimated cost savings resulting from fall avoidance of $14,574 over 12 months. Droxidopa was cost-effective vs standard of care, with ICERs of $47,001/QALY gained, $24,866 per avoided fall with moderate/major injury, and $1559 per avoided fall with no/minor injury. The main drivers were fall probabilities and fear of fall-related inputs. A limitation of the current study is the reliance on falls data from a randomized controlled trial where the placebo group served as the proxy for standard of care. Data from a larger patient population, reflecting 'real-life' patient use and/or comparison with other agents used to treat nOH, would have been a useful complement, but these data were not available. Using Markov modeling, droxidopa appears to be a cost-effective option compared with standard of care in US clinical practice for the treatment of nOH.

Orthostatic tremor: a cerebellar pathology?

PubMed Central

Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

2016-01-01

Abstract See Muthuraman et al. (doi:10.1093/aww164) for a scientific commentary on this article. Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects. PMID:27329770

[Headhache secondary to intracranial hypotension in a Lumbar Spinal Stenosis Surgery].

PubMed

Hidalgo-Mendía, Begoña; Angulo-Tabernero, Marina; Jaroid-Audes, Ricardo; Untoria-Agustín, Carmen; Rivero-Zelada, David

2016-01-01

Intracraneal hypotension headache is a well known syndrome in neurosurgery practice. In most cases cerebrospinal fluid leaks are caused by medical interventions, such as lumbar puncture, peridural anesthesia and surgical interventions on the spine. Clinical symptoms tipically show orthostatic headache that resolves in supine position, and other symptoms like neck tightness, vertigo and diplopia. RMI diagnostic confirms paquimeningeal enhancement and subdural hygromas. Conservative treatment usually includes bed resting, hydratation and administration of caffeine or glucocorticoids, resolving spontaneously in one to four months. The importance of the diagnosis lies in the differential diagnosis with other causes of headache, as symptomatic limiting factor in the rehabilitation of the patient and the same favorable prognosis.

Orthostatic tremor: a cerebellar pathology?

PubMed

Gallea, Cécile; Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

2016-08-01

SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Cardiovascular resistance to orthostatic stress in athletes after aerobic exercise].

PubMed

Mel'nikov, A A; Popov, S G; Vikulov, A D

2014-01-01

In the paper cardiovascular resistance to orthostatic stress in the athletes in the two-hour recovery period after prolonged aerobic exercise was investigated. The reaction of the cardiac (stroke volume and cardiac output) and peripheral blood volumes in the lower and upper limbs, abdominal and neck regions in response to the tilt-test before and during two hours after exercise (30 min, heart rate = 156 +/- 8 beats/min) was determined by impedance method: It is found that: (1) at baseline distribution of blood flow in favor of the neck-region in response to the tilt-test, in spite of the decrease in cardiac output, was more efficient in athletes, that was due to a large decrease in blood flow to the lower extremities, and increased blood flow in the neck region; (2) after exercise it was established symptoms of potential orthostatic intolerance: postural hypotension and tachycardia, reduced peripheral pulse blood volume, expressed in a standing position, and reduced effectiveness of the distribution of blood flow in the direction of the neck region; (3) the abilityto effectively distribute blood flow in favor of the neck region in athletes after exercise remained elevated, which was due to a large decrease in blood flow in the abdominal region at the beginning, and in the lower limbs at the end of the recovery period.

Individual Differences in the Temporal Profile of Cardiovascular Responses to Head Down Tilt and Orthostatic Stress with and Without Fluid Loading

NASA Technical Reports Server (NTRS)

Cowings, Patricia; Toscano, William; Kanis, Dionisios; Gebreyesus, Fiyore

2013-01-01

Susceptibility of healthy astronauts to orthostatic hypotension and presyncope is exacerbated upon return from spaceflight. Hypo-volemia is suspected to play an important role in cardiovascular deconditioning following exposure to spaceflight, which may lead to increased peripheral resistance, attenuated arterial baroreflex, and changes in cardiac function. The effect of altered gravity during space flight and planetary transition on human cardiovascular function is of critical importance to maintenance of astronaut health and safety. A promising countermeasure for post-flight orthostatic intolerance is fluid loading used to restore loss fluid volume by giving crew salt tablets and water prior to re-entry. Eight men and eight women will be tested during two, 6-hour exposures to 6o HDT: 1) fluid loading, 2) no fluid loading. Before and immediately after each HDT, subjects will perform a stand test to assess their orthostatic tolerance. Physiological measures (e.g., ECG, blood pressure, peripheral blood volume) will be continuously monitored while echocardiography measures are recorded at 30-minute intervals during HDT and stand tests. Preliminary results (N=4) clearly show individual differences in responses to this countermeasure and the time course of physiological changes induced by HDT.

Greater change of orthostatic blood pressure is related to silent cerebral infarct and cardiac overload in hypertensive subjects.

PubMed

Eguchi, Kazuo; Kario, Kazuomi; Hoshide, Satoshi; Hoshide, Yoko; Ishikawa, Joji; Morinari, Masato; Hashimoto, Toru; Shimada, Kazuyuki

2004-04-01

Greater change of postural blood pressure (BP) is often seen in elderly hypertensives and is recognized as a risk factor for cognitive decline and poorer cerebrovascular outcome, but its clinical significance still remains to be clarified. We performed a head-up tilting test, ambulatory BP monitoring, and brain MRI in 59 hypertensives and 27 normotensive subjects. We measured plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels at rest to assess cardiac burden. The 59 hypertensive patients were classified into 3 groups: an orthostatic hypertension (OHT) group with orthostatic increase in systolic BP (SBP) > or = 10 mmHg (n=16); an orthostatic hypotension (OHYPO) group with orthostatic SBP decrease < or = -10 mmHg (n=18); and an orthostatic normotension (ONT) group with neither of these two patterns (n=25). A group of 27 normotensive subjects (NT) was also included as a control. Plasma BNP (72 +/- 92 vs. 29 +/- 24 pg/ml, p < 0.05) and BNP/ANP ratio (4.6 +/- 3.3 vs. 2.4 +/- 1.5, p < 0.05) were significantly higher in the OHYPO than in the NT group. The BNP/ANP ratio was also higher in the OHT than in the NT group (5.1 +/- 3.9 vs. 2.4 +/- 1.5, p < 0.01). The number of silent cerebral infarct (SCI), prevalence of SCI and number of multiple SCIs was the highest in the OHT group, followed in order by the OHYPO, ONT and NT groups. Blood pressure and left ventricular mass index were not significantly different among the 3 hypertensive groups. In conclusion, hypertensive patients with greater change of postural BP (OHT and OHYPO) were shown to have increased risk of advanced silent brain lesions and greater cardiac burden.

Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options

PubMed Central

Wagoner, Ashley L.; Shaltout, Hossam A.; Fortunato, John E.

2015-01-01

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10–18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

2002-01-01

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures.

PubMed

Convertino, Victor A

2002-12-01

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Plasma biomarkers of decreased vesicular storage distinguish Parkinson disease with orthostatic hypotension from the parkinsonian form of multiple system atrophy.

PubMed

Goldstein, David S; Kopin, Irwin J; Sharabi, Yehonatan; Holmes, Courtney

2015-02-01

Parkinson disease with orthostatic hypotension (PD + OH) and the parkinsonian form of multiple system atrophy (MSA-P) can be difficult to distinguish clinically. Recent studies indicate that PD entails a vesicular storage defect in catecholaminergic neurons. Although cardiac sympathetic neuroimaging by (18)F-dopamine positron emission tomography can identify decreased vesicular storage, this testing is not generally available. We assessed whether plasma biomarkers of a vesicular storage defect can separate PD + OH from MSA-P. We conceptualized that after F-dopamine injection, augmented production of F-dihydroxyphenylacetic acid (F-DOPAC) indicates decreased vesicular storage, and we therefore predicted that arterial plasma F-DOPAC would be elevated in PD + OH but not in MSA-P. We measured arterial plasma F-DOPAC after (18)F-dopamine administration (infused i.v. over 3 min) in patients with PD + OH (N = 12) or MSA-P (N = 21) and in healthy control subjects (N = 26). Peak F-DOPAC:dihydroxyphenylglycol (DHPG) was also calculated to adjust for effects of denervation on F-DOPAC production. Plasma F-DOPAC accumulated rapidly after initiation of (18)F-dopamine infusion. Peak F-DOPAC (5-10 min) in PD + OH averaged three times that in MSA-P (P < 0.0001). Among MSA-P patients, none had peak F-DOPAC > 300 nCi-kg/cc-mCi, in contrast with 7 of 12 PD + OH patients (χ(2) = 16.6, P < 0.0001). DHPG was lower in PD + OH (3.83 ± 0.36 nmol/L) than in MSA-P (5.20 ± 0.29 nmol/L, P = 0.007). All MSA-P patients had peak F-DOPAC:DHPG < 60, in contrast with 9 of 12 PD + OH patients (χ(2) = 17.5, P < 0.0001). Adjustment of peak F-DOPAC for DHPG increased test sensitivity from 58 to 81% at similar high specificity. After F-dopamine injection, plasma F-DOPAC and F-DOPAC:DHPG distinguish PD + OH from MSA-P.

The long-term outcome of orthostatic tremor.

PubMed

Ganos, Christos; Maugest, Lucie; Apartis, Emmanuelle; Gasca-Salas, Carmen; Cáceres-Redondo, María T; Erro, Roberto; Navalpotro-Gómez, Irene; Batla, Amit; Antelmi, Elena; Degos, Bertrand; Roze, Emmanuel; Welter, Marie-Laure; Mestre, Tiago; Palomar, Francisco J; Isayama, Reina; Chen, Robert; Cordivari, Carla; Mir, Pablo; Lang, Anthony E; Fox, Susan H; Bhatia, Kailash P; Vidailhet, Marie

2016-02-01

Orthostatic tremor is a rare condition characterised by high-frequency tremor that appears on standing. Although the essential clinical features of orthostatic tremor are well established, little is known about the natural progression of the disorder. We report the long-term outcome based on the largest multicentre cohort of patients with orthostatic tremor. Clinical information of 68 patients with clinical and electrophysiological diagnosis of orthostatic tremor and a minimum follow-up of 5 years is presented. There was a clear female preponderance (76.5%) with a mean age of onset at 54 years. Median follow-up was 6 years (range 5-25). On diagnosis, 86.8% of patients presented with isolated orthostatic tremor and 13.2% had additional neurological features. At follow-up, seven patients who initially had isolated orthostatic tremor later developed further neurological signs. A total 79.4% of patients reported worsening of orthostatic tremor symptoms. These patients had significantly longer symptom duration than those without reported worsening (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in orthostatic tremor frequency over time. Structural imaging was largely unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases. Pharmacological treatments were disappointing. Two patients were treated surgically and showed improvement. Orthostatic tremor is a progressive disorder with increased disability although tremor frequency is unchanged over time. In most cases, orthostatic tremor represents an isolated syndrome. Drug treatments are unsatisfactory but surgery may hold promise. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Orthostatic intolerance: potential pathophysiology and therapy.

PubMed

Lu, Chih-Cherng; Tseng, Ching-Jiunn; Tang, Hung-Shang; Tung, Che-Se

2004-09-30

Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, syncope. Syncope is the most hazardous symptom of orthostatic intolerance, presumably occurring because of impaired cerebral perfusion and in part to compensatory autonomic mechanisms. The etiology of this syndrome is still unclear but is heterogeneous. Orthostatic intolerance used to be characterized by an overall enhancement of noradrenergic tone at rest in some patients and by a patchy dysautonomia of postganglionic sympathetic fibers with a compensatory cardiac sympathetic activation in others. However, recent advances in molecular genetics are improving our understanding of orthostatic intolerance, such as several genetic diseases (such as Ehler-Danlos syndrome and norepinephrine transporter deficiency) presenting with symptoms typical of orthostatic intolerance. Future work will include investigation of genetic functional mutations underlying interindividual differences in autonomic cardiovascular control, body fluid regulation, and vascular regulation in orthostatic intolerance patients. The goal of this review article is to describe recent advances in understanding the pathophysiological mechanisms of orthostatic intolerance and their clinical significance.

Noninvasive beat-to-beat finger arterial pressure monitoring during orthostasis: a comprehensive review of normal and abnormal responses at different ages.

PubMed

van Wijnen, V K; Finucane, C; Harms, M P M; Nolan, H; Freeman, R L; Westerhof, B E; Kenny, R A; Ter Maaten, J C; Wieling, W

2017-12-01

Over the past 30 years, noninvasive beat-to-beat blood pressure (BP) monitoring has provided great insight into cardiovascular autonomic regulation during standing. Although traditional sphygmomanometric measurement of BP may be sufficient for detection of sustained orthostatic hypotension, it fails to capture the complexity of the underlying dynamic BP and heart rate responses. With the emerging use of noninvasive beat-to-beat BP monitoring for the assessment of orthostatic BP control in clinical and population studies, various definitions for abnormal orthostatic BP patterns have been used. Here, age-related changes in cardiovascular control in healthy subjects will be reviewed to define the spectrum of the most important abnormal orthostatic BP patterns within the first 180 s of standing. Abnormal orthostatic BP responses can be defined as initial orthostatic hypotension (a transient systolic BP fall of >40 mmHg within 15 s of standing), delayed BP recovery (an inability of systolic BP to recover to a value of >20 mmHg below baseline at 30 s after standing) and sustained orthostatic hypotension (a sustained decline in systolic BP of ≥20 mmHg occurring 60-180 s after standing). In the evaluation of patients with light-headedness, pre(syncope), (unexplained) falls or suspected autonomic dysfunction, it is essential to distinguish between normal cardiovascular autonomic regulation and these abnormal orthostatic BP responses. The prevalence, clinical relevance and underlying pathophysiological mechanisms of these patterns differ significantly across the lifespan. Initial orthostatic hypotension is important for identifying causes of syncope in younger adults, whereas delayed BP recovery and sustained orthostatic hypotension are essential for evaluating the risk of falls in older adults. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Improvements in Orthostatic Instability with Stand Locomotor Training in Individuals with Spinal Cord Injury

PubMed Central

Harkema, Susan J.; Ferreira, Christie K.; van den Brand, Rubia J.

2008-01-01

Abstract Prospective assessment of cardiovascular control in individuals with spinal cord injury (SCI) in response to active stand training. Cardiovascular parameters were measured at rest and in response to orthostatic challenge before and after training in individuals with clinically complete SCI. The goal of this study was to evaluate the effect of active stand training on arterial blood pressure and heart rate and changes in response to orthostatic stress in individuals with SCI. Measurements were obtained in individuals with SCI (n = 8) prior to and after 40 and 80 sessions of the standing component of a locomotor training intervention (stand LT). During standing, all participants wore a harness and were suspended by an overhead, pneumatic body weight support (BWS) system over a treadmill. Trainers provided manual facilitation as necessary at the trunk and legs. All individuals were able to bear more weight on their legs after the stand LT training. Resting arterial blood pressure significantly increased in individuals with cervical SCI after 80 training sessions. At the end of the training period, resting systolic blood pressure (BP) in individuals with cervical SCI in a seated position, increased by 24% (from 84 ± 5 to 104 ± 7 mmHg). Furthermore, orthostatic hypotension present in response to standing prior to training (decrease in systolic BP of 24 ± 14 mmHg) was not evident (decrease in systolic BP of 0 ± 11 mmHg) after 80 sessions of stand LT. Hemodynamic parameters of individuals with thoracic SCI were relatively stable prior to training and not significantly different after 80 sessions of stand LT. Improvements in resting arterial blood pressure and responses to orthostatic stress in individuals with clinically complete cervical SCI occurred following intensive stand LT training. These results may be attributed to repetitive neuromuscular activation of the legs from loading and/or conditioning of cardiovascular responses from

ORTHO-LBNP: A new apparatus for assessing autocontrol mechanisms of the heart-vessel system in pilots undergoing training in conditions of ischemic hypoxia and orthostatic stress

NASA Astrophysics Data System (ADS)

Truszczynski, Olaf; Skibniewski, Franciszek; Dziuda, Lukasz; Gacek, Adam; Krej, Mariusz; Sobotnicki, Aleksander; Rajchel, Jan; Bylinka, Marek; Burek, Michal

The authors present a new system for examining the behaviour of the human body and cerebral circulation in conditions of ischemic hypoxia and orthostatic stress that can cause orthostatic hypotension. Ischemic hypoxia affects mainly pilots of highly manoeuvrable aircraft, where long-lasting G forces not seldom reach 6-8 +Gz and can exceed the gravitational acceleration by ten times or more. Additionally, pilots are subjected to orthostatic hypotension in which abnormally low blood pressure is caused by pressure adjustment disorder and decreased stroke volume when changing body position rapidly. For several decades, these effects have been deeply investigated using human centrifuges or lower body negative pressure (LBNP) chambers. The latter method involves significantly less financial resources to carry out experiments and training, whereas the effects exerted on pilots, and the results of the training can be comparable. A group of researchers from the Military Institute of Aviation Medicine, Warszawa, Poland, and the Institute of Medical Technology and Equipment ITAM, Zabrze, Poland, are developing the innovative ORTHO-LBNP device based on the cradle principle and the LBNP method. The system will be implemented in a modern programme for training cadets of the Polish Air Force Academy, Dęblin, Poland. Together with other equipment such as a high-G centrifuge, pressure chambers, flight and spatial disorientation simulators as well as gymnastic training equipment for pilots (GTEP), the ORTHO-LBNP apparatus will be an element of the selection system of candidates for aviation. It is expected that the experimental studies will result in developing new indicators providing an objective assessment, whether examined persons possess the traits necessary for performing tasks related to the job of a pilot. It is highly probable that those indicators can be incorporated into routine checks for pilots, which in turn, can lead to improving the safety of flight operations and

Subdural hematoma caused by intracranial hypotension after syringosubarachnoid shunting--case report.

PubMed

Yamazaki, Tomosato; Yanaka, Kiyoyuki; Uemura, Kazuya; Tsukada, Atsuro

2004-09-01

A 32-year-old man developed an extremely rare subdural hematoma after syringosubarachnoid shunting for syringomyelia. He presented with a 4-year history of neck pain and spastic paraparesis resulting from T-7 and T-8 vertebral body fracture suffered in a traffic accident at age 22 years. Magnetic resonance imaging revealed syringomyelia between the craniocervical junction and the T-10 level. The symptoms were slowly progressive, and a syringosubarachnoid shunting was performed. His spasticity improved after surgery, but he developed orthostatic headache 7 days after surgery. Magnetic resonance imaging of the brain demonstrated a thin subdural hematoma over the right cerebral convexity. The subdural hematoma resolved spontaneously within a week with conservative treatment. Vigorous cerebrospinal fluid outflow observed during surgery presumably lowered the pressure in the syrinx cavity, leading to significant but transient intracranial hypotension and consequently the formation of subdural hematoma.

Compression Stockings May Ameliorate Orthostatic Intolerance in Astronauts After Short-Duration Space Flight

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Lee, Stuart M. C.; Westby, Christian M.; Ribeiro, L. Christine; Stenger, Michael B.

2011-01-01

Orthostatic intolerance following spaceflight has been observed since the early days of manned spaceflight, and no countermeasure has been 100% effective. During re-entry NASA astronauts currently wear an inflatable anti-gravity suit (AGS) which compresses the legs and abdomen, but this device is uncomfortable and loses effectiveness upon egress from the Space Shuttle. We previously reported that foot-to-thigh, gradient compression stockings were comfortable and effective during standing after Shuttle missions. More recently we showed in a ground-based model of spaceflight that the addition of splanchnic compression to the foot-to-thigh compression stockings, creating foot-to-breast high compression, improved orthostatic tolerance in hypovolemic subjects to a level similar to the AGS. Purpose: To evaluate a new three-piece, foot-to-breast high gradient compression garment as a countermeasure to post-spaceflight orthostatic intolerance. Methods: Fourteen astronauts completed this experiment (7 control, 7 treatment) following Space Shuttle missions lasting 12-16 days. Treatment subjects were custom-fitted for a three-piece, foot-to-breast high compression garment consisting of shorts and foot-to-thigh stockings. The garments were constructed to provide 55 mmHg compression at the ankle and decreased gradually to 15 mmHg over the abdomen. Orthostatic testing occurred 30 days before flight (without garments) and 2 hours after flight (with garments for treatment group only) on landing day. Blood pressure (BP) and heart rate (HR) were acquired for 2 minutes while the subject lay prone and then for 3.5 minutes after the subject stood. Data are reported as mean +/- SE. Results: The compression garment successfully prevented the tachycardia and hypotension typically seen post-spaceflight. On landing day, treatment subjects had a smaller change in HR (11+/-1 vs. 21+/-4 beats/min, p< or =0.05) and no decrease in systolic BP (2+/-4 vs. -9+/-2 mmHg, p< or =0.05). Garments also

Athletes, astronauts and orthostatic tolerance.

PubMed

Harrison, M H

1986-01-01

Specific alterations in autonomic functions induced by endurance training may lead to a reduced ability to withstand orthostatic stress. This possibility has caused some authorities to suggest that, because of potentially greater pooling of blood in the lower extremities during gravitational loading, endurance-trained athletes may make poor astronauts. Although results from spaceflight studies have provided little evidence to support this suggestion, data from water-immersion studies indicate that endurance-trained athletes do become more orthostatically intolerant following a few hours of simulated weightlessness. Unfortunately, other evidence supporting the hypothesis that endurance training reduces orthostatic tolerance has not received adequate publication in the open scientific literature. On the other hand, a number of studies which have been openly reported clearly refute this hypothesis. Nevertheless, the established physiological differences between endurance athletes and non-athletes are themselves sufficient to suggest that the hypothesis could be tenable. Consequently, it has to be concluded that the presently available information is both qualitatively and quantitatively inadequate to permit any definite statement regarding a possible relationship between aerobic power (VO2max) and orthostatic tolerance.

What Is Hypotension?

MedlinePlus

... Hypotension Hypotension Also known as What Is Hypotension (HI-po-TEN-shun) is abnormally low blood pressure. ... this type of low blood pressure. Dehydration (de-hi-DRA-shun) is the most common cause of ...

Mechanisms of orthostatic intolerance during heat stress

PubMed Central

Schlader, Zachary J.; Wilson, Thad E.; Crandall, Craig G.

2017-01-01

Heat stress profoundly and unanimously reduces orthostatic tolerance. This review aims to provide an overview of the numerous and multifactorial mechanisms by which this occurs in humans. Potential causal factors include changes in arterial and venous vascular resistance and blood distribution, and the modulation of cardiac output, all of which contribute to the inability to maintain cerebral perfusion during heat and orthostatic stress. A number of countermeasures have been established to improve orthostatic tolerance during heat stress, which alleviate heat stress induced central hypovolemia (e.g., volume expansion) and/or increase peripheral vascular resistance (e.g., skin cooling). Unfortunately, these countermeasures can often be cumbersome to use with populations prone to syncopal episodes. Identifying the mechanisms of inter-individual differences in orthostatic intolerance during heat stress has proven elusive, but could provide greater insights into the development of novel and personalized countermeasures for maintaining or improving orthostatic tolerance during heat stress. This development will be especially impactful in occuational settings and clinical situations that present with orthostatic intolerance and/or central hypovolemia. Such investigations should be considered of vital importance given the impending increased incidence of heat events, and associated cardiovascular challenges that are predicted to occur with the ensuing changes in climate. PMID:26723547

A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction: Preclinical correlate to a clinical test.

PubMed

Bhatt, Siddhartha; Foote, Stephen; Smith, Andrew; Butler, Paul; Steidl-Nichols, Jill

2015-01-01

Drug induced orthostatic hypotension (OH) is an important clinical concern and can be an unexpected hurdle during drug development. OH is defined as an abnormal decrease in blood pressure (BP) triggered by a rapid postural change. The sympathetic nervous system is critical for controlling normal cardiovascular function and compensatory responses to changes in posture. Thus, OH can also serve as a surrogate indicator of sympathetic dysfunction. However, preclinical conscious models for investigating risk of OH and/or sympathetic dysfunction are lacking. Herein, we describe a conscious nonhuman primate (NHP) model which mimics the widely used clinical tilt table test for OH. Male, Cynomolgus NHPs (n = 7-8) implanted with radio-telemetry transmitters were placed in modified tilt chairs in a supine position. Subsequently, a 90° head up tilt was performed for 3 min followed by return to the supine position. BP and heart rate were continuously monitored. Test compounds were administered either intravenously or via oral gavage in a crossover design, with blood samples collected at the end of the each tilt to assess total drug concentrations. Tilt responses were assessed following treatment with positive control compounds that cause sympathetic dysfunction; hexamethonium (ganglionic blocker) and prazosin (alpha-1 adrenergic receptor antagonist). Both compounds induced marked OH as evidenced by robust and sustained BP reduction in response to a head up tilt (decrease of 25-35 mmHg for hexamethonium, decrease of 21-44 mmHg for prazosin). OH incidence rates increased in a dose-dependent manner. OH incidences following treatment with minoxidil (vasodilator) were markedly lower to those observed with hexamethonium and prazosin indicating the role of sympathetic dysfunction in causing OH. These data demonstrate that the NHP tilt test is a valuable model for investigating OH risk. This model fills an important preclinical gap for assessing such a safety concern and can be

Low blood pressure

MedlinePlus

Hypotension; Blood pressure - low; Postprandial hypotension; Orthostatic hypotension; Neurally mediated hypotension; NMH ... Blood pressure varies from one person to another. A drop as little as 20 mmHg, can cause ...

Endurance exercise training in orthostatic intolerance: a randomized, controlled trial.

PubMed

Winker, Robert; Barth, Alfred; Bidmon, Daniela; Ponocny, Ivo; Weber, Michael; Mayr, Otmar; Robertson, David; Diedrich, André; Maier, Richard; Pilger, Alex; Haber, Paul; Rüdiger, Hugo W

2005-03-01

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.

Dose-response related efficacy in orthostatic hypotension of a fixed combination of D-camphor and an extract from fresh crataegus berries and the contribution of the single components.

PubMed

Belz, Gustav Georg; Loew, Dieter

2003-01-01

Independent, double-blinded, randomized, placebo-controlled studies using sublingual/oral administration of D-camphor, an extract from fresh crataegus berries, and a combination of the two (CCC) yielded the following results: Both the D-camphor and the extract from fresh crataegus berries, the components of CCC, contribute to the pressoric effects of the combination. The underlying hemodynamic mechanisms can be attributed to an increase in total peripheral resistance induced by an increased tone of the arterioles with both components and the effect of crataegus is intensified by an additional direct positive action on cardiac performance. Conceivably, the D-camphor component is the main factor in inducing the rapid initial effect, whereas the extract from fresh crataegus berries adds a long-lasting effect. For CCC, a dose-dependent increase in supine blood pressure and prevention of orthostatic fall in blood pressure following tilt table-induced orthostasis in patients with orthostatic dysregulation was demonstrated as well. The effect revealed a very rapid onset of action within 1 min following administration, confirming the traditional use in emergency situations such as orthostatic (pre)syncope. Thus, these studies show that CCC, depending on the pressoric activity of its two mono-components, exerts a significant effect that counteracts an orthostatic fall in blood pressure and thereby provides a rationale for its application that reemphasizes the decades-long usefulness of this phyto-combination.

Orthostatic Intolerance in Older Persons: Etiology and Countermeasures

PubMed Central

Goswami, Nandu; Blaber, Andrew P.; Hinghofer-Szalkay, Helmut; Montani, Jean-Pierre

2017-01-01

Orthostatic challenge produced by upright posture may lead to syncope if the cardiovascular system is unable to maintain adequate brain perfusion. This review outlines orthostatic intolerance related to the aging process, long-term bedrest confinement, drugs, and disease. Aging-associated illness or injury due to falls often leads to hospitalization. Older patients spend up to 83% of hospital admission lying in bed and thus the consequences of bedrest confinement such as physiological deconditioning, functional decline, and orthostatic intolerance represent a central challenge in the care of the vulnerable older population. This review examines current scientific knowledge regarding orthostatic intolerance and how it comes about and provides a framework for understanding of (patho-) physiological concepts of cardiovascular (in-) stability in ambulatory and bedrest confined senior citizens as well as in individuals with disease conditions [e.g., orthostatic intolerance in patients with diabetes mellitus, multiple sclerosis, Parkinson's, spinal cord injury (SCI)] or those on multiple medications (polypharmacy). Understanding these aspects, along with cardio-postural interactions, is particularly important as blood pressure destabilization leading to orthostatic intolerance affects 3–4% of the general population, and in 4 out of 10 cases the exact cause remains elusive. Reviewed also are countermeasures to orthostatic intolerance such as exercise, water drinking, mental arithmetic, cognitive training, and respiration training in SCI patients. We speculate that optimally applied countermeasures such as mental challenge maintain sympathetic activity, and improve venous return, stroke volume, and consequently, blood pressure during upright standing. Finally, this paper emphasizes the importance of an active life style in old age and why early re-mobilization following bedrest confinement or bedrest is crucial in preventing orthostatic intolerance, falls and falls

Standing orthostatic blood pressure measurements cannot be replaced by sitting measurements.

PubMed

Breeuwsma, Anna C; Hartog, Laura C; Kamper, Adriaan M; Groenier, Klaas H; Bilo, Henk Jg; Kleefstra, Nanne; Van Hateren, Kornelis Jj

2017-08-01

As many elderly patients are not able to stand for several minutes, sitting orthostatic blood pressure (BP) measurements are sometimes used as an alternative. We aimed to investigate the difference in BP response and orthostatic hypotension (OH) prevalence between the standard postural change to the sitting and the standing position in a cross-sectional observational study. BP was measured with a continuous BP measurement device during two postural changes, from supine to the sitting and from supine to the standing position. Linear mixed models were used to investigate the differences in changes (Δ) of systolic BP (SBP) and diastolic BP (DBP) between the two postural changes. The prevalence and the positive and negative proportions of agreement of OH were calculated of the two postural changes. One hundred and four patients with a mean age of 69 years were included. ΔSBP was significantly larger in the standing position compared with the sitting between 0 and 44 s. ΔDBP was significantly larger in the sitting position compared with the standing 75-224 s after postural change. The prevalence of OH was 66.3% (95% confidence interval (CI) 57.2, 75.4) in the standing position and 67.3% (95% CI 58.3, 76.3) in the sitting position. The positive proportion of agreement was 74.8% and the negative proportion of agreement was 49.3%. A clear difference was seen in BP response between the two postural changes. Although no significant difference in prevalence of OH was observed, the positive and negative proportion of agreement of the prevalence of OH were poor to moderate, which indicates a different outcome between both postural changes.

Autonomic control of heart rate during orthostasis and the importance of orthostatic-tachycardia in the snake Python molurus.

PubMed

Armelin, Vinicius Araújo; da Silva Braga, Victor Hugo; Abe, Augusto Shinya; Rantin, Francisco Tadeu; Florindo, Luiz Henrique

2014-10-01

Orthostasis dramatically influences the hemodynamics of terrestrial vertebrates, especially large and elongated animals such as snakes. When these animals assume a vertical orientation, gravity tends to reduce venous return, cardiac filling, cardiac output and blood pressure to the anterior regions of the body. The hypotension triggers physiological responses, which generally include vasomotor adjustments and tachycardia to normalize blood pressure. While some studies have focused on understanding the regulation of these vasomotor adjustments in ectothermic vertebrates, little is known about regulation and the importance of heart rate in these animals during orthostasis. We acquired heart rate and carotid pulse pressure (P PC) in pythons in their horizontal position, and during 30 and 60° inclinations while the animals were either untreated (control) or upon muscarinic cholinoceptor blockade and a double autonomic blockade. Double autonomic blockade completely eradicated the orthostatic-tachycardia, and without this adjustment, the P PC reduction caused by the tilts became higher than that which was observed in untreated animals. On the other hand, post-inclinatory vasomotor adjustments appeared to be of negligible importance in counterbalancing the hemodynamic effects of gravity. Finally, calculations of cardiac autonomic tones at each position revealed that the orthostatic-tachycardia is almost completely elicited by a withdrawal of vagal drive.

Orthostatic dizziness in Parkinson's disease is attributed to cerebral hypoperfusion: A transcranial doppler study.

PubMed

Park, Jinse; Kim, Hee-Tae; Park, Kang Min; Ha, Sam Yeol; Kim, Sung Eun; Shin, Kyong Jin; Kim, Si Eun; Jang, Wooyoung; Kim, Ji Sun; Youn, Jinyoung; Oh, Engsoek; Park, Suyeon

2017-07-08

Orthostatic hypotension (OH) is controversially regarded as the cause of orthostatic dizziness in Parkinson's disease (PD). We sought to evaluate whether cerebral autoregulation is an alternative cause for orthostatic dizziness in PD patients, using transcranial Doppler monitoring during head-up tilting. Forty-five PD patients with dizziness, 13 PD patients without dizziness, and 10 age-matched healthy controls were enrolled. Participants were divided into the following four groups: patients with dizziness and OH (group 1, n = 22), patients with dizziness but no OH (n = 23, group 2), patients without dizziness (n = 11, group 3), and age-matched healthy controls (n = 10, group 4). All participants underwent transcranial Doppler and blood pressure monitoring for 10 minutes during the head-up tilt test. Changes in the cerebral blood flow velocity (CBFV) in the middle cerebral artery and the mean blood pressure (mBP) within 3 minutes after head-up tilting were compared between groups. Group 1 showed a significantly higher change in mBP (-16.3 ± 10.8 mmHg) than groups 2 (-2.6 ± 4.9), 3 (-2.2 ± 3.6), or 4 (1.8 ± 6.0) (p < 0.001). However, groups 3 (4.6 ± 3.0 cm/s) and 4 (-4.2 ± 2.5) showed a significantly smaller change in CBFV than groups 1 (-9.0 ± 4.2) and 2 (-8.1 ± 5.1) (p < 0.01). Our results suggest that cerebral hypoperfusion contributes to dizziness in PD patients despite a lack of OH. Transcranial Doppler monitoring during head-up tilting may be a useful tool for evaluating dizziness in PD patients with or without OH. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:337-342, 2017. © 2017 Wiley Periodicals, Inc.

Cognitive and neuropsychiatric features of orthostatic tremor: A case-control comparison.

PubMed

Benito-León, Julián; Louis, Elan D; Puertas-Martín, Verónica; Romero, Juan Pablo; Matarazzo, Michele; Molina-Arjona, José Antonio; Domínguez-González, Cristina; Sánchez-Ferro, Álvaro

2016-02-15

Evidence suggests that the cerebellum could play a role in the pathophysiology of orthostatic tremor. The link between orthostatic tremor and the cerebellum is of interest, especially in light of the role the cerebellum plays in cognition, and it raises the possibility that orthostatic tremor patients could have cognitive deficits consistent with cerebellar dysfunction. Our aim was to examine whether orthostatic tremor patients had cognitive deficits and distinct personality profiles when compared with matched controls. Sixteen consecutive orthostatic tremor patients (65.7 ± 13.3 years) and 32 healthy matched controls underwent a neuropsychological battery and the Personality Assessment Inventory. In linear regression models, the dependent variable was each one of the neuropsychological test scores or the Personality Assessment Inventory subscales and the independent variable was orthostatic tremor vs. Adjusted for age in years, sex, years of education, comorbidity index, current smoker, and depressive symptoms, diagnosis (orthostatic tremor vs. healthy control) was associated with poor performance on tests of executive function, visuospatial ability, verbal memory, visual memory, and language tests, and on a number of the Personality Assessment Inventory subscales (somatic concerns, anxiety related disorders, depression, and antisocial features). Older-onset OT (>60 years) patients had poorer scores on cognitive and personality testing compared with their younger-onset OT counterparts. Orthostatic tremor patients have deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests involvement of frontocerebellar circuits. Cognitive impairment and personality disturbances could be disease-associated nonmotor manifestations of orthostatic tremor. Copyright © 2015 Elsevier B.V. All rights reserved.

Excessive pulse pressure response to standing in community population with orthostatic systolic hypertension.

PubMed

Xu, Jingsong; Zhou, Yueying; Cao, Kaiwu; Li, Juxiang; Tao, Xuehua; Zhang, Zhihong; Liu, Xin; Liu, Jiaqi; Su, Hai

2014-03-01

The postural change of pulse pressure (PP) in the persons with orthostatic hypertension (OHT) is unclear. This study included 2849 (65.0 ± 9.3 years) community participants. Blood pressures (BPs) in supine and standing positions were measured. The differences between upright and supine BP and PP were recorded as ΔBP and ΔPP. The criteria for OHT was ΔBP ≥10 mm Hg, for orthostatic hypotension (OH) was ≤-10 mm Hg and for orthostatic normotension (ONT) was -9 to 9 mm Hg. Fasting blood lipids and glucose were measured. The supine SBP of the sOHT group were similar to that of sONT group (140.9 ± 20.2 mm Hg vs 138.2 ± 19.7 mm Hg), but significantly lower than that of sOH group (151.9 ± 19.2 mm Hg; P < .05). Their PPs were 65.3 ± 15.9, 62.8 ± 14.7, and 71.1 ± 15.1 mm Hg, respectively, and with the similar group difference like SBP. When the position changed from supine to standing, the sOHT group showed PP rise, while sOH and sONT groups showed PP reduction (3.8 ± 7.1 mm Hg vs -17.0 ± 8.5 mm Hg and -5.8 ± 6.6 mm Hg; both P < .05). Thus, the standing PP in the sOHT group was significantly higher than in the sONT (69.1 ± 18.0 mm Hg vs 57.0 ± 15.8 mm Hg; P < .05) and in the sOH (54.2 ± 15.2 mm Hg; P < .05) groups. The postural PP profile varies with the postural responses of SBP. The sOHT group has obviously increased PP and significantly higher standing PP compared with the sONT group. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

L-NAME, a nitric oxide synthase inhibitor, as a potential countermeasure to post-suspension hypotension in rats

NASA Technical Reports Server (NTRS)

Bayorh, M. A.; Socci, R. R.; Watts, S.; Wang, M.; Eatman, D.; Emmett, N.; Thierry-Palmer, M.

2001-01-01

A large number of astronauts returning from spaceflight experience orthostatic hypotension. This hypotension may be due to overproduction of vasodilatory mediators, such as nitric oxide (NO) and prostaglandins. To evaluate the role of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we assessed the cardiovascular responses and vascular reactivity to 7-day 30 degrees tail-suspension and a subsequent 6 hr post-suspension period in conscious rats. After a pre-suspension reading, direct MAP and heart rate (HR) were measured daily and every 2 hrs post-suspension. The NO synthase inhibitor L-NAME (20 mg/kg, i.v.), or saline, were administered after the 7th day reading prior to release from suspension and at 2 and 4 hrs post-suspension. At 6 hrs post-suspension, vascular reactivity was assessed. While MAP did not change during the suspension period, it was reduced post-suspension. Heart rate was not significantly altered. L-NAME administration reversed the post-suspension reduction in MAP. In addition, the baroreflex sensitivity for heart rate was modified by L-NAME. Thus, the post-suspension reduction in MAP may be due to overproduction of NO and altered baroreflex activity.

Orthostatic intolerance: a disorder of young women

NASA Technical Reports Server (NTRS)

Ali, Y. S.; Daamen, N.; Jacob, G.; Jordan, J.; Shannon, J. R.; Biaggioni, I.; Robertson, D.

2000-01-01

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.

Orthostatic intolerance and motion sickness after parabolic flight

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Brown, T. E.; Wood, S. J.; Benavides, E. W.; Bondar, R. L.; Stein, F.; Moradshahi, P.; Harm, D. L.; Fritsch-Yelle, J. M.; Low, P. A.

2001-01-01

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Association between abnormal nocturnal blood pressure profile and dementia in Parkinson's disease.

PubMed

Tanaka, Ryota; Shimo, Yasushi; Yamashiro, Kazuo; Ogawa, Takashi; Nishioka, Kenya; Oyama, Genko; Umemura, Atsushi; Hattori, Nobutaka

2018-01-01

Circadian blood pressure alterations are frequently observed in Parkinson's disease, but the association between these changes and dementia in the condition remains unclear. Here, we assess the relationship between abnormal nocturnal blood pressure profiles and dementia in Parkinson's disease. We enrolled 137 patients with Parkinson's disease, who underwent 24 h ambulatory blood pressure monitoring, following cognitive and clinical assessment. Twenty-seven patients (19.7%) were diagnosed with dementia in this cohort. We observed significant associations of dementia with age, male gender, Hoehn-Yahr (H-Y) stage, diabetes mellitus, history of stroke, presence of cerebrovascular lesions on MRI, and orthostatic hypotension. Univariate logistic regression analysis showed that among the patterns of nocturnal blood pressure profiles, the riser pattern was significantly associated with dementia (OR 11.6, 95%CI: 2.14-215.0, P < 0.01), and this trend was observed after adjusting for all confounding factors except orthostatic hypotension (OR 19.2, 95%CI: 1.12-1960.3, P = 0.04). However, coexistence of a riser pattern and orthostatic hypotension was related to a higher prevalence of dementia (45.2%) than was a riser pattern alone (9.5%). Furthermore, coexistence of a riser pattern and orthostatic hypotension was significantly more associated with dementia than was a riser pattern alone, even after adjusting for confounders (OR 1625.1, 95%CI: 21.9-1343909.5, P < 0.01). Our results suggest a relationship between a riser pattern coexisting with orthostatic hypotension and dementia in Parkinson's disease. Further prospective studies are warranted to investigate whether abnormal nocturnal blood pressure profiles predict dementia in Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fitness, autonomic regulation and orthostatic tolerance

NASA Technical Reports Server (NTRS)

Buckey, Jay C.

1991-01-01

Work on this grant has consisted of two major studies of cardiovascular regulation in athletes along with several smaller supporting studies. This summary will give a brief overview of two major studies, and then conclude with an analysis of what the findings from these studies mean practically, and how they can be applied to current problems with post-flight orthostatic intolerance. The first study addresses a cross-sectional analysis of orthostatic intolerance in highly aerobically trained individuals; the second addresses ventricular pressure/volume relationships in athletes.

Cardiovascular Autonomic Dysfunction in Patients with Drug-Induced Parkinsonism

PubMed Central

Ryu, Dong-Woo; Oh, Ju-Hee; Lee, Yang-Hyun; Park, Sung-Jin; Jeon, Kipyung; Lee, Jong-Yun; Ho, Seong Hee; So, Jungmin; Im, Jin Hee; Lee, Kwang-Soo

2017-01-01

Background and Purpose Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. Methods This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring. Results Orthostatic hypotension was more frequent in patients with PD or DIP than in healthy controls. In DIP, orthostatic hypotension was associated with the underlying psychiatric diseases and neuroleptics use, whereas prokinetics were not related to orthostatic hypotension. The supine blood pressure, nighttime blood pressure, and nocturnal blood pressure dipping did not differ significantly between the DIP and control groups. Supine hypertension and nocturnal hypertension were more frequent in PD patients than in controls. Conclusions The included DIP patients frequently exhibited orthostatic hypotension that was associated with the underlying diseases as well as the nature of and exposure time to the offending drugs. Clinicians should individualize the manifestations of DIP according to underlying diseases as well as the action mechanism of and exposure time to each offending drug. PMID:27730767

Sympathovagal response to orthostatism in overt and in subclinical hyperthyroidism.

PubMed

Goichot, B; Brandenberger, G; Vinzio, S; Perrin, A E; Geny, B; Schlienger, J L; Simon, C

2004-04-01

Heart rate variability (HRV) is a measure of the physiological variation of R-R intervals, reflecting the sympathovagal balance. In both overt and subclinical hyperthyroidism, a relative increase in sympathetic activity has been demonstrated, mainly due to a decrease in vagal activity. The modifications of HRV during orthostatism in normal subjects resemble those seen in hyperthyroidism. We have studied the response of 19 patients with overt hyperthyroidism and 12 with subclinical hyperthyroidism during orthostatism using HRV and compared the results to those of 32 healthy controls. In the three groups, the R-R intervals decreased in the same proportion after orthostatism. The low frequency power (LF)/[LF + high frequency power (HF)] ratio, which reflects the sympathetic tone, also increased in the same proportion in the three groups. However, the mechanisms of the modulation of the sympathovagal balance during orthostatism were different among the three groups. In controls, the relative increase of sympathetic tone after orthostatism was due principally to a decrease in vagal tone (reflected by decreased power in the HF band), while in overt hyperthyroidism, where the power in the HF band was already minimal in the lying position, there was a clear increase in the LF band power during orthostatism. The results were intermediate in the subclinical hyperthyroidism group, reflecting a continuum of effects of the thyroid hormone excess on the autonomic nervous system. Our study shows that despite an apparent normal cardiovascular adaptation to orthostatism in hyperthyroidism, the modulation of the autonomic nervous system is profoundly modified.

Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial).

PubMed

Anstey, Matthew H; Wibrow, Bradley; Thevathasan, Tharusan; Roberts, Brigit; Chhangani, Khushi; Ng, Pauline Yeung; Levine, Alexander; DiBiasio, Alan; Sarge, Todd; Eikermann, Matthias

2017-03-21

Patients admitted to intensive care units (ICU) are often treated with intravenous (IV) vasopressors. Persistent hypotension and dependence on IV vasopressors in otherwise resuscitated patients lead to delay in discharge from ICU. Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension. This trial aims to evaluate whether oral administration of midodrine is an effective adjunct to standard therapy to reduce the duration of IV vasopressor treatment, and allow earlier discharge from ICU and hospital. The MIDAS trial is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial being conducted in the USA and Australia. We are targeting 120 patients. Adult patients admitted to the ICU who are resuscitated and otherwise stable on low dose IV vasopressors for at least 24 h will be considered for recruitment. Participants will be randomized to receive midodrine (20 mg) or placebo three times a day, in addition to standard care. The primary outcome is time (hours) from initiation of midodrine or placebo to discontinuation of IV vasopressors. Secondary outcomes include time (hours) from ICU admission to discharge readiness, ICU length of stay (LOS) (days), hospital LOS (days), rates of ICU readmission, and rates of adverse events related to midodrine administration. Midodrine is approved by the Food and Drug Administration (FDA) for the treatment of symptomatic orthostatic hypotension. In August 2010, FDA proposed to withdraw approval of midodrine because of lack of studies that verify the clinical benefit of the drug. We obtained Investigational New Drug (IND 113,330) approval to study its effects in critically ill patients who require IV vasopressors but are otherwise ready for discharge from the ICU. A pilot observational study in a cohort of surgical ICU patients showed that the rate of decline in vasopressor requirements increased after initiation of midodrine treatment. We

Normal Reactions to Orthostatic Stress in Rett Syndrome

ERIC Educational Resources Information Center

Larsson, Gunilla; Julu, Peter O. O.; Engerstrom, Ingegerd Witt; Sandlund, Marlene; Lindstrom, Britta

2013-01-01

The aim of this study was to investigate orthostatic reactions in females with Rett syndrome (RTT), and also whether the severity of the syndrome had an impact on autonomic reactions. Based on signs of impaired function of the central autonomic system found in RTT, it could be suspected that orthostatic reactions were affected. The orthostatic…

Orthostatic Intolerance and Motion Sickness After Parabolic Flight

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Brown, Troy E.; Wood, Scott J.; Benavides, Edgar W.; Bondar, Roberta L.; Stein, Flo; Moradshahi, Peyman; Harm, Deborah L.; Low, Phillip A.

1999-01-01

Orthostatic intolerance is common in astronauts after prolonged space flight. However, the "push-pull effect" in military aviators suggests that brief exposures to transitions between hypo- and hypergravity are sufficient to induce untoward autonomic cardiovascular physiology in susceptible individuals. We therefore investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy test subjects before and after a seated 2-hr parabolic flight. At the same time, we also investigated relationships between parabolic flight-induced vomiting and changes in orthostatic and autonomic cardiovascular function. After parabolic flight, 8 of 16 subjects could not tolerate a 30-min upright tilt test, compared to 2 of 16 before flight. Whereas new intolerance in non-Vomiters resembled the clinical postural tachycardia syndrome (POTS), new intolerance in Vomiters was characterized by comparatively isolated upright hypocapnia and cerebral vasoconstriction. As a group, Vomiters also had evidence for increased postflight fluctuations in efferent vagal-cardiac nerve traffic occurring independently of any superimposed change in respiration. Results suggest that syndromes of orthostatic intolerance resembling those occurring after space flight can occur after a brief (i.e., 2-hr) parabolic flight.

Crisis management during anaesthesia: hypotension.

PubMed

Morris, R W; Watterson, L M; Westhorpe, R N; Webb, R K

2005-06-01

Hypotension is commonly encountered in association with anaesthesia and surgery. Uncorrected and sustained it puts the brain, heart, kidneys, and the fetus in pregnancy at risk of permanent or even fatal damage. Its recognition and correction is time critical, especially in patients with pre-existing disease that compromises organ perfusion. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for hypotension, in the management of hypotension when it occurs in association with anaesthesia. Reports of hypotension during anaesthesia were extracted and studied from the first 4000 incidents reported to the Australian Incident Monitoring Study (AIMS). The potential performance of the COVER ABCD algorithm and the sub-algorithm for hypotension was compared with the actual management as reported by the anaesthetist involved. There were 438 reports that mentioned hypotension, cardiovascular collapse, or cardiac arrest. In 17% of reports more than one cause was attributed and 550 causative events were identified overall. The most common causes identified were drugs (26%), regional anaesthesia (14%), and hypovolaemia (9%). Concomitant changes were reported in heart rate or rhythm in 39% and oxygen saturation or ventilation in 21% of reports. Cardiac arrest was documented in 25% of reports. As hypotension was frequently associated with abnormalities of other vital signs, it could not always be adequately addressed by a single algorithm. The sub-algorithm for hypotension is adequate when hypotension occurs in association with sinus tachycardia. However, when it occurs in association with bradycardia, non-sinus tachycardia, desaturation or signs of anaphylaxis or other problems, the sub-algorithm for hypotension recommends cross referencing to other relevant sub-algorithms. It was considered that, correctly applied, the core algorithm COVER ABCD would have diagnosed 18% of cases and led to resolution in

Utility of Time and Frequency Domain Parameters of Heart Rate Variability in the Context of Autonomic Disorders Characterized by Orthostatic Dysfunction.

PubMed

Baker, Jacquie; Racosta, Juan M; Balint, Brittany; Kimpinski, Kurt

2018-03-01

The clinical significance of heart rate variability in the context of autonomic dysfunction continues to be a matter of debate. A consensus is lacking on the best heart rate variability measures for clinical purposes. Therefore, the purpose of this study was to investigate the utility of heart rate variability parameters in healthy versus autonomic dysfunction. Healthy young (n = 134), healthy older (n = 32), and patients with mild (postural tachycardia syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34) autonomic dysfunction were included. Time and frequency parameters during baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB) were compared. Cardiovagal time parameters were significantly reduced during HUT in healthy young and postural tachycardia syndrome (P < 0.001). Healthy young had significantly higher time parameters during baseline, HUT, and HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate (HR) (61.4 ± 9.0 bpm vs. 76.8 ± 13.6 bpm; P < 0.001) and a smaller [INCREMENT]HR during HUT (32.8 ± 10.5 bpm vs. 44.4 ± 13.3 bpm; P < 0.001). Time parameters increased in young and postural tachycardia syndrome during HRDB, which was characterized by a nonsignificant difference in [INCREMENT]HR between both groups. Time parameters were significantly higher in healthy old versus neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During HUT, only the SD of all normal RR intervals remained significantly higher. Heart rate changes corroborated these findings. Resting HR was significantly lower in healthy older (62.6 ± 11.0 bpm vs. 70.7 ± 12.4 bpm), and [INCREMENT]HR during HRDB was significantly higher (15.9 ± 9.2 bpm vs. 3.9 ± 4.2 bpm; P < 0.001). During HUT, [INCREMENT]HR showed no significant differences. Time domain parameters of heart rate variability have a greater utility than frequency parameters in clinical autonomic disorders.

Mathematical modeling of human cardiovascular system for simulation of orthostatic response

NASA Technical Reports Server (NTRS)

Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

1992-01-01

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

Orthostatic blood pressure regulation predicts classroom effort in children.

PubMed

Carapetian, Stephanie; Siedlarz, Monika; Jackson, Sandra; Perlmuter, Lawrence C

2008-04-01

The increase in orthostatic systolic blood pressure associated with the shift in posture from lying to standing requires several compensatory mechanisms to ensure adequate cerebral perfusion. Decreased efficiency in the various mechanisms controlling orthostatic blood pressure regulation can result in dizziness, lightheadedness, and syncope. The degree of effectiveness of orthostatic systolic blood pressure regulation (OBPR) serves as a marker for a variety of problems including fatigue, depression, anxiety, reduced attention, impulsive behavior and reduced volition. In normal children, an insufficient increase in systolic blood pressure in response to upright posture is predictive of mild cognitive and affective problems. The present study examined orthostatic systolic blood pressure regulation in relation to yearlong teachers' evaluations of academic grades and effort in 7-11 year old children. Poorer systolic blood pressure regulation in response to orthostasis was associated with reduced levels of classroom effort, while academic grades were spared. Converging evidence from clinical as well as experimental studies suggests that the linkage between (OBPR) and effort may be partially mediated by sympathetic dysfunction, altered release of neurotransmitters, or reduced cerebral blood flow.

Hypotensive effect of alpha-lipoic acid after a single administration in rats.

PubMed

Dudek, Magdalena; Razny, Katarzyna; Bilska-Wilkosz, Anna; Iciek, Malgorzata; Sapa, Jacek; Wlodek, Lidia; Filipek, Barbara

2016-05-01

The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter. Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

[Clinical characteristics of benign paroxysmal vertigo of childhood (BPVC)].

PubMed

Goto, Fumiyuki; Morimoto, Noriko; Ohara, Takuya; Honmura, Tomoko; Taiji, Hidenobu

2011-06-01

Pediatric subjects with vertigo or dizziness are rare in Japan, although considerable statistical data accumulated, mostly indicating that orthostatic hypotension is the most frequent clinical symptoms in Japan, as opposed to Benign paroxysmal vertigo of childhood (BPVC), reported to be most frequent abroad. We studied BPVC incidence and clinical features. Subjects were 5 boys and 7 girls aged 4 to 15 years old (average +/- sd 9.5 +/- 3.1 years). The predominant diagnosis was BPVC in 8, orthostatic hypotension in 6, labyrinthitis in 2, and delayed endolymphatic hydrops, and conversion disorder in 1 case each. BPVC was most common. All subjects with BPVC had a history or a family history of migraine. Based on BPVC diagnostic criteria, subjects had neither organic nor functional abnormalities. Information is thus required on attack, injury, and personal or family migraine history to determine a final diagnosis. Note that subjects with BPVC have high orthostatic hypotension. These statistics indicate the importance of diagnostic BPVC criteria in pediatric subjects with dizziness or vertigo.

Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome.

PubMed

Roma, Maria; Marden, Colleen L; De Wandele, Inge; Francomano, Clair A; Rowe, Peter C

2018-03-05

To review the association between orthostatic intolerance syndromes and both joint hypermobility and Ehlers-Danlos syndrome, and to propose reasons for identifying hereditary connective tissue disorders in those with orthostatic intolerance in the context of both clinical care and research. We searched the published peer-reviewed medical literature for papers reporting an association between joint hypermobility or Ehlers-Danlos syndrome and orthostatic intolerance. We identified 10 relevant papers. Although methodological variability between studies introduces some limitations, the published literature consistently identifies a significantly higher prevalence of orthostatic intolerance symptoms in patients with joint hypermobility or Ehlers-Danlos syndrome than in healthy controls, and a significantly higher prevalence of cardiovascular and autonomic abnormalities both at rest and during orthostatic challenge. Postural tachycardia syndrome is the most commonly recognized circulatory disorder. The severity of orthostatic symptoms in those with EDS correlates with impairments in quality of life. There is a strong association between several forms of cardiovascular dysfunction, most notably postural tachycardia syndrome, and joint hypermobility or Ehlers-Danlos syndrome. We propose that recognition of joint hypermobility and Ehlers-Danlos syndrome among those with orthostatic intolerance syndromes has the potential to improve clinical care and the validity of research findings. Copyright © 2018 Elsevier B.V. All rights reserved.

Orthostatic intolerance predicts mild cognitive impairment: incidence of mild cognitive impairment and dementia from the Swedish general population cohort Good Aging in Skåne

PubMed Central

Elmståhl, Sölve; Widerström, Elisabet

2014-01-01

Introduction Contradictory results have been reported on the relationship between orthostatic hypotension (OH) and mild cognitive impairment (MCI). Objective To study the incidence of MCI and dementia and their relationship to OH and subclinical OH with orthostatic symptoms (orthostatic intolerance). Study design and setting This study used a prospective general population cohort design and was based on data from the Swedish Good Aging in Skåne study (GÅS-SNAC), they were studied 6 years after baseline of the present study, with the same study protocol at baseline and at follow-up. The study sample comprised 1,480 randomly invited subjects aged 60 to 93 years, and had a participation rate of 82% at follow-up. OH test included assessment of blood pressure and symptoms of OH. Results The 6-year incidence of MCI was 8%, increasing from 12.1 to 40.5 per 1,000 person-years for men and 6.9 to 16.9 per 1,000 person-years for women aged 60 to >80 years. The corresponding 6-year incidence of dementia was 8%. Orthostatic intolerance during uprising was related to risk for MCI at follow-up (odds ratio [OR] =1.84 [1.20–2.80][95% CI]), adjusted for age and education independently of blood pressure during testing. After stratification for hypertension (HT), the corresponding age-adjusted OR for MCI in the non-HT group was 1.71 (1.10–2.31) and 1.76 (1.11–2.13) in the HT group. Among controls, the proportion of those with OH was 16%; those with MCI 24%; and those with dementia 31% (age-adjusted OR 1.93 [1.19–3.14]). Conclusion Not only OH, but also symptoms of OH, seem to be a risk factor for cognitive decline and should be considered in the management of blood pressure among the elderly population. PMID:25429211

Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

PubMed Central

Keller, David M.; Low, David A.; Davis, Scott L.; Hastings, Jeff

2011-01-01

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ∼34°C and skin surface cooling ∼12–15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ∼30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals. PMID:21454746

Effect of fluid countermeasures of varying osmolarity on cardiovascular responses to orthostatic stress

NASA Technical Reports Server (NTRS)

Davis, John E.

1989-01-01

Current operational procedures for shuttle crewmembers include the ingestion of a fluid countermeasure approximately 2 hours before reentry into the earth's gravitational field. The ingestion of the fluid countermeasure is thought to restore plasma volume and improve orthostatic responses upon reentry. The present countermeasure consists of ingesting salt tablets and water to achieve an isotonic solution. It has yet to be determined whether this is the optimal drink to restore orthostatic tolerance. It is also not known whether the drink solution is effective in increasing plasma volume. The purpose here is to evaluate the effectiveness of drink solutions of different osmolarity on restoring plasma volume and orthostatic responses. A hypertonic drink solution was more effective in restoring plasma volume after dehydration than an isotonic solution. However, there were no differences in their effects on an orthostatic challenge. These data suggest that the plasma volume differences produced in this study were not sufficient to produce differences in the cardiovascular responses to an orthostatic challenge, or there are other changes that occur during space flight that are more important in determining orthostatic intolerance.

Predictors of intraoperative hypotension and bradycardia.

PubMed

Cheung, Christopher C; Martyn, Alan; Campbell, Norman; Frost, Shaun; Gilbert, Kenneth; Michota, Franklin; Seal, Douglas; Ghali, William; Khan, Nadia A

2015-05-01

Perioperative hypotension and bradycardia in the surgical patient are associated with adverse outcomes, including stroke. We developed and evaluated a new preoperative risk model in predicting intraoperative hypotension or bradycardia in patients undergoing elective noncardiac surgery. Prospective data were collected in 193 patients undergoing elective, noncardiac surgery. Intraoperative hypotension was defined as systolic blood pressure <90 mm Hg for >5 minutes or a 35% decrease in the mean arterial blood pressure. Intraoperative bradycardia was defined as a heart rate of <60 beats/min for >5 minutes. A logistic regression model was developed for predicting intraoperative hypotension or bradycardia with bootstrap validation. Model performance was assessed using area under the receiver operating curves and Hosmer-Lemeshow tests. A total of 127 patients developed hypotension or bradycardia. The average age of participants was 67.6 ± 11.3 years, and 59.1% underwent major surgery. A final 5-item score was developed, including preoperative Heart rate (<60 beats/min), preoperative hypotension (<110/60 mm Hg), Elderly age (>65 years), preoperative renin-Angiotensin blockade (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers), Revised cardiac risk index (≥3 points), and Type of surgery (major surgery), entitled the "HEART" score. The HEART score was moderately predictive of intraoperative bradycardia or hypotension (odds ratio, 2.51; 95% confidence interval, 1.79-3.53; C-statistic, 0.75). Maximum points on the HEART score were associated with an increased likelihood ratio for intraoperative bradycardia or hypotension (likelihood ratio, +3.64). The 5-point HEART score was predictive of intraoperative hypotension or bradycardia. These findings suggest a role for using the HEART score to better risk-stratify patients preoperatively and may help guide decisions on perioperative management of blood pressure and heart rate

Relation of blood volume and blood pressure in orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1998-01-01

A complex but crucial relationship exists between blood volume and blood pressure in human subjects; it has been recognized that in essential hypertension, renovascular hypertension, and pheochromocytoma, the relationship between plasma volume and diastolic blood pressure is an inverse one. This phenomenon has not been studied in individuals with low normal and reduced blood pressures. Orthostatic intolerance is a commonly encountered abnormality in blood pressure regulation often associated with tachycardia in the standing position. Most of these patients have varying degrees of reduced blood volume. We tested the hypothesis that the relationship previously found between plasma volume and diastolic blood pressure in pressor states would also hold in orthostatic intolerance. We studied 16 patients with a history of symptomatic orthostatic intolerance associated with an elevation in plasma norepinephrine in the upright posture and hypovolemia in 9 patients and normovolemia in 7 patients. Our studies demonstrate an inverse relationship between plasma volume and diastolic blood pressure in patients with orthostatic intolerance. This finding also holds for the change in diastolic blood pressure in response to upright posture. In this relationship, patients with orthostatic intolerance with high plasma norepinephrine resemble those with essential hypertension, renovascular hypertension, and pheochromocytoma. We conclude that in a variety of conditions at both ends of the blood pressure spectrum, the seemingly paradoxical association of hypovolemia and diastolic blood pressure is preserved.

Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise.

PubMed

Akerman, Ashley P; Lucas, Samuel J E; Katare, Rajesh; Cotter, James D

2017-01-01

Exercise and exogenous heat each stimulate multiple adaptations, but their roles are not well delineated, and that of the related stressor, dehydration, is largely unknown. While severe and prolonged hypohydration potentially "silences" the long-term heat acclimated phenotype, mild and transient dehydration may enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis that exogenous heat stress and dehydration additively potentiate acute (24 h) cardiovascular and hematological outcomes following exercise. In a randomized crossover study, 10 physically-active volunteers (mean ± SD: 173 ± 11 cm; 72.1 ± 11.5 kg; 24 ± 3 year; 6 females) completed three trials of 90-min orthostatically-stressful calisthenics, in: (i) temperate conditions (22°C, 50% rh, no airflow; CON); (ii) heat (40°C, 60% rh) whilst euhydrated (HEAT), and (iii) heat with dehydration (no fluid ~16 h before and during exercise; HEAT+DEHY). Using linear mixed effects model analyses, core temperature (T CORE ) rose 0.7°C more in HEAT than CON (95% CL: [0.5, 0.9]; p < 0.001), and another 0.4°C in HEAT+DEHY ([0.2, 0.5]; p < 0.001, vs. HEAT). Skin temperature also rose 1.2°C more in HEAT than CON ([0.6, 1.8]; p < 0.001), and similarly to HEAT+DEHY ( p = 0.922 vs. HEAT). Peak heart rate was 40 b·min -1 higher in HEAT than in CON ([28, 51]; p < 0.001), and another 15 b·min -1 higher in HEAT+DEHY ([3, 27]; p = 0.011, vs. HEAT). Mean arterial pressure at 24-h recovery was not consistently below baseline after CON or HEAT ( p ≥ 0.452), but was reduced 4 ± 1 mm Hg after HEAT+DEHY ([0, 8]; p = 0.020 vs. baseline). Plasma volume at 24 h after exercise increased in all trials; the 7% increase in HEAT was not reliably more than in CON (5%; p = 0.335), but was an additional 4% larger after HEAT+DEHY ([1, 8]; p = 0.005 vs. HEAT). Pooled-trial correlational analysis showed the rise in T CORE predicted the hypotension ( r = -0.4) and plasma volume expansion ( r = 0.6) at 24 h, with

Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise

PubMed Central

Akerman, Ashley P.; Lucas, Samuel J. E.; Katare, Rajesh; Cotter, James D.

2017-01-01

Exercise and exogenous heat each stimulate multiple adaptations, but their roles are not well delineated, and that of the related stressor, dehydration, is largely unknown. While severe and prolonged hypohydration potentially “silences” the long-term heat acclimated phenotype, mild and transient dehydration may enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis that exogenous heat stress and dehydration additively potentiate acute (24 h) cardiovascular and hematological outcomes following exercise. In a randomized crossover study, 10 physically-active volunteers (mean ± SD: 173 ± 11 cm; 72.1 ± 11.5 kg; 24 ± 3 year; 6 females) completed three trials of 90-min orthostatically-stressful calisthenics, in: (i) temperate conditions (22°C, 50% rh, no airflow; CON); (ii) heat (40°C, 60% rh) whilst euhydrated (HEAT), and (iii) heat with dehydration (no fluid ~16 h before and during exercise; HEAT+DEHY). Using linear mixed effects model analyses, core temperature (TCORE) rose 0.7°C more in HEAT than CON (95% CL: [0.5, 0.9]; p < 0.001), and another 0.4°C in HEAT+DEHY ([0.2, 0.5]; p < 0.001, vs. HEAT). Skin temperature also rose 1.2°C more in HEAT than CON ([0.6, 1.8]; p < 0.001), and similarly to HEAT+DEHY (p = 0.922 vs. HEAT). Peak heart rate was 40 b·min−1 higher in HEAT than in CON ([28, 51]; p < 0.001), and another 15 b·min−1 higher in HEAT+DEHY ([3, 27]; p = 0.011, vs. HEAT). Mean arterial pressure at 24-h recovery was not consistently below baseline after CON or HEAT (p ≥ 0.452), but was reduced 4 ± 1 mm Hg after HEAT+DEHY ([0, 8]; p = 0.020 vs. baseline). Plasma volume at 24 h after exercise increased in all trials; the 7% increase in HEAT was not reliably more than in CON (5%; p = 0.335), but was an additional 4% larger after HEAT+DEHY ([1, 8]; p = 0.005 vs. HEAT). Pooled-trial correlational analysis showed the rise in TCORE predicted the hypotension (r = −0.4) and plasma volume expansion (r = 0.6) at 24 h, with

Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III.

PubMed

Cheng, Jem L; Au, Jason S; Guzman, Juan C; Morillo, Carlos A; MacDonald, Maureen J

2017-04-01

The cardiovascular profile of postural orthostatic tachycardia syndrome + Ehlers-Danlos syndrome hypermobility type (POTS + EDSIII) has not been described, despite suggestions that it plays a role in orthostatic intolerance. We studied nine individuals diagnosed with POTS + EDSIII and found that the arterial stiffness and cardiac profiles of patients with POTS + EDSIII were comparable to those of age- and sex-matched controls, suggesting an alternate explanation for orthostatic intolerance.

Characterizing Orthostatic Tremor Using a Smartphone Application.

PubMed

Balachandar, Arjun; Fasano, Alfonso

2017-01-01

Orthostatic tremor is one of the few tremor conditions requiring an electromyogram for definitive diagnosis since leg tremor might not be visible to the naked eye. An iOS application (iSeismometer, ObjectGraph LLC, New York) using an Apple iPhone 5 (Cupertino, CA, USA) inserted into the patient's sock detected a tremor with a frequency of 16.4 Hz on both legs. The rapid and straightforward accelerometer-based recordings accomplished in this patient demonstrate the ease with which quantitative analysis of orthostatic tremor can be conducted and, importantly, demonstrates the potential application of this approach in the assessment of any lower limb tremor.

Leg blood pressure measured in orthostatic posture is associated with left ventricular mass in normotensive subjects.

PubMed

Gemignani, Tiago; Matos-Souza, José R; Franchini, Kleber G; Nadruz, Wilson

2012-10-01

Changing from a supine to an orthostatic posture is associated with substantial increments in leg blood pressure (BP) levels, which could ultimately influence the hemodynamic burden imposed on the heart. This study investigated the relationship between brachial and leg BP measurements and the left cardiac chamber's structure and assessed the role of body posture changes in this regard. One hundred and thirty normotensive, nondiabetic, nonsmoking, normolipemic subjects were evaluated by a clinical history, anthropometry, the analysis of metabolic parameters, echocardiography, and the measurement of BP in the arm and the calf in both supine and orthostatic positions. Significant correlation coefficients between the leg BP measurements and the cardiac structure were detected, especially between the orthostatic pulse pressure (PP) and the left ventricular (LV) wall thickness (r = 0.38; P < 0.001), the orthostatic PP and the LV mass (r = 0.37; P < 0.001), and the orthostatic systolic BP (SBP) and the left atrial size (r = 0.35; P < 0.001). Stepwise and standard regression analysis adjusted for brachial BP and anthropometric and metabolic variables confirmed that the leg orthostatic PP was independently related to the LV wall thickness and mass. Moreover, the leg orthostatic SBP was associated with the left atrial dimension even after adding the LV mass to the statistical models. Finally, triglyceride levels and body surface area showed significant relationship with leg orthostatic PP and SBP, whereas brachial orthostatic PP and SBP were only associated with age and anthropometric variables. Orthostatic leg BP is independently associated with the cardiac structure in normotensive subjects.

Exercise training - Blood pressure responses in subjects adapted to microgravity

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

1991-01-01

Conventional endurance exercise training that involves daily workouts of 1-2 hr duration during exposure to microgravity has not proven completely effective in ameliorating postexposure orthostatic hypotension. Single bouts of intense exercise have been shown to increase plasma volume and baroreflex sensitivity in ambulatory subjects through 24 hr postexercise and to reverse decrements in maximal oxygen uptake and syncopal episodes following exposure to simulated microgravity. These physiological adaptations to acute intense exercise were opposite to those observed following exposure to microgravity. These results suggest that the 'exercise training' stimulus used to prevent orthostatic hypotension induced by microgravity may be specific and should be redefined to include single bouts of maximal exercise which may provide an acute effective countermeasure against postflight hypotension.

Computational modeling of cardiovascular response to orthostatic stress

NASA Technical Reports Server (NTRS)

Heldt, Thomas; Shim, Eun B.; Kamm, Roger D.; Mark, Roger G.

2002-01-01

The objective of this study is to develop a model of the cardiovascular system capable of simulating the short-term (< or = 5 min) transient and steady-state hemodynamic responses to head-up tilt and lower body negative pressure. The model consists of a closed-loop lumped-parameter representation of the circulation connected to set-point models of the arterial and cardiopulmonary baroreflexes. Model parameters are largely based on literature values. Model verification was performed by comparing the simulation output under baseline conditions and at different levels of orthostatic stress to sets of population-averaged hemodynamic data reported in the literature. On the basis of experimental evidence, we adjusted some model parameters to simulate experimental data. Orthostatic stress simulations are not statistically different from experimental data (two-sided test of significance with Bonferroni adjustment for multiple comparisons). Transient response characteristics of heart rate to tilt also compare well with reported data. A case study is presented on how the model is intended to be used in the future to investigate the effects of post-spaceflight orthostatic intolerance.

Deep brain stimulation improves orthostatic regulation of patients with Parkinson disease.

PubMed

Stemper, B; Beric, A; Welsch, G; Haendl, T; Sterio, D; Hilz, M J

2006-11-28

To evaluate whether subthalamic nucleus (STN) stimulation has an effect on the orthostatic regulation of patients with Parkinson disease (PD), we studied cardiovascular regulation during on and off phases of STN stimulation. We examined 14 patients with PD (mean age 58.1 +/- 5.8 years, 4 women, 10 men) with bilateral STN stimulators. Patients underwent 3 minutes of head-up tilt (HUT) testing during STN stimulation and after 90 minutes interruption of stimulation. We monitored arterial blood pressure (BP), RR intervals (RRI), respiration, and skin blood flow (SBF). Baroreflex sensitivity (BRS) was assessed as the square root of the ratio of low-frequency power of RRI to the low-frequency power of systolic BP for coherences above 0.5. During the on phase of the STN stimulation, HUT induced no BP decrease, a significant tachycardia, and a significant decrease of SBF. During the off phase of stimulation, HUT resulted in significant decreases in BPsys and RRI and only a slight SBF decrease. HUT induced no change of BRS during stimulation, but lowered BRS when the stimulator was off (p < 0.05). STN stimulation of patients with PD increases peripheral vasoconstriction and BRS and stabilizes BP, thereby improving postural hypotension in patients with PD. The results indicate that STN stimulation not only alleviates motor deficits but also influences autonomic regulation in patients with PD.

Postural Orthostatic Tachycardia Syndrome during pregnancy: A systematic review of the literature.

PubMed

Morgan, Kate; Chojenta, Catherine; Tavener, Meredith; Smith, Angela; Loxton, Deb

2018-05-09

Postural Orthostatic Tachycardia Syndrome is most commonly seen in women of child bearing age, however little is known about its effects in pregnancy. A systematic review was conducted in March 2015 and updated in February 2018. Medline, Embase, PsychInfo, CINHAL, and the Cochrane Library were searched from database inception. The ClinicalTrials.gov site and bibliographies were searched. MeSH and Emtree headings and keywords included; Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, and were combined with pregnancy and pregnancy related subject headings and keywords. Searches were limited to English. Eligible articles contained key words within the title and or abstract. Articles were excluded if Postural Orthostatic Tachycardia Syndrome was not pre-existing. Eleven articles were identified as eligible for inclusion. Studies were appraised using the PRISMA 2009 guidelines. The overall quality of evidence was poor using the NHMRC Evidence Grading Matrix, which was attributed to small sample sizes and mostly observational studies, emphasizing the need for future high quality research. Findings in this review must be used with caution due to the poor quality of the literature available. Postural Orthostatic Tachycardia Syndrome should not be a contraindication to pregnancy. Symptom course is variable during pregnancy and the post-partum period. Continuing pre-conception medication may help symptoms, with no significant risks reported. Obstetric complications, not Postural Orthostatic Tachycardia Syndrome, should dictate mode of delivery. Postural Orthostatic Tachycardia Syndrome did not appear to affect the rate of adverse events. These results are important in determining appropriate management and care in this population. Copyright © 2018 Elsevier B.V. All rights reserved.

Neural autonomic control in orthostatic intolerance.

PubMed

Furlan, Raffaello; Barbic, Franca; Casella, Francesco; Severgnini, Giorgio; Zenoni, Luca; Mercieri, Angelo; Mangili, Ruggero; Costantino, Giorgio; Porta, Alberto

2009-10-01

Inability to maintain the upright position is manifested by a number of symptoms shared by either human pathophysiology and conditions following weightlessness or bed rest. Alterations of the neural sympathetic cardiovascular control have been suggested to be one of the potential underlying etiopathogenetic mechanisms in these conditions. We hypothesize that the study of the autonomic profile of human orthostatic intolerance syndromes may furnish a valuable insight into the complexity of the sympathetic alterations leading to a reduced gravitational tolerance. In the present paper we describe abnormalities both in the magnitude and in the pattern of the sympathetic neural firing observed in patients affected by orthostatic intolerance, attending the upright position. Also, we discuss similarity and differences in the neural sympathetic mechanisms regulating the cardiovascular system during the gravitational stimulus both in clinical syndromes and in subjects returning from space.

Is there room for non-dopaminergic treatment in Parkinson disease?

PubMed

Lieberman, Abraham; Krishnamurthi, Narayanan

2013-02-01

Although levodopa and dopaminergic drugs remain the mainstay of therapy for the motor symptoms of Parkinson disease (PD), they fail to address many of the non-motor symptoms of PD including orthostatic hypotension, freezing of gait (FOG) and difficulty with balance, drug-induced paranoia and hallucinations, and drug-induced dyskinesias. Droxidopa, a drug that increases norepinephrine, treats orthostatic hypotension, cholinomimetic drugs sometimes help with FOG and difficulty with balance, pimavanserin, a drug that blocks serotonin receptors, treats paranoia and hallucinations, and anti-glutaminergic drugs treat dyskinesias. Thus, there are ample opportunities for non-dopaminergic drugs in PD.

Pathological ponto-cerebello-thalamo-cortical activations in primary orthostatic tremor during lying and stance.

PubMed

Schöberl, Florian; Feil, Katharina; Xiong, Guoming; Bartenstein, Peter; la Fougére, Christian; Jahn, Klaus; Brandt, Thomas; Strupp, Michael; Dieterich, Marianne; Zwergal, Andreas

2017-01-01

Primary orthostatic tremor is a rare neurological disease characterized mainly by a high frequency tremor of the legs while standing. The aim of this study was to identify the common core structures of the oscillatory circuit in orthostatic tremor and how it is modulated by changes of body position. Ten patients with orthostatic tremor and 10 healthy age-matched control subjects underwent a standardized neurological and neuro-ophthalmological examination including electromyographic and posturographic recordings. Task-dependent changes of cerebral glucose metabolism during lying and standing were measured in all subjects by sequential 18 F-fluorodeoxyglucose-positron emission tomography on separate days. Results were compared between groups and conditions. All the orthostatic tremor patients, but no control subject, showed the characteristic 13-18 Hz tremor in coherent muscles during standing, which ceased in the supine position. While lying, patients had a significantly increased regional cerebral glucose metabolism in the pontine tegmentum, the posterior cerebellum (including the dentate nuclei), the ventral intermediate and ventral posterolateral nucleus of the thalamus, and the primary motor cortex bilaterally compared to controls. Similar glucose metabolism changes occurred with clinical manifestation of the tremor during standing. The glucose metabolism was relatively decreased in mesiofrontal cortical areas (i.e. the medial prefrontal cortex, supplementary motor area and anterior cingulate cortex) and the bilateral anterior insula in orthostatic tremor patients while lying and standing. The mesiofrontal hypometabolism correlated with increased body sway in posturography. This study confirms and further elucidates ponto-cerebello-thalamo-primary motor cortical activations underlying primary orthostatic tremor, which presented consistently in a group of patients. Compared to other tremor disorders one characteristic feature in orthostatic tremor seems to be the

Orthostatic effects on echocardiographic measures of ventricular function.

PubMed

Rowland, Thomas; Unnithan, Viswanath; Barker, Piers; Guerra, Miriam; Roche, Denise; Lindley, Martin

2012-05-01

Orthostatic-induced alterations in Doppler echocardiographic measures of ventricular function have not been well-defined. Identifying such changes may provide useful insights regarding the responses of these measures to variations in ventricular loading conditions. Standard assessment of mitral inflow velocity and tissue Doppler imaging (TDI) of left ventricular longitudinal myocardial velocities was performed on 14 young males (mean age 17.9 ± 0.7 years) in the supine position and then 5 minutes after assuming a sitting position with legs dependent. Upon sitting, average values of stroke volume and cardiac output fell by 28% and 18%, respectively, while heart rate increased from 64 ± 10 to 73 ± 12 beats/min (+14%) and calculated systemic vascular resistance rose from 12.9 ± 2.2 to 16.4 ± 3.1 units (+27%). Mitral E peak velocity declined from 87 ± 16 to 64 ± 16 cm/sec, and average TDI-E' and TDI-S both decreased (by -44% and -20%, respectively). When adjusted for orthostatic decreases in left ventricular end-diastolic volume, the mean decrease in TDI-E' was reduced to -29 (P < 0.01), but no significant decline was observed in adjusted TDI-S. Average E/E' rose with sitting by 40% (P = 0.02). These findings suggest that (a) decreases in TDI measures when assuming the upright position reflect the reduction of left ventricular size; (b) orthostatic fall in TDI-E' is also related to smaller ventricular size but, in addition, to a nonspecified reduction in ventricular relaxation; and (c) values of E/E' do not reflect alterations in ventricular preload, which occur during an orthostatic challenge. © 2012, Wiley Periodicals, Inc.

Orthostatic hypertension as a risk factor for age-related macular degeneration: Evidence from the Irish longitudinal study on ageing.

PubMed

Bhuachalla, Bláithín Ní; McGarrigle, Christine A; O'Leary, Neil; Akuffo, Kwadwo Owusu; Peto, Tunde; Beatty, Stephen; Kenny, Rose Anne

2018-06-01

Age related macular degeneration (AMD) is a leading cause of irreversible visual loss in developed countries. It is associated with vascular risk factors including hypertension. Dysregulated blood pressure (BP) behaviour including orthostatic hypertension (OHTN), hypotension (OH) and BP variability (BPV) are associated with end-organ damage, particularly in the brain. We investigated if abnormal orthostatic BP (OBP) was a risk factor for AMD, for which a vascular aetiology is implicated. A nationally representative, cross-sectional study was carried out 2009/2010 in The Irish Longitudinal Study on Ageing (TILDA). Beat-to-beat BP data, measured by digital photoplethysmography during active stand, was used to characterise OBP behaviour in the 30-110 s after standing. OH, OHTN, BPV and normal stabilisation recovery phenotypes were defined. AMD was identified following masked grading of 45° monoscopic colour retinal photographs, which were centred on the macula and taken with a NIDEK AFC-210 non-mydriatic auto-fundus camera. The relationship between OBP recovery phenotypes and AMD in 3750 adults aged ≥50 years was investigated using multivariate logistic regression models, adjusted for traditional AMD risk factors. From 30 to 110 s post active stand, systolic and diastolic OHTN was associated with increased odds of AMD after adjustment for demographics, health behaviours including smoking, family history of AMD, self-report (SR) diabetes, SR cataracts, objective hypertension and prescribed antihypertensives. No evidence of heterogeneity of OHTN effect was found between those who were hypertensive to those who were normotensive. This study provides evidence that OHTN may be an independent cardiovascular risk factor for AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

An assessment of fatigue in patients with postural orthostatic tachycardia syndrome.

PubMed

Wise, Shelby; Ross, Amanda; Brown, Abigail; Evans, Meredyth; Jason, Leonard

2017-05-01

Individuals with postural orthostatic tachycardia syndrome share many symptoms with those who have chronic fatigue syndrome; one of which is severe fatigue. Previous literature found that those with chronic fatigue syndrome experience many forms of fatigue. The goal of this study was to investigate whether individuals with postural orthostatic tachycardia syndrome also experience multidimensional fatigue and whether these individuals can be clustered into subgroups based on the types of fatigue they endorse. A convenience sample of 138 participants (aged 14-29) with postural orthostatic tachycardia syndrome completed questionnaires that assessed fatigue, brain fog symptom severity, activities that improve brain fog, and brain fog-related disability. An exploratory factor analysis was conducted on the Fatigue Types Questionnaire, and a three-factor solution was produced. Factor scores were then used to cluster the patients into groups using a TwoStep cluster analysis. This resulted in two clusters, a high severity group and a low severity group. The clusters were then compared on a number of items related to symptom expression. Individuals within the more severe cluster had significantly more brain fog at the beginning and end of the survey when compared to cluster two. Those in the more severe cluster also described more activity impairment as well as more frequent, more severe, and more debilitation from postural orthostatic tachycardia syndrome and brain fog. The findings of the factor analysis suggest that patients with postural orthostatic tachycardia syndrome experience fatigue as a multidimensional construct and they also can be subgrouped based on symptom severity.

Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team

NASA Technical Reports Server (NTRS)

Robertson, D.; Shannon, J. R.; Biaggioni, I.; Ertl, A. C.; Diedrich, A.; Carson, R.; Furlan, R.; Jacob, G.; Jordan, J.

2000-01-01

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.

Stroke Volume During Orthostatic Challenge: Comparison of Two Non-Invasive Methods

DTIC Science & Technology

2005-10-01

transition in posture from supine to HUT, a rapid me- chanical redistribution of blood from the central circu- lation toward the lower extremities...resting 12-lead ECG and clinical orthostatic exam ( supine /seated/ standing consecutive BP mea- surements) were obtained on each of the potential sub...during an orthostatic challenge has been reported elsewhere (4). Subjects maintained a supine posture for 30 min prior to the start of data collection

Drug effects on orthostatic intolerance induced by bedrest

NASA Technical Reports Server (NTRS)

Vernikos, J.; Dallman, M. F.; Van Loon, G.; Keil, L. C.

1991-01-01

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

Sympathoinhibition and hypotension in carotid sinus hypersensitivity

NASA Technical Reports Server (NTRS)

Smith, M. L.; Ellenbogen, K. A.; Eckberg, D. L.

1992-01-01

Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

Stressful life events and orthostatic blood pressure recovery in older adults.

PubMed

Feeney, Joanne; Dooley, Cara; Finucane, Ciarán; Kenny, Rose Anne

2015-07-01

The majority of the literature on stress and blood pressure (BP) concerns the increased risk of cardiovascular morbidity and mortality from high BP. Because the sympathetic nervous system is critical to the maintenance of orthostatic BP, it was hypothesized that older adults who have experienced more stressful life events (SLEs) would be more likely to show impaired recovery of BP in response to orthostatic stress. A total of 3,765 participants (Mage = 61.6 years, SD = 8.2; 54% female) from the first wave of The Irish Longitudinal Study on Ageing (TILDA) were included in the current analysis. Exposure to lifetime SLEs was ascertained by self-completion questionnaire, and beat-to-beat orthostatic BP measurement was carried out. Individuals who failed to recover at least 95% of their baseline BP by 60 s post stand were characterized as having impaired orthostatic BP recovery. An independent, dose-response relationship between the number of SLEs reported and the odds of impaired systolic BP recovery was observed after adjustment for covariates (1 event: odds ratio [OR] = 1.19, 95% confidence interval [CI] [0.98, 1.45], p = .078; 2 events: OR = 1.33, 95% CI [1.03, 1.73], p = .031; 3 or more events: OR = 1.56, 95% CI [1.12, 1.73], p = .009). This relationship was not evident for diastolic BP recovery. The reporting of a higher number of SLEs is associated with greater risk of impaired systolic BP recovery from orthostatic stress. Potential clinical implications include an increased risk of cerebral hypoperfusion, which predisposes older adults to falls, faints, and changes in cognitive status. (c) 2015 APA, all rights reserved.

Aerobic capacity, orthostatic tolerance, and exercise perceptions at discharge from inpatient spinal cord injury rehabilitation.

PubMed

Pelletier, Chelsea A; Jones, Graham; Latimer-Cheung, Amy E; Warburton, Darren E; Hicks, Audrey L

2013-10-01

To describe physical capacity, autonomic function, and perceptions of exercise among adults with subacute spinal cord injury (SCI). Cross-sectional. Two inpatient SCI rehabilitation programs in Canada. Participants (N=41; mean age ± SD, 38.9 ± 13.7y) with tetraplegia (TP; n=19), high paraplegia (HP; n=8), or low paraplegia (LP; n=14) completing inpatient SCI rehabilitation (mean ± SD, 112.9 ± 52.5d postinjury). Not applicable. Peak exercise capacity was determined by an arm ergometry test. As a measure of autonomic function, orthostatic tolerance was assessed by a passive sit-up test. Self-efficacy for exercise postdischarge was evaluated by a questionnaire. There was a significant difference in peak oxygen consumption and heart rate between participants with TP (11.2 ± 3.4;mL·kg(-1)·min(-1) 113.9 ± 19.7 beats/min) and LP (17.1 ± 7.5 mL·kg(-1)·min(-1); 142.8 ± 22.7 beats/min). Peak power output was also significantly lower in the TP group (30.0 ± 6.9W) compared with the HP (55.5 ± 7.56W) and LP groups (62.5 ± 12.2W). Systolic blood pressure responses to the postural challenge varied significantly between groups (-3.0 ± 33.5 mmHg in TP, 17.8 ± 14.7 mmHg in HP, 21.6 ± 18.7 mmHg in LP). Orthostatic hypotension was most prevalent among participants with motor complete TP (73%). Results from the questionnaire revealed that although participants value exercise and see benefits to regular participation, they have low confidence in their abilities to perform the task of either aerobic or strengthening exercise. Exercise is well tolerated in adults with subacute SCI. Exercise interventions at this stage should focus on improving task-specific self-efficacy, and attention should be made to blood pressure regulation, particularly in individuals with motor complete TP. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

How do pediatric anesthesiologists define intraoperative hypotension?

PubMed

Nafiu, Olubukola O; Voepel-Lewis, Terri; Morris, Michelle; Chimbira, Wilson T; Malviya, Shobha; Reynolds, Paul I; Tremper, Kevin K

2009-11-01

Although blood pressure (BP) monitoring is a recommended standard of care by the ASA, and pediatric anesthesiologists routinely monitor the BP of their patients and when appropriate treat deviations from 'normal', there is no robust definition of hypotension in any of the pediatric anesthesia texts or journals. Consequently, what constitutes hypotension in pediatric anesthesia is currently unknown. We designed a questionnaire-based survey of pediatric anesthesiologists to determine the BP ranges and thresholds used to define intraoperative hypotension (IOH). Members of the Society of Pediatric Anesthesia (SPA) and the Association of Paediatric Anaesthetists (APA) of Great Britain and Ireland were contacted through e-mail to participate in this survey. We asked a few demographic questions and five questions about specific definitions of hypotension for different age groups of patients undergoing inguinal herniorraphy, a common pediatric surgical procedure. The overall response rate was 56% (483/860), of which 76% were SPA members. Majority of the respondents (72%) work in academic institutions, while 8.9% work in institutions with fewer than 1000 annual pediatric surgical caseload. About 76% of respondents indicated that a 20-30% reduction in baseline systolic blood pressure (SBP) indicates significant hypotension in children under anesthesia. Most responders (86.7%) indicated that they use mean arterial pressure or SBP (72%) to define IOH. The mean SBP values for hypotension quoted by SPA members was about 5-7% lower across all pediatric age groups compared to values quoted by APA members (P = 0.001 for all age groups). There is great variability in the BP parameters used and the threshold used for defining and treating IOH among pediatric anesthesiologists. The majority of respondents considered a 20-30% reduction from baseline in SBP as indicative of significant hypotension. Lack of a consensus definition for a common clinical condition like IOH could have

Orthostatic Responses to Anticholinesterase Inhibition in Persons with SCI

PubMed Central

Wecht, Jill M.; Cirnigliaro, Christopher M.; Azarelo, Frank; Bauman, William A.; Kirshblum, Steven C.

2015-01-01

Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine thereby increasing systemic blood pressure (BP). The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE). Ten individuals with SCI (C4–C7) were studied on 2 occasions: visit 1) NO-D and visit 2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 minutes at each angle and 45 minutes at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP & DBP) were monitored and symptoms of OI and AE recorded. Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p<0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials. These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI. PMID:25916633

Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis.

PubMed

Brock, Malcolm; Chung, Tae Hwan; Gaddam, Sathvika Reddy; Kathait, Anjaneya Singh; Ober, Cecily; Georgiades, Christos

2016-12-01

Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia. Primary hyperhidrosis is also thought to be the result of sympathetic dysregulation. We present the case of a patient treated with CT-guided, percutaneous T2 EtOH sympatholysis for craniofacial hyperhidrosis. The patient also suffered from postural orthostatic tachycardia syndrome for many years and was unresponsive to treatment. Immediately after sympatholysis, the patient experienced resolution of both craniofacial hyperhidrosis and postural orthostatic tachycardia syndrome.

Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brock, Malcolm, E-mail: mabrock@jhmni.edu; Chung, Tae Hwan, E-mail: Tchang7@jhmi.edu; Gaddam, Sathvika Reddy, E-mail: drsathvikareddy@yahoo.com

Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia. Primary hyperhidrosis is also thought to be the result of sympathetic dysregulation. We present the case of a patient treated with CT-guided, percutaneous T2 EtOH sympatholysis for craniofacial hyperhidrosis. The patient also suffered from postural orthostatic tachycardia syndrome for many years and was unresponsive to treatment. Immediately after sympatholysis, the patient experiencedmore » resolution of both craniofacial hyperhidrosis and postural orthostatic tachycardia syndrome.« less

The effects of in-flight treadmill exercise on postflight orthostatic tolerance

NASA Technical Reports Server (NTRS)

Siconolfi, Steven F.; Charles, John B.

1992-01-01

In-flight aerobic exercise is thought to decrease the deconditioning effects of microgravity. Two deconditioning characteristics are the decreases in aerobic capacity (maximum O2 uptake) and an increased cardiovascular response to orthostatic stress (supine to standing). Changes in both parameters were examined after Shuttle flights of 8 to 11 days in astronauts who performed no in-flight exercise, a lower than normal volume of exercise, and a near-normal volume of exercise. The exercise regimen was a traditional continuous protocol. Maximum O2 uptake was maintained in astronauts who completed a near-normal exercise volume of in-flight exercise. Cardiovascular responses to stand test were equivocal among the groups. The use of the traditional exercise regimen as a means to maintain adequate orthostatic responses produced equivocal responses. A different exercise prescription may be more effective in maintaining both exercise capacity and orthostatic tolerance.

The Effects of Liquid Cooling Garments on Post-Space Flight Orthostatic Intolerance

NASA Technical Reports Server (NTRS)

Billica, Roger; Kraft, Daniel

1997-01-01

Post space flight orthostatic intolerance among Space Shuttle crew members following exposure to extended periods of microgravity has been of significant concern to the safety of the shuttle program. Following the Challenger accident, flight crews were required to wear launch and entry suits (LES). It was noted that overall, there appeared to be a higher degree of orthostatic intolerance among the post-Challenger crews (approaching 30%). It was hypothesized that the increased heat load incurred when wearing the LES, contributed to an increased degree of orthostatic intolerance, possibly mediated through increased peripheral vasodilatation triggered by the heat load. The use of liquid cooling garments (LCG) beneath the launch and entry suits was gradually implemented among flight crews in an attempt to decrease heat load, increase crew comfort, and hopefully improve orthostatic tolerance during reentry and landing. The hypothesis that the use of the LCG during reentry and landing would decrease the degree of orthostasis has not been previously tested. Operational stand-tests were performed pre and post flight to assess crewmember's cardiovascular system's ability to respond to gravitational stress. Stand test and debrief information were collected and databased for 27 space shuttle missions. 63 crewpersons wearing the LCG, and 70 crewpersons not wearing the LCG were entered into the database for analysis. Of 17 crewmembers who exhibited pre-syncopal symptoms at the R+O analysis, 15 were not wearing the LCG. This corresponds to a 21% rate of postflight orthostatic intolerance among those without the LCG, and a 3% rate for those wearing LCG. There were differences in these individual's average post-flight maximal systolic blood pressure, and lower minimal Systolic Blood pressures in those without LCG. Though other factors, such as type of fluid loading, and exercise have improved concurrently with LCG introduction, from this data analysis, it appears that LCG usage

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

NASA Technical Reports Server (NTRS)

Novak, V.; Spies, J. M.; Novak, P.; McPhee, B. R.; Rummans, T. A.; Low, P. A.

1998-01-01

BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance.

PubMed

Novak, V; Spies, J M; Novak, P; McPhee, B R; Rummans, T A; Low, P A

1998-09-01

Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress

NASA Technical Reports Server (NTRS)

Zhang, R.; Zuckerman, J. H.; Pawelczyk, J. A.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

Natural History Study of Synucleinopathies

ClinicalTrials.gov

2018-01-23

Patients With Synucleinopathies; Neurogenic Orthostatic Hypotension; Pure Autonomic Failure; REM Sleep Behavior Disorder; Parkinson Disease; Dementia With Lewy Bodies; Multiple System Atrophy; Shy-Drager Disease

Lower-body negative-pressure exercise and bed-rest-mediated orthostatic intolerance

NASA Technical Reports Server (NTRS)

Schneider, Suzanne M.; Watenpaugh, Donald E.; Lee, Stuart M C.; Ertl, Andrew C.; Williams, W. Jon; Ballard, Richard E.; Hargens, Alan R.

2002-01-01

PURPOSE: Supine, moderate exercise is ineffective in maintaining orthostatic tolerance after bed rest (BR). Our purpose was to test the hypothesis that adding an orthostatic stress during exercise would maintain orthostatic function after BR. METHODS: Seven healthy men completed duplicate 15-d 6 degrees head-down tilt BR using a crossover design. During one BR, subjects did not exercise (CON). During another BR, subjects exercised for 40 min.d(-1) on a supine treadmill against 50-60 mm Hg LBNP (EX). Exercise training consisted of an interval exercise protocol of 2- to 3-min intervals alternating between 41 and 65% (.)VO(2max). Before and after BR, an LBNP tolerance test was performed in which the LBNP chamber was decompressed in 10-mm Hg stages every 3 min until presyncope. RESULTS: LBNP tolerance, as assessed by the cumulative stress index (CSI) decreased after BR in both the CON (830 +/- 144, pre-BR vs 524 +/- 56 mm Hg.min, post-BR) and the EX (949 +/- 118 pre-BR vs 560 +/- 44 mm Hg.min, post-BR) conditions. However, subtolerance (0 to -50 mm Hg LBNP) heart rates were lower and systolic blood pressures were better maintained after BR in the EX condition compared with CON. CONCLUSION: Moderate exercise performed against LBNP simulating an upright 1-g environment failed to protect orthostatic tolerance after 15 d of BR.

Presyncopal/Non-Presyncopal Outcomes of Post Spaceflight Stand Tests are Consistent from Flight to Flight

NASA Technical Reports Server (NTRS)

Martin, D. S.; Meck, J. V.

2004-01-01

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. Fifty astronauts 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 twenty-five of these astronauts, their first flight in this database was also their first time to fly into space. For the remaining 25, their first flight in this database was their second, third or fourth flight, as data were available. No subject became presyncopal during preflight testing. Of the 50 subjects, 45 (90%) had the same outcome on their first and second fligh ts of this study. Of 14 subjects on whom we had data from a third mission, 12 had the same stand test outcome on all three flights (86% same outcome across three flights). There was no correlation between flight duration and orthostatic tolerance (r = 0.39). 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.

Effect of fluid ingestion on orthostatic responses following acute exercise

NASA Technical Reports Server (NTRS)

Davis, J. E.; Fortney, S. M.

1997-01-01

Orthostatic tolerance is impaired following an acute bout of exercise. This study examined the effect of fluid ingestion following treadmill exercise in restoring the cardiovascular responses to an orthostatic stress. Five men (age, 29.6 +/- 3.4 yrs) were exposed to a graded lower body negative (LBNP) pressure protocol (0 to -50 mmHg) during euhydration without exercise (C), 20 minutes after exercise dehydration (D), 20 minutes after exercise and fluid ingestion (FI20), and 60 minutes after exercise and fluid ingestion (FI60). Fluid ingestion (mean +/- SE) consisted of water-ingestion equivalent to 50% of the body weight lost during exercise (520 +/- 15 ml). Exercise dehydration resulted in significantly higher heart rates (119 +/- 8 vs 82 +/- 7 bpm), lower systolic blood pressures (95 +/- 1.7 vs 108 +/- 2.3 mmHg), a smaller increase in leg circumference (3.7 +/- 4 vs 6.9 +/- 1.0 mm), and an attenuated increase in total peripheral resistance (2.58 +/- 1.2 vs 4.28 +/- 0.9 mmHg/L/min) at -50 mmHg LBNP compared to the C condition. Fluid ingestion (both 20 and 60), partially restored the heart rate, systolic blood pressure, and total peripheral resistance responses to LBNP, but did not influence the change in leg circumference during LBNP (4 +/- 0.3 for R20 and 2.8 +/- 0.4 mm for R60). These data illustrate the effectiveness of fluid ingestion on improving orthostatic responses following exercise, and suggest that dehydration is a contributing factor to orthostatic intolerance following exercise.

Errata Corrige. Orthostatic Reactivity in Patients with Ischemic Stroke in the Chronic Period. http://dx.doi.org/10.3889/oamjms.2015.090.

PubMed

Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Grigorova-Petrova, Kristin; Dimitrova, Antoaneta

2015-09-15

This study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on orthostatic reactivity in patients with ischemic stroke in the chronic period (ISChP). An active orthostatic test is used for the evaluation of the orthostatic reactions. The arterial blood pressure and heart rate were defined in the 10 minutes of supine position, before and after 1, 5 and 10 minutes of active upright position. The orthostatic autoregulation is evaluated four times - at the beginning of the study, on the 10th day, on the 1st month and three months after the start of the KT. The classification by Thulesius was used to separate the patients into two groups depending on the type of their orthostatic reactivity. At the beginning of the study of infringements symptomatic type orthostatic reactivity (SOR) was observed in 24 patients and hypertensive type orthostatic reactivity (HOR) was observed in the remaining 32 patients. Once applied SKTM establish improvement of orthostatic autoregulation for the groups SOR and HOR at the 10th day and the 1st month with a level of significance p <0.05. The applied specialized kinesitherapeutic methodology continued later as an adapted exercise program at home, has significantly improved the orthostatic reactivity in patients with orthostatic dysregulation due to the ISChP.

Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome.

PubMed

Ruzieh, Mohammed; Dasa, Osama; Pacenta, Ann; Karabin, Beverly; Grubb, Blair

Postural orthostatic tachycardia syndrome (POTS) is a constellation of signs and symptoms that occur when a patient is upright and relieved by recumbence. Currently, no drugs are labeled for the treatment for POTS. Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance. To appraise the effect of Droxidopa in a clinical setting in patients with POTS refractory to other forms of treatment. A retrospective study of patients with POTS at our Syncope and Autonomic Disorders Center. Three hundred fifty-two patients were screened, 54 of them were prescribed Droxidopa and found to be eligible to include in our study. Symptoms of orthostatic intolerance, side effects of therapy and response to treatment. Statistical analyses were done using SPSS software. Thirty-seven patients were included in data analysis. Patients who failed to follow up, didn't obtain Droxidopa due to insurance and cost concerns, had hypertensive response to therapy or had allergic reaction were excluded from data analysis. The most frequently reported symptom was dizziness in 91.9% of patients, followed by syncope and fatigue in 70.3% and 67.6% of patients, respectively. Symptoms of dizziness, syncope and fatigue were reported less after treatment; 75.7%, 51.4% and 40.5%, respectively. There was no statistically significant difference in standing or sitting blood pressure before and after treatment. Despite the improvement in some symptoms. Only 27% of patients reported improved quality of life after treatment. Of total, 40.5% of patients stopped the treatment either due to side effects or ineffectiveness. Droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS but has diminutive impact on quality of life and blood pressure. Further assessment in large clinical trials is needed to evaluate its efficacy.

Blood pressure and plasma renin activity as predictors of orthostatic intolerance

NASA Technical Reports Server (NTRS)

Harrison, M. H.; Kravik, S. E.; Geelen, G.; Keil, L.; Greenleaf, J. E.

1985-01-01

The effect of 3 h standing, followed by a period of head-up tilt (HUT) on physiological response (orthostatic tolerance, blood pressure and heart rate), as well as on plasma vasopressin (PVP) and renin activity (PRA) were studied in 13 dehydrated (to 2.4 pct loss of body weight) subjects. Seven subjects showed signs of orthostatic intolerance (INT), manifested by sweating, pallor, nausea and dizziness. Prior to these symptoms, the INT subjects exhibited lower systolic (SP) and pulse (PP) pressures, and an elevated PRA, compared to the tolerant (TOL) subjects. HUT has aggravated increases of RPA in the INT subjects and caused an increase, higher than in TOL subjects, in PVP, while rehydration has greatly attenuated the PVP response to the HUT and decreased the PRA response. It is concluded that dehydration, together with measurements of SP, PP and PRA, may serve as a means of predicting orthostatic intolerance and may provide a physiological model for studying the causes of intolerance.

Cognitive performance in hypotensive persons with spinal cord injury.

PubMed

Jegede, Adejoke B; Rosado-Rivera, Dwindally; Bauman, William A; Cardozo, Christopher P; Sano, Mary; Moyer, Jeremy M; Brooks, Monifa; Wecht, Jill Maria

2010-02-01

Due to sympathetic de-centralization, individuals with spinal cord injury (SCI), especially those with tetraplegia, often present with hypotension, worsened with upright posture. Several investigations in the non-SCI population have noted a relationship between chronic hypotension and deficits in memory, attention and processing speed and delayed reaction times. To determine cognitive function in persons with SCI who were normotensive or hypotensive over a 24-h observation period while maintaining their routine activities. Subjects included 20 individuals with chronic SCI (2-39 years), 13 with tetraplegia (C4-8) and 7 with paraplegia (T2-11). Individuals with hypotension were defined as having a mean 24-h systolic blood pressure (SBP) below 110 mmHg for males and 100 mmHg for females, and having spent >or=50% of the total time below these gender-specific thresholds. The cognitive battery used included assessment of memory (CVLT), attention and processing speed (Digit Span, Stroop word and color and Oral Trails A), language (COWAT) and executive function (Oral Trails B and Stroop color-word). Demographic parameters did not differ among the hypotensive and normotensive groups; the proportion of individuals with tetraplegia (82%) was higher in the hypotensive group. Memory was significantly impaired (P < 0.05) and there was a trend toward slowed attention and processing speed (P < 0.06) in the hypotensive compared to the normotensive group. These preliminary data suggest that chronic hypotension in persons with SCI is associated with deficits in memory and possibly attention and processing speed, as previously reported in the non-SCI population.

Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

NASA Technical Reports Server (NTRS)

Jacob, G.; Robertson, D.; Mosqueda-Garcia, R.; Ertl, A. C.; Robertson, R. M.; Biaggioni, I.

1997-01-01

PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

Autogenic-Feedback Training: A Potential Treatment for Orthostatic Intolerance in Aerospace Crews

NASA Technical Reports Server (NTRS)

Cowings, P. S.; Toscano, W. B.; Miller, N. E.; Pickering, T. G.; Shapiro, D.; Stevenson, J.; Maloney, S.; Knapp, J.

1994-01-01

Postflight orthostatic intolerance has been identified as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder that are both effective and practical. A considerable body of clinical research has demonstrated that people can be taught to increase their own blood pressure voluntarily, and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The current pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, autogenic-feedback training (AFT), three men and two women participated in four to nine training (15-30-minute) sessions. At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures, that the subjects made ranged between 20 and 50 mm Hg under both supine and 45 deg head-up tilt conditions. These findings indicate that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Furthermore, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.

[The use of the orthostatic test for determining the work capacity of convalescents].

PubMed

Reshetiuk, A L; Volkova, P S; Zemskaia, L I; Gdal', V A

1990-06-01

The course of responses to the orthostatic test is analyzed in convalescents with a history of different diseases. Diagnostic factors were singled out characteristic of different groups of diseases including values of the cardiovascular, neuromuscular systems of the body. On the basis of obtained data a decimal classification of the working capacity of convalescents was worked out by their reaction to orthostatic effects.

Delta space plot analysis of cardiovascular coupling in vasovagal syncope during orthostatic challenge.

PubMed

Reulecke, S; Charleston-Villalobos, S; Voss, A; Gonzalez-Camarena, R; Gaitan-Gonzalez, M; Gonzalez-Hermosillo, J; Hernandez-Pacheco, G; Aljama-Corrales, T

2016-08-01

In this work, a graphical method to study cardiovascular coupling, called delta space plot analysis (DSPA), was introduced. The graphical representation is susceptible to be parameterized in shape and orientation. The usefulness of this technique was studied on cardiovascular data from patients with vasovagal syncope (VVS) and from controls. The study included 15 female patients diagnosed with VVS and 11 age-matched healthy female subjects. All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 18 minutes of 70° orthostatic phase. The DSPA parameters were obtained at different times during the HUT test, i.e., at baseline, early (first 5 min) and late (10-15 min) orthostatic phases. In baseline there were no considerable differences between female controls and female patients. During the late orthostatic phase, parameters from DSPA showed highly significantly (p=0.000003) reduced cardiovascular coupling in patients. Findings indicated a loss of control on cardiovascular coupling in female patients susceptible to vasovagal syncope during orthostatic challenge. In addition, this study provided promising results for a new graphical method to investigate cardiovascular coupling.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.

PubMed

Clyman, Ronald I; Wickremasinghe, Andrea; Merritt, T Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M; Attridge, Joshua T; Swanson, Jonathan R; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J

2014-06-01

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32 weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0 μg/kg) stimulation test (performed before the ligation), and at 10-12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1 × dopamine [μg/kg/min] + 1 × dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P = .006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones

PubMed Central

Clyman, Ronald I.; Wickremasinghe, Andrea; Merritt, T. Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M.; Attridge, Joshua T.; Swanson, Jonathan R.; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J.

2014-01-01

Objective To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. Study design We performed a multicenter study of infants born at <32 weeks gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured three times: before and after a cosyntropin (1.0 microgram/kg) stimulation test (performed prior to the ligation), and at 10–12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified Inotrope Score (1 x dopamine (μg/kg/min) + 1 x dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their highest Inotrope Score was >15. Results Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low post-operative cortisol levels were not associated with the overall incidence of hypotension following ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the odds ratio for developing catecholamine-resistant hypotension was OR=36.6, CI=2.8–476, p=0.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not due to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Conclusion Infants with low cortisol concentrations following PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. PMID:24636853

Postural hypotension and the anti-gravity suit.

PubMed

Brook, W H

1994-10-01

An air force anti-gravity suit, as used by fighter pilots to prevent loss of consciousness, has been successfully employed to treat severe postural hypotension in a patient with Shy-Drager syndrome. The definition of postural hypotension is reviewed, and reference is made to the previous use of the anti-gravity suit in the treatment of this condition.

Autonomic Cardiovascular Control and Executive Function in Chronic Hypotension.

PubMed

Duschek, Stefan; Hoffmann, Alexandra; Reyes Del Paso, Gustavo A; Ettinger, Ulrich

2017-06-01

Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained. The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output. Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance.

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

NASA Technical Reports Server (NTRS)

Vaziri, N. D.; Purdy, R. E. (Principal Investigator)

2003-01-01

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.

Mechanisms of Orthostatic Intolerance During Real and Simulated Microgravity

NASA Technical Reports Server (NTRS)

1997-01-01

Session MP1 includes short reports on: (1) Orthostatic Tests after 42 Days of Simulated Weightlessness; (2) Effects of 12 Days Exposure to Simulated Microgravity on Central Circulatory Hemodynamics in the Rhesus Monkey; (3) Increased Sensitivity and Resetting of Baroflex Control of Exercise Heart Rate After Prolonged Bed-Rest; (4) Complex Cardiovascular Dynamics and Deconditioning During Head-down Bed Rest; (5) The Cardiovascular Effects of 6 Hours of Head-down Tilt Upon Athletes and Non-athletes; (6) Individual Susceptibility to Post-spaceflight Orthostatic Intolerance: Contributions of Gender-related and Microgravity-related Factors; (7) Cassiopee Mission 1996: Comparison of Cardiovascular Alteration after Short and Long-term Spaceflights; (8) Cerebral and Femoral Flow Response to LBNP during 6 Month MIR Spaceflights (93-95); and (9) Cerebrovascular Changes due to Spaceflight and Postflight Presyncope.

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Hemodynamic and neurohormonal responses to extreme orthostatic stress in physically fit young adults

NASA Astrophysics Data System (ADS)

Grasser, E. K.; Goswami, N.; Rössler, A.; Vrecko, K.; Hinghofer-Szalkay, H.

2009-04-01

Blood pressure stability may be jeopardized in astronauts experiencing orthostatic stress. There is disagreement about cardiovascular and endocrine stress responses that emerge when a critical (presyncopal) state is reached. We studied hemodynamic and neurohormonal changes as induced by an orthostatic stress paradigm (head-up tilt combined with lower body negative pressure) that leads to a syncopal endpoint. From supine control to presyncope, heart rate increased by 78% and thoracic impedance by 12%. There was a 49% fall in stroke volume index, 19% in mean arterial blood pressure, 14% in total peripheral resistance index and 11% in plasma volume. Plasma norepinephrine rose by 107, epinephrine by 491, plasma renin activity by 167, and cortisol by 25%. Hemodynamic and hormonal changes of clearly different magnitude emerge in presyncope as compared to supine rest. Additional studies are warranted to reveal the exact time course of orthostatic changes up to syncopal levels.

Mechanisms of Orthostatic Tolerance Improvement Following Artificial Gravity Exposure Differ Between Men and Women

NASA Technical Reports Server (NTRS)

Evans, J. M.; Stenger, M. B.; Ferguson, C. R.; Ribiero, L. C.; Zhang, Q.; Moore, F. B.; Serrador, J.; Smith, J. D.; Knapp, C. F.

2014-01-01

We recently determined that a short exposure to artificial gravity (AG) improved the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned subjects. We now seek to determine the mechanisms of that improvement in these hypovolemic men and women. Methods. We determined the orthostatic tolerance limit (OTL) of 9 men and 8 women following a 90 min exposure to AG compared to 90 min of head down bed rest (HDBR). In both cases (21 days apart), subjects were made hypovolemic (low salt diet plus 20 mg intravenous furosemide). Orthostatic tolerance was determined from a combination of head up tilt and increasing lower body negative pressure until presyncope. Mean values and correlations with OTL were determined for heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance (Finometer), cerebral artery blood velocity (DWL), partial pressure of carbon dioxide (Novametrics) and body segmental impedance (UFI THRIM) were measured during supine baseline, during OTL to presyncope and during supine recovery Results. Orthostatic tolerance of these hypovolemic subjects was significantly greater on the day of AG exposure than on the HDBR day. Regression of OTL on these variables identified significant relationships on the HDBR day that were not evident on the AG day: resting TPR correlated positively while resting cerebral flow correlated negatively with OTL. On both days, women's resting stroke volume correlated positively with orthostatic tolerance. Higher group mean values of stroke volume and cerebral artery flow and lower values of blood pressure, peripheral vascular and cerebrovascular resistance both at control and during OTL testing were observed on the AG day. Even though regression of OTL on resting stroke volume was significant only in women, presyncopal stroke volume reached the same level on each day of study for both men and women while the OTL test lasted 30% longer in men and 22% longer in women. Cerebral artery flow appeared to

Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus.

PubMed

Brinth, Louise S; Pors, Kirsten; Theibel, Ann C; Mehlsen, Jesper

2015-05-21

Infections with human papilloma virus (HPV) can result in cervical, oropharyngeal, anal, and penile cancer and vaccination programs have been launched in many countries as a preventive measure. We report the characteristics of a number of patients with a syndrome of orthostatic intolerance, headache, fatigue, cognitive dysfunction, and neuropathic pain starting in close relation to HPV vaccination. Patients were referred for orthostatic intolerance following HPV vaccination. Symptoms of autonomic dysfunction were quantified by standardised questionnaire. The diagnosis of postural orthostatic tachycardia syndrome (POTS) rested on finding a sustained heart rate increment of >30 min(-1) (>40 min(-1) in adolescents) or to levels >120 min(-1) during orthostatic challenge. 35 women aged 23.3 ± 7.1 years participated. Twenty-five had a high level of physical activity before vaccination and irregular periods were reported by all patients not on treatment with oral contraception. Serum bilirubin was below the lower detection limit in 17 patients. Twenty-one of the referred patients fulfilled the criteria for a diagnosis of POTS (60%, 95%CI 43-77%). All patients had orthostatic intolerance, 94% nausea, 82% chronic headache, 82% fatigue, 77% cognitive dysfunction, 72% segmental dystonia, 68% neuropathic pain. In a population referred for symptoms of orthostatic intolerance and other symptoms consistent with autonomic dysfunction that began in close temporal association with a quadrivalent HPV vaccination, we identified a 60% prevalence of POTS. Further work is urgently needed to elucidate the potential for a causal link between the vaccine and circulatory abnormalities and to establish targeted treatment options for the affected patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone.

PubMed

Freitas, J; Santos, R; Azevedo, E; Costa, O; Carvalho, M; de Freitas, A F

2000-10-01

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol beta-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.

Associations of Baroreflex Sensitivity, Heart Rate Variability, and Initial Orthostatic Hypotension with Prenatal and Recent Postnatal Methylmercury Exposure in the Seychelles Child Development Study at Age 19 Years

PubMed Central

Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W.; Davidson, Philip W.; Myers, Gary J.; Bovet, Pascal

2015-01-01

Background: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Methods: Subjects in theSeychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects’ hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Results: Prenatal MeHg exposures were similar in boys and girls (6.7 ± 4.3, 6.7 ± 3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2 ± 5.8 vs 7.9 ± 4.3 ng/g, p = 0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8 ± 7 ms/mm Hg, PNN50: 24.9 ± 6.8%, rMSSD: 68 ± 22, LF/HF: 0.61 ± 0.28) in both sexes. After standing, 51.4% of subjects had a

Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

PubMed

Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W; Davidson, Philip W; Myers, Gary J; Bovet, Pascal

2015-03-23

A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5

Identification of Hypotensive Emergency Department Patients with Cardiogenic Etiologies.

PubMed

Henning, Daniel J; Kearney, Kathleen E; Hall, Michael Kennedy; Mahr, Claudius; Shapiro, Nathan I; Nichol, Graham

2018-02-01

Identify predictors of cardiogenic etiology among emergency department (ED) patients with hypotension, and use these predictors to create a clinical tool to discern cardiogenic etiology of hypotension. This secondary analysis evaluated a prospective cohort of consecutive patients with hypotension in an urban, academic, tertiary care ED from November 2012 to September 2013. We included adults with hypotension, defined as a new vasopressor requirement, systolic blood pressure (SBP) < 90 mm Hg after at least 1 L of crystalloid or 2 units packed red blood cells, or SBP < 90 mm Hg and fluids withheld due to concern for fluid overload. The primary outcome was cardiogenic etiology, adjudicated by two physician chart review, with 25% paired chart review (kappa = 0.92). We used multivariable logistic regression to predict cardiogenic etiology, utilizing clinical data abstracted from the electronic medical record. We created a prediction score from significant covariates and calculated its test characteristics for cardiogenic hypotension. Of 700 patients with hypotension, 107 (15.3%, 95% CI: 12.6%-18.0%) had cardiogenic etiology. Independent predictors of cardiogenic etiology were shortness of breath (OR 4.1, 95% CI: 2.5-6.7), troponin > 0.1 ng/mL (37.5, 7.1-198.2), electrocardiographic ischemia (8.9, 4.0-19.8), history of heart failure (2.0, 1.1-3.3), and absence of fever (4.5, 2.3-8.7) (area under the curve [AUC] = 0.83). The prediction score created from these predictors yielded 78% sensitivity and 77% specificity for cardiogenic etiology (AUC = 0.827). Clinical predictors offer reasonable ED screening sensitivity for cardiogenic hypotension, while demonstrating sufficient specificity to facilitate early cardiac interventions.

Multiple system atrophy

MedlinePlus

... syndrome; Neurologic orthostatic hypotension; Shy-McGee-Drager syndrome; Parkinson plus syndrome; MSA-P; MSA-C ... ncbi.nlm.nih.gov/pubmed/25587949 . Jankovic J. Parkinson disease and other movement disorders. In: Daroff RB, ...

Autogenic-feedback training: A potential treatment for post-flight orthostatic intolerance in aerospace crews

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Toscano, William B.; Miller, Neil E.; Pickering, Thomas G.; Shapiro, David

1993-01-01

Postflight orthostatic intolerance was identified as a serious biomedical problem associated with long duration exposure to microgravity in space. High priority was given to the development of countermeasures for this disorder which are both effective and practical. A considerable body of clinical research demonstrated that people can be taught to increase their own blood pressure voluntarily and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The present pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), three men and two women participated in four to nine (15-30 training sessions). At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures that the subjects made, ranged between 20 and 5O mmHg under both supine and 45 deg head-up tilt conditions. These findings suggest that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Further, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.

A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

PubMed Central

Dage, R.C.

1979-01-01

1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

Effect of hydration on some orthostatic and haematological responses to head-up tilt

NASA Technical Reports Server (NTRS)

Harrison, M. H.; Hill, L. C.; Spaul, W. A.; Greenleaf, J. E.

1986-01-01

Experiments were undertaken to determine the effects of hydration status on: (1) orthostatic responses, and on (2) relative changes in intravascular volume and protein content, during 70 deg head-up tilt (HUT). Six men underwent 45 min of HUT, preceded by 45 min supine, first dehydrated, and again 105 min later after rehydration with water. Heart rate was consistently lower following rehydration (p less than 0.01), while supine diastolic pressure was higher (p less than 0.02). Systolic pressure fell during dehydrated HUT (p less than 0.01), but not during rehydrated HUT. Postural haemoconcentration, which was reduced after rehydration (p less than 0.001), was accompanied by a decrease in intravascular albumin content (p less than 0.05). Two subjects experienced severe presyncopal symptoms during dehydrated HUT, but not during rehydrated HUT. Thus, it appears that rehydration after fluid restriction improves orthostatic tolerance. Furthermore, extravascular hydration status may be more important than intravascular hydration status in determining orthostatic tolerance.

Prevalence of hypotension and its association with cognitive function among older adults.

PubMed

Momtaz, Yadollah Abolfathi; Hamid, Tengku Aizan; Haron, Sharifah Azizah; Bagat, Mohamad Fazdillah; Mohammadi, Fatemeh

2018-04-01

The negative effect of hypertension has overshadowed possible health problems associated with hypotension. The purposes of this study were to describe the prevalence of hypotension in older adults and to determine the association between hypotension and cognitive function, after adjusting for possible covariates. The data for the study consisting of 1067 community-dwelling older adults were obtained from a national survey entitled "Identifying Psychosocial and Identifying Economic Risk Factor of Cognitive Impairment among Elderly", conducted in Malaysia. The hypotension was considered as blood pressure <120/75 mm Hg, measuring by standard mercury manometer. Data analysis was performed using the SPSS Version 22.0. The mean age of the respondents was 68.27 (SD = 5.93). Mean score of cognitive function as measured by MMSE was 22.70 (SD = 4.95). The prevalence of hypotension was 29.3%. The prevalence of cognitive impairment for hypotension group was 25.6%. Results of multiple linear regression analysis revealed that hypotension is negatively associated with cognitive function (Beta = -0.11, p<.01), after adjusting for age, gender, education, marital status, employment status, diabetes, heart disease, stroke and gastritis. The study showing hypotension is significantly associated with decreased cognitive function in later life, implies more attention to low blood pressure in old age.

Caloric Restriction Decreases Orthostatic Tolerance Independently from 6° Head-Down Bedrest

PubMed Central

Florian, John P.; Baisch, Friedhelm J.; Heer, Martina; Pawelczyk, James A.

2015-01-01

Astronauts consume fewer calories during spaceflight and return to earth with an increased risk of orthostatic intolerance. Whether a caloric deficiency modifies orthostatic responses is not understood. Thus, we determined the effects of a hypocaloric diet (25% caloric restriction) during 6° head down bedrest (an analog of spaceflight) on autonomic neural control during lower body negative pressure (LBNP). Nine healthy young men completed a randomized crossover bedrest study, consisting of four (2 weeks each) interventions (normocaloric bedrest, normocaloric ambulatory, hypocaloric bedrest, hypocaloric ambulatory), each separated by 5 months. Muscle sympathetic nerve activity (MSNA) was recorded at baseline following normocaloric and hypocaloric interventions. Heart rate (HR) and arterial pressure were recorded before, during, and after 3 consecutive stages (7 min each) of LBNP (-15, -30, -45 mmHg). Caloric and posture effects during LBNP were compared using two-way ANOVA with repeated measures. There was a strong trend toward reduced basal MSNA following caloric restriction alone (normcaloric vs. hypocaloric: 22±3 vs. 14±4 burst/min, p = 0.06). Compared to the normocaloric ambulatory, both bedrest and caloric restriction were associated with lower systolic blood pressure during LBNP (p<0.01); however, HR responses were directionally opposite (i.e., increase with bedrest, decrease with caloric restriction). Survival analysis revealed a significant reduction in orthostatic tolerance following caloric restriction (normocaloric finishers: 12/16; hypocaloric finishers: 6/16; χ2, p = 0.03). Caloric restriction modifies autonomic responses to LBNP, which may decrease orthostatic tolerance after spaceflight. PMID:25915488

Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS)

MedlinePlus

... Professional Version Sleep Disorders Overview of Sleep Snoring Insomnia and Excessive Daytime Sleepiness (EDS) Circadian Rhythm Sleep ... pressure when a person stands (orthostatic hypotension), and insomnia. Benzodiazepines: These drugs (such as clonazepam ) cause drowsiness, ...

A Potential Treatment for Post-Flight Orthostatic Intolerance in Aero-Space Crews: Autogenic-Feedback Training

NASA Technical Reports Server (NTRS)

Cowings, P. S.; Toscano, W. B.; Miller, N. E.; Pickering, T. G.; Shapiro, D.

1994-01-01

Postflight orthostatic intolerance has been identified as a serious biomedical problem associated with long duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder which are both effective and practical. A considerable body of clinical research has demonstrated that people can be taught to increase their own blood pressure voluntarily and that this is an effective treatment for chronic Orthostatic intolerance in paralyzed patients. The present pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using in operant conditioning procedure, Autogenic-Feedback Training (AFT), three men and two women participated in four to nine (15-30 training sessions). At the end of training ranged between 20 and 50 mm Hg under both supine and 450 head-up tilt conditions. These findings suggest that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight Orthostatic intolerance. Further, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.

The periaqueductal grey area and the cardiovascular system.

PubMed

Green, A L; Wang, S; Owen, S L F; Aziz, T Z

2007-01-01

In this chapter, we report that blood pressure can be increased or decreased depending on whether an electrode is in ventral or dorsal PAG. We also describe that it is theoretically possible to treat orthostatic hypotension. These are exciting developments not only because they provide an example of direct translational research from animal research to humans but also because they highlight a potential for future clinical therapies. The control of essential hypertension without drugs is attractive because of the side effects of medication such as precipitation of heart failure [10]. Similarly, drug treatment of orthostatic hypotension cannot differentiate between the supine and standing positions and can therefore lead to nocturnal hypertension [22, 29]. A stimulator could be turned off at night or contain a mercury switch that reacts to posture.

Unique manifestations of catecholamine release in malignant pheochromocytoma: an experience within an inpatient palliative care unit.

PubMed

Coupe, Nicholas Anthony; Lacey, Judith; Sanderson, Christine

2012-05-01

Malignant pheochromocytoma is a rare disorder. We describe the case of a 41-year-old female with disseminated metastatic pheochromocytoma who was admitted for ongoing palliative and supportive care within an inpatient palliative care unit. Predominant symptoms included severe gastrointestinal pseudo-obstruction and orthostatic hypotension Pseudo-obstruction management included percutaneous enterogastric and percutaneous enterojejunostomy tubes for gastric decompression and delivery of nutrition, respectively. Debilitating symptoms of orthostatic hypotension were mitigated with judicious fluid balance and appropriate use of adrenergic blocking agents. The potential for metoclopramide to worsen symptoms also was a significant component of management. The case presents rare features of this unusual disease and is unique for its setting within the confines of a palliative care unit. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Preserved autonomic heart rate modulation in chronic renal failure patients in response to hemodialysis and orthostatism.

PubMed

Lerma, Claudia; González, Hortensia; Pérez-Grovas, Hector; José, Marco V; Infante, Oscar

2015-04-01

The aim of this work was to measure the impact of active orthostatism and hemodialysis (HD) upon heart rate variability (HRV) in chronic renal failure (CRF) patients before and after HD. Nineteen healthy subjects (age 27 ± 8 years old, 13 were female) and 19 unmedicated CRF patients with HD thrice per week (average HD vintage = 12 months, age 32 ± 9 years old, 11 were female) were included. Five-minute length HRV time series were obtained during supine position and orthostatism. Recordings from CRF patients were obtained before and after HD. Time domain and frequency domain HRV indexes were compared by analysis of variance. The correlation between each HRV index and change in sympathetic weighting induced by different maneuvers was tested by Kendall's Tau correlation. A p value <0.05 was considered statistically significant. HRV indexes which are associated with sympathetic activity increased in response to orthostatism in the healthy group, e.g., low-frequency to high-frequency (LF/HF) ratio, Ln (LF/HF) = -0.3 ± 0.9 versus 0.9 ± 0.9. CRF patients before HD had higher sympathetic weighting than healthy participants, even in supine position, Ln (LF/HF) = 0.6 ± 1.0, but such a difference was accentuated during orthostatism, Ln (LF/HF) = 1.5 ± 1.0, and after HD: Ln (LF/HF) = 0.8 ± 1.3 (supine position) and 2.5 ± 2.1 (orthostatism). All HRV indexes were associated with increments in sympathetic weighting between maneuvers (Kendall's correlations absolute values ≥ 0.24). Unmedicated young CRF patients treated with hemodynamically stable maintenance HD showed preserved capacity of autonomic response (with gradual sympathetic increases) induced by cardiovascular challenges such as orthostatism and HD.

Inter-Relations of Orthostatic Blood Pressure Change, Aortic Stiffness, and Brain Structure and Function in Young Adults.

PubMed

Cooper, Leroy L; Himali, Jayandra J; Torjesen, Alyssa; Tsao, Connie W; Beiser, Alexa; Hamburg, Naomi M; DeCarli, Charles; Vasan, Ramachandran S; Seshadri, Sudha; Pase, Matthew P; Mitchell, Gary F

2017-08-17

Relations of orthostatic change in blood pressure with brain structure and function have not been studied thoroughly, particularly in younger, healthier individuals. Elucidation of factors that contribute to early changes in brain integrity may lead to development of interventions that delay or prevent cognitive impairment. In a sample of the Framingham Heart Study Third Generation (N=2119; 53% women; mean age±SD, 47±8 years), we assessed orthostatic change in mean arterial pressure (MAP), aortic stiffness (carotid-femoral pulse wave velocity), neuropsychological function, and markers of subclinical brain injury on magnetic resonance imaging. Multivariable regression analyses were used to assess relations between orthostatic change in MAP and brain structural and neuropsychological outcomes. Greater orthostatic increase in MAP on standing was related to better Trails B-A performance among participants aged <49 years (β±SE, 0.062±0.029; P =0.031) and among participants with carotid-femoral pulse wave velocity <6.9 m/s (β±SE, 0.063±0.026; P =0.016). This relation was not significant among participants who were older or had stiffer aortas. Conversely, greater orthostatic increase in MAP was related to larger total brain volume among older participants (β±SE, 0.065±0.029; P =0.023) and among participants with carotid-femoral pulse wave velocity ≥6.9 m/s (β±SE, 0.078±0.031; P =0.011). Blunted orthostatic increase in MAP was associated with smaller brain volume among participants who were older or had stiffer aortas and with poorer executive function among persons who were younger or who had more-elastic aortas. Our findings suggest that the brain is sensitive to orthostatic change in MAP, with results dependent on age and aortic stiffness. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Tolerance of beta blocked hypertensives during orthostatic and altitude stress.

DOT National Transportation Integrated Search

1992-04-01

To evaluate the effects of orthostatic, altitude, and pharmacologic stresses upon civil aviation-specific performance, a double-blind, randomized, crossover trial of atenolol, 100mg, was designed and executed. Hypertensive males are females qualifyin...

Alterations in muscular performance and orthostatic tolerance during Ramadan.

PubMed

Bigard, A X; Boussif, M; Chalabi, H; Guezennec, C Y

1998-04-01

During Ramadan, physiological changes are expected to result from both long-term dietary restriction and partial sleep loss. We speculated that Ramadan fasting has deleterious effects on muscle performances and on orthostatic tolerance. There were 11 senior fighter pilots tested on three occasions during the first week of Ramadan (Beg-R), during the fourth week (End-R) and during a control period, 2 mo after Ramadan (C). Each test session consisted of an assessment of the strength and endurance performances of the knee extensors and elbow flexors and of an analysis of the HR and BP responses to the orthostatic stress imposed by a 80 degrees head-up tilt. Body weight decreased by 2.7% at End-R in comparison with C period (p < 0.01). Maximum isometric strength (MVC) of elbow flexor muscles decreased immediately (by 10-12%; p < 0.05). Muscular endurance at both 35 and 70% MVC were lower at End-R in comparison with C period (-28%, -22%, respectively; p < 0.05). The head-up tilt test at End-R was accompanied by a higher increase in heart response than during orthostasis during C and Beg-R periods, and by a decrease in pulse pressures (p < 0.001). These alterations in responses to the head-up tilt were associated with a fall by about 7% in plasma volume. These data demonstrate that Ramadan fasting leads to an impairment in muscular performances and to a decrease in orthostatic tolerance. Further studies are needed to verify the impact of these changes on +Gz tolerance.

Development of a model to assess orthostatic responses

NASA Technical Reports Server (NTRS)

Rubin, Marilyn

1993-01-01

A major change for crewmembers during weightlessness in microgravity is the redistribution of body fluids from the legs into the abdomen, thorax, and head. The fluids continue to be sequestered in these areas throughout the flight. Upon reentry into gravity on landing, these same body fluids are displaced again to their normal locations, however, not without hazardous incidence to the crewmembers. The problem remains that upon landing, crewmembers are subject to orthostasis, that is, the blood flowing into the legs reduces the blood supply to the brain and may result in the crewmember fainting. The purpose of this study was to develop a model of testing orthostatic responses of blood pressure regulating mechanisms of the cardiovascular system, when challenged, to maintain blood pressure to the brain. To accomplish this, subjects' responses were assessed as they proceeded from the supine position of progressive head-up tilt positions of 30 deg, 60 deg, and 90 deg angles. A convenience sample consisted of 21 subjects, females (N=11) and males (N=10), selected from a list of potential subjects available through the NASA subject screening office. The methodology included all non-invasive measurements of blood pressure, heart rate, echocardiograms, cardiac output, cardiac stroke volume, fluid shifts in the thorax, ventricular ejection and velocity times, and skin blood perfusion. The Fischer statistical analysis was done of all data with the significance level at .05. Significant differences were demonstrated in many instances of changes of posture for all variables. Based on the significance of the findings of this study, this model for assessing orthostatic responses does provide an adequate challenge to the blood pressure regulatory systems. While individuals may use different adaptations to incremental changes in gravity, the subjects, in aggregate, demonstrated significant adaptive cardiovascular changes to orthostatic challenges which were presented to them.

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience.

PubMed

Kanjwal, Khalil; Karabin, Beverly; Sheikh, Mujeeb; Elmer, Lawrence; Kanjwal, Yousuf; Saeed, Bilal; Grubb, Blair P

2011-06-01

The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients. This retrospective study included an extensive review of electronic charts and data collection in regards to patient demographics, orthostatic parameters, side-effect profile, subjective response to therapy, as well as laboratory studies recorded at each follow-up visit to our institution's Syncope and Autonomic Disorders Center. The response to pyridostigmine therapy was considered successful if patient had both symptom relief in addition to an objective response in orthostatic hemodynamic parameters (heart rate [HR] and blood pressure). Three hundred patients with POTS were screened for evaluation in this study. Of these 300, 203 patients with POTS who received pyridostigmine therapy were reviewed. Of these 203 patients, 168 were able to tolerate the medication after careful dose titration. The mean follow-up duration in this group of patients was 12 ± 3 (9-15) months. Pyridostigmine improved symptoms of orthostatic intolerance in 88 of 203 (43%) of total patients or 88 of 172 (51%) who were able to tolerate the drug. The symptoms that improved the most included fatigue (55%), palpitations (60%), presyncope (60%), and syncope (48%). Symptom reduction correlated with a statistically significant improvement in upright HR and diastolic blood pressure after treatment with pyridostigmine as compared to their baseline hemodynamic parameters (standing HR 94 ± 19 vs 82 ± 16, P < 0.003, standing diastolic blood pressure 71 ± 11 vs 74 ± 12, P < 0.02). Gastrointestinal problems were the most common adverse effects (n = 39, 19%) reported. The overall efficacy of pyridostigmine in our study was seen in 42% of total patients or

[The effects of Cardiodoron on cardio-respiratory coordination--a literature review].

PubMed

Cysarz, D; Heckmann, C; Kümmell, H C

2002-10-01

In healthy subjects self-regulation of the organism establishes the order of rhythmical functions. This self-regulation is altered in patients suffering from idiopathic orthostatic syndrome resulting from disturbances of functional aspects only. Thus the cardio-respiratory coordination, which may serve as the representative of the order of rhythmical functions, is modified. In the case of idiopathic orthostatic syndrome the anthroposophic medicine offers the medicament Cardiodoron(r). Does it stimulate self-regulation in order to normalise the cardio-respiratory coordination? This claim is analysed by a systematic review of the literature. Only those publications were considered where the cardio-respiratory coordination was analysed in studies with patients or healthy subjects. The methods of the studies with patients and healthy subjects vary strongly. Nevertheless, a normalisation of the cardio-respiratory coordination could be found in studies with patients suffering from idiopathic orthostatic syndrome as well as in studies with healthy subjects. The studies show that the use of the medicament results in a normalisation of the cardiorespiratory coordination. By stimulating the self-regulation the medicament leads to an improvement of the order of rhythmical functions in the human organism. Copyright 2002 S. Karger GmbH, Freiburg

Extrusion of the medial meniscus in knee osteoarthritis assessed with a rotating clino-orthostatic permanent-magnet MRI scanner.

PubMed

Paparo, Francesco; Revelli, Matteo; Piccazzo, Riccardo; Astengo, Davide; Camellino, Dario; Puntoni, Matteo; Muda, Alessandro; Rollandi, Gian Andrea; Garlaschi, Giacomo; Cimmino, Marco Amedeo

2015-04-01

The objectives of this study were to assess the influence of weight-bearing on tibiofemoral osteoarthritis, including medial meniscal extrusion, by using a low-field (0.25 T) rotating clino-orthostatic permanent-magnet magnetic resonance (MR) scanner, and to analyse correlations of medial meniscal extrusion with the patient's Kellgren-Lawrence score, body mass index, and all the osteoarthritis features of the WORMS scoring system. Twenty-six patients (69.2% women and 30.8% men; mean age 67 ± 9.7 years) with medial tibiofemoral knee osteoarthritis were prospectively enrolled and MR sequences were acquired in both clino- and orthostatic position. MR images were assessed by two independent radiologists, according to the WORMS scale. Medial meniscal extrusion was measured and its clino-orthostatic difference (∆MME) was calculated. Intra- and inter-observer agreement of the WORMS Global Score readings was high by Cohen's K test (>0.81). No significant clino-orthostatic changes in the scoring parameters of the medial tibiofemoral joint were shown by Wilcoxon's test. Medial meniscal extrusion measured on orthostatic images was significantly higher than that measured in clinostatic position (p < 0.0001). At univariate analysis, the Kellgren-Lawrence score, WORMS Global Score, cartilage loss, meniscal damage, and osteophytes were significantly correlated to ∆MME (p < 0.005). Using a multiple regression model, tibiofemoral cartilage loss was found to correlate independently with ∆MME (p = 0.0499). Medial meniscal extrusion, evaluated with an open-configuration, rotating MR scanner, increased from the clinostatic to the orthostatic position. ∆MME, a new meniscal parameter, correlated with several important features of medial tibiofemoral osteoarthritis.

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetics and molecular biology of hypotension

NASA Technical Reports Server (NTRS)

Robertson, D.

1994-01-01

Major strides in the molecular biology of essential hypertension are currently underway. This has tended to obscure the fact that a number of inherited disorders associated with low blood pressure exist and that these diseases may have milder and underrecognized phenotypes that contribute importantly to blood pressure variation in the general population. This review highlights some of the gene products that, if abnormal, could cause hypotension in some individuals. Diseases due to abnormalities in the catecholamine enzymes are discussed in detail. It is likely that genetic abnormalities with hypotensive phenotypes will be as interesting and diverse as those that give rise to hypertensive disorders.

The Association Between Mild Intraoperative Hypotension and Stroke in General Surgery Patients.

PubMed

Hsieh, Jason K; Dalton, Jarrod E; Yang, Dongsheng; Farag, Ehab S; Sessler, Daniel I; Kurz, Andrea M

2016-10-01

Intraoperative hypotension may contribute to perioperative strokes. We therefore tested the hypothesis that intraoperative hypotension is associated with perioperative stroke. After institutional review board approval for this case-control study, we identified patients who had nonneurological, noncardiac, and noncarotid surgery under general anesthesia at the Cleveland Clinic between 2005 and 2011 and experienced a postoperative stroke. Control patients not experiencing postoperative stroke were matched in a 4-to-1 ratio using propensity scores and restriction to the same procedure type as stroke patients. The association between intraoperative hypotension, measured as time-integrated area under a mean arterial pressure (MAP) of 70 mm Hg, and postoperative stroke was assessed using zero-inflated negative binomial regression. Among 106 337 patients meeting inclusion criteria, we identified 120 who had confirmed postoperative stroke events based on manual chart review. Four-to-one propensity matching yielded a final matched sample of 104 stroke cases and 398 controls. There was no association between stroke and intraoperative hypotension. Stroke patients were not more likely than controls to have been hypotensive (odds ratio, 0.49 [0.18-1.38]), and among patients with intraoperative hypotension, stroke patients did not experience a greater degree of hypotension than controls (ratio of geometric means, 1.07 [0.76-1.53]). In our propensity score-matched case-control study, we did not find an association between intraoperative hypotension, defined as MAP < 70 mm Hg, and postoperative stroke.

Resistance exercise training and the orthostatic response

NASA Technical Reports Server (NTRS)

McCarthy, J. P.; Bamman, M. M.; Yelle, J. M.; LeBlanc, A. D.; Rowe, R. M.; Greenisen, M. C.; Lee, S. M.; Spector, E. R.; Fortney, S. M.

1997-01-01

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P < 0.05) by 4-14%, lean body mass increased (P = 0.00) by 2.0 (0.5) kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (125I and 51Cr) and red cell mass were increased (P < 0.02) by 2.8% and 3.9%, respectively. These findings indicate that intense resistance exercise increases blood volume but does not consistently improve orthostatic tolerance.

Are Compression Stockings an Effective Treatment for Orthostatic Presyncope?

PubMed Central

Protheroe, Clare Louise; Dikareva, Anastasia; Menon, Carlo; Claydon, Victoria Elizabeth

2011-01-01

Background Syncope, or fainting, affects approximately 6.2% of the population, and is associated with significant comorbidity. Many syncopal events occur secondary to excessive venous pooling and capillary filtration in the lower limbs when upright. As such, a common approach to the management of syncope is the use of compression stockings. However, research confirming their efficacy is lacking. We aimed to investigate the effect of graded calf compression stockings on orthostatic tolerance. Methodology/Principal Findings We evaluated orthostatic tolerance (OT) and haemodynamic control in 15 healthy volunteers wearing graded calf compression stockings compared to two placebo stockings in a randomized, cross-over, double-blind fashion. OT (time to presyncope, min) was determined using combined head-upright tilting and lower body negative pressure applied until presyncope. Throughout testing we continuously monitored beat-to-beat blood pressures, heart rate, stroke volume and cardiac output (finger plethysmography), cerebral and forearm blood flow velocities (Doppler ultrasound) and breath-by-breath end tidal gases. There were no significant differences in OT between compression stocking (26.0±2.3 min) and calf (29.3±2.4 min) or ankle (27.6±3.1 min) placebo conditions. Cardiovascular, cerebral and respiratory responses were similar in all conditions. The efficacy of compression stockings was related to anthropometric parameters, and could be predicted by a model based on the subject's calf circumference and shoe size (r = 0.780, p = 0.004). Conclusions/Significance These data question the use of calf compression stockings for orthostatic intolerance and highlight the need for individualised therapy accounting for anthropometric variables when considering treatment with compression stockings. PMID:22194814

Contrasting effects of vasodilators on blood pressure and sodium balance in the hypertension of autonomic failure

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Pohar, B.; Paranjape, S. Y.; Robertson, D.; Robertson, R. M.; Biaggioni, I.

1999-01-01

Supine hypertension, which is very common in patients with autonomic failure, limits the use of pressor agents and induces nighttime natriuresis. In 13 patients with severe orthostatic hypotension due to autonomic failure (7 women, 6 men, 72 +/- 3 yr) and supine hypertension, the effect of 30 mg nifedipine (n = 10) and 0.025 to 0.2 mg/h nitroglycerin patch (n = 11) on supine BP, renal sodium handling, and orthostatic tolerance was determined. Medications were given at 8 p.m.; patients stood up at 8 a.m. Nitroglycerin was removed at 6 a.m. Compared with placebo, nifedipine and nitroglycerin decreased systolic BP during the night by a maximum of 37 +/- 9 and 36 +/- 10 mmHg, respectively (P < 0.01). At 8 a.m., supine systolic BP was 23 +/- 7 mmHg lower with nifedipine than with placebo (P < 0.05), but was similar with nitroglycerin and placebo. Sodium excretion during the night was not reduced with nitroglycerin (0.13 +/- 0.02 mmol/mg creatinine [Cr] versus 0.15 +/- 0.03 mmol/mg Cr with placebo), but it was increased with nifedipine (0.35 +/- 0.06 mmol/mg Cr versus 0.13 +/- 0.02 mmol/mg Cr with placebo, P < 0.05). Nifedipine but not nitroglycerin worsened orthostatic hypotension in the morning. It is concluded that nifedipine and transdermal nitroglycerin are effective in controlling supine hypertension in patients with autonomic failure. However, nifedipine has a prolonged depressor effect and worsens orthostatic hypotension in the morning. The decrease in pressure natriuresis that would be expected with the substantial decrease in BP obtained with nitroglycerin and nifedipine may be offset by a direct effect of both drugs on renal sodium handling.

High Intensity Exercise Countermeasures does not Prevent Orthostatic Intolerance Following Prolonged Bed Rest

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Ploutz-Snyder, Lori L.; Lee, Stuart M. C.

2014-01-01

Approximately 20% of Space Shuttle astronauts became presyncopal during operational stand and 80deg head-up tilt tests, and the prevalence of orthostatic intolerance increases after longer missions. Greater than 60% of the US astronauts participating in Mir and early International Space Station missions experienced presyncope during post-flight tilt tests, perhaps related to limitations of the exercise hardware that prevented high intensity exercise training until later ISS missions. The objective of this study was to determine whether an intense resistive and aerobic exercise countermeasure program designed to prevent cardiovascular and musculoskeletal deconditioning during 70 d of bed rest (BR), a space flight analog, would protect against post-BR orthostatic intolerance. METHODS Twenty-six subjects were randomly assigned to one of three groups: non-exercise controls (n=11) or one of two exercise groups (ExA, n=8; ExB, n=7). Both ExA and ExB groups performed the same resistive and aerobic exercise countermeasures during BR, but one exercise group received testosterone supplementation while the other received a placebo during BR in a double-blinded fashion. On 3 d/wk, subjects performed lower body resistive exercise and 30 min of continuous aerobic exercise (=75% max heart rate). On the other 3 d/wk, subjects performed only highintensity, interval-style aerobic exercise. Orthostatic intolerance was assessed using a 15-min 80? head-up tilt test performed 2 d (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using carbon monoxide rebreathing on BR-3 and before rising on the first recovery day (BR+0). The code for the exercise groups has not been broken, and results are reported here without group identification. RESULTS Only one subject became presyncopal during tilt testing on BR-2, but 7 of 11 (63%) controls, 3 of 8 (38%) ExA, and 4 of 7 (57%) ExB subjects were presyncopal on BR70. Survival analysis of post-BR tilt tests revealed no

Nimodipine-induced hypotension but not nitroglycerin-induced hypotension preserves long- and short-term memory in adult mice.

PubMed

Haile, Michael; Galoyan, Samuel; Li, Yong-Sheng; Cohen, Barry H; Quartermain, David; Blanck, Thomas; Bekker, Alex

2012-05-01

Acute hypotension may be implicated in cognitive dysfunction. L-type calcium channel blockers in the setting of hypoxia are protective of learning and memory. We tested the hypothesis that hypotension induced by nimodipine (NIMO) and nicardipine (NICA) would be protective of long- and short-term memory compared to hypotension induced by nitroglycerin (NTG). Forty Swiss-Webster mice (30 to 35 g, 6 to 8 weeks) were randomized into 4 groups for i.p. injection immediately after passive avoidance (PA) learning on day 0: (1) NTG (30 mg/kg); (2) NICA (40 mg/kg); (3) NIMO (40 mg/kg); and (4) saline. PA training latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock (0.3 mA; 2-second duration) was automatically delivered. On day 2 latencies were recorded during a testing trial during which no shock was delivered. Latencies >900 seconds were assigned this value. Lower testing latency is indicative of an impairment of long-term associative memory. Forty-nine additional mice were randomized into similar groups for object recognition testing (ORT) and given i.p. injections on day 0. ORT measures short-term memory by exploiting the tendency of mice to prefer novel objects where a familiar object is present. On day 5 during training, 2 identical objects were placed in a circular arena and mice explored both for 15 minutes. A testing trial was conducted 1 hour later for 3 minutes after a novel object replaced a familiar one. Mice with intact memory spend about 65% of the time exploring the novel object. Mice with impaired memory devote equal time to each object. Recognition index (RI) is defined as the ratio of time spent exploring the novel object to time spent exploring both objects was the measure of memory. Mean arterial blood pressure (MAP), cerebral bloodflow, and body and brain oxygenation (PO(2)) studies were done in separate groups of mice to determine the dosages for matched degrees of hypotension and the physiological

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

PubMed

Pareja, Juan A; Montojo, Teresa; Guerrero, Ángel L; Álvarez, Mónica; Porta-Etessam, Jesús; Cuadrado, María L

2015-01-01

Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually. © 2015 American Headache Society.

Effects of hypotensive anesthesia on blood transfusion rates in craniosynostosis corrections.

PubMed

Fearon, Jeffrey A; Cook, T Kevin; Herbert, Morley

2014-05-01

Hypotensive anesthesia is routinely used during craniosynostosis corrections to reduce blood loss. Noting that cerebral oxygenation levels often fell below recommended levels, the authors sought to measure the effects of hypotensive versus standard anesthesia on blood transfusion rates. One hundred children undergoing craniosynostosis corrections were randomized prospectively into two groups: a target mean arterial pressure of either 50 mm Hg or 60 mm Hg. Aside from anesthesiologists, caregivers were blinded and strict transfusion criteria were followed. Multiple variables were analyzed, and appropriate statistical testing was performed. The hypotensive and standard groups appeared similar, with no statistically significant differences in mean age (46.5 months versus 46.5 months), weight (19.25 kg versus 19.49 kg), procedure [anterior remodeling (34 versus 31) versus posterior (19 versus 16)], or preoperative hemoglobin level (13 g/dl versus 12.9 g/dl). Intraoperative mean arterial pressures differed significantly (56 mm Hg versus 66 mm Hg; p < 0.001). The captured cell saver amount was lower in the hypotensive group (163 cc versus 204 cc; p = 0.02), yet no significant differences were noted in postoperative hemoglobin levels (8.8 g/dl versus 9.3 g/dl). Fifteen of 100 patients (15 percent) received allogenic transfusions, but no statistically significant differences were noted in transfusion rates between the hypotensive [nine of 53 (17.0 percent)] and standard anesthesia [six of 47 (13 percent)] group (p = 0.056). No significant difference in transfusion requirements was found between hypotensive and standard anesthesia during craniosynostosis corrections. Considering potential benefits of improved cerebral blood flow and total body perfusion, surgeons might consider performing craniosynostosis corrections without hypotension. Therapeutic, II.

Historical Review of Lower Body Negative Pressure Research in Space Medicine.

PubMed

Campbell, Mark R; Charles, John B

2015-07-01

Cephalad redistribution of intravascular and extravascular fluid occurs as a result of weightlessness during spaceflight. This provokes cardiovascular, cardiopulmonary, and autonomic nervous system responses. The resulting altered functional state can result in orthostatic hypotension and intolerance upon landing and return to a gravity environment. In-flight lower body negative pressure (LBNP) transiently restores normal body fluid distribution. Early in the U.S. space program, LBNP was devised as a way to test for orthostatic intolerance. With the development of the Skylab Program and longer duration spaceflight, it was realized that it could provide a method of monitoring orthostatic intolerance in flight and predicting the post-landing orthostatic response. LBNP was also investigated not only as an in-flight cardiovascular orthostatic stress test, but also as a countermeasure to cardiovascular deconditioning on Soviet space stations, Skylab, and the Shuttle. It is still being used by the Russian program on the International Space Station as an end-of-flight countermeasure.

Clinical models of cardiovascular regulation after weightlessness

NASA Technical Reports Server (NTRS)

Robertson, D.; Jacob, G.; Ertl, A.; Shannon, J.; Mosqueda-Garcia, R.; Robertson, R. M.; Biaggioni, I.

1996-01-01

After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

Contrasting actions of pressor agents in severe autonomic failure

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Biaggioni, I.; Norman, R.; Black, B. K.; Robertson, D.

1998-01-01

BACKGROUND: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response. PATIENTS AND METHODS: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels. CONCLUSIONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.

Interaction of mianserin and some hypotensive drugs in Wistar rats.

PubMed

Górska, Dorota; Andrzejczak, Dariusz

2004-01-01

Mianserin is thought to exert little effect on the cardiovascular system. In fact its safety in comparison with tricyclic drugs is high. Various experiments gave varying results as for the influence of the drug on arterial blood pressure in people and animals. Therefore, a study was undertaken in Wistar rats to evaluate interactions of mianserin administered intraperitoneally as a single dose, and for 21 days with 3 hypotensive drugs showing different mechanism of action (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood pressure was measured with a LETICA apparatus. The results of the study revealed that administration of mianserin in normotensive rats leads to a short-term decrease in blood pressure and significantly enhanced the hypotensive effect of prazosine. Repeated doses of mianserin lead to a temporary increase in blood pressure after 2 weeks of administration. Single and repeated administration of mianserin did not change the hypotensive effect of propranolol and enalapril. Three-week therapy with mianserin significantly enhanced the hypotensive effect of prazosine.

Point-of-care ultrasound leads to diagnostic shifts in patients with undifferentiated hypotension.

PubMed

Shokoohi, Hamid; Boniface, Keith S; Zaragoza, Michelle; Pourmand, Ali; Earls, James P

2017-12-01

To assess the impact of an ultrasound hypotension protocol in identifying life-threatening diagnoses that were missed in the initial evaluation of patients with hypotension and shock. A subset of cases from a previously published prospective study of hypotensive patients who presented at the Emergency Department in a single, academic tertiary care hospital is described. An ultrasound-trained emergency physician performed an ultrasound on each patient using a standardized hypotension protocol. In each case, the differential diagnosis and management plan was solicited from the treating physician immediately before and after the ultrasound. This is a case series of patients with missed diagnoses in whom ultrasound led to a dramatic shift in diagnosis and management by detecting life threatening pathologies. Following a published prospective study of the effect on an ultrasound protocol in 118 hypotensive patients, we identified a series of cases that ultrasound protocol unexpectedly determined serious life threatening diagnoses such as Takotsubo cardiomyopathy, pulmonary embolism, pericardial effusion with tamponade physiology, abdominal aortic aneurysm and perforated viscus resulting in proper diagnoses and management. These hypotensive patients had completely unsuspected but critical diagnoses explaining their hypotension, who in every case had their management altered to target the newly identified life-threatening condition. A hypotension protocol is an optimal use of ultrasound that exemplifies "right time, right place", and impacts decision-making at the bedside. In cases with undifferentiated hypotension, ultrasound is often the most readily available option to ensure that the most immediate life-threatening conditions are quickly identified and addressed in the order of their risk potential. Copyright © 2017 Elsevier Inc. All rights reserved.

[Influence of age and gender on plasma norepinephrine changes produced by orthostatic stress].

PubMed

Arata de Bellabarba, G; Molina, C; Dávila Spinetti, D; Villarroel, V; Bellabarba, S A; Torres, A

2001-01-01

The aim of this work was to determine the effect of aging and gender on plasma norepinephrine (NE) response to orthostatic stress. Fifty-six men and sixty women non-smokers, sedentary, non-obese, were studied at supine and standing positions. On the basis of the age of the subjects, they were divided into three groups of either men or women. Group A, young, range 17-34 years, Group B, middle-age, range 40-60 years, and Group C: senescent, range 61-91 years. Senescent subjects had the highest absolute supine values of NE and significant differences between women and men were found in groups B Men: 298 +/- 15 pg/mL; Women: 348 +/- 14 pg/mL), and C (M: 386 +/- 29 pg/mL; W: 473 +/- 19 pg/mL), but not between young (M: 246 +/- 21 pg/mL; W: 261 +/- 18 pg/mL). NE increased markedly in response to the orthostatic stress but the relative (percentage) increases were smaller in the older subjects perhaps related to their elevated baseline levels. The highest percent positive variation was observed in group A (M: 85%; W: 82%). The oldest group (C), had the lowest variation (M: 23%; W: 21%). The relative increases in NE responses were not different in men and women. The orthostatic-induced variation in NE was negatively related to aging in both men and women (M: r = -0.654; p < 0.0001; W: r = -0.557; p < 0.0001). It is concluded that orthostatic stress induced rise of blood NE is attenuated by age but does not appear to be dependent on gender.

Distinctive Steady-State Heart Rate and Blood Pressure Responses to Passive Robotic Leg Exercise during Head-Up Tilt: A Pilot Study in Neurological Patients

PubMed Central

Sarabadani Tafreshi, Amirehsan; Riener, Robert; Klamroth-Marganska, Verena

2017-01-01

Introduction: Robot-assisted tilt table therapy was proposed for early rehabilitation and mobilization of patients after diseases such as stroke. A robot-assisted tilt table with integrated passive robotic leg exercise (PE) mechanism has the potential to prevent orthostatic hypotension usually provoked by verticalization. In a previous study with rather young healthy subjects [average age: 25.1 ± 2.6 years (standard deviation)], we found that PE effect on the cardiovascular system depends on the verticalization angle of the robot-assisted tilt table. In the current study, we investigated in an older population of neurological patients (a) whether they show the same PE effects as younger healthy population on the cardiovascular system at different tilt angles, (b) whether changing the PE frequency (i.e., stepping speed) influences the PE effect on the cardiovascular system, (c) whether PE could prevent orthostatic hypotension, and finally, (d) whether PE effect is consistent from day to day. Methods: Heart rate (HR), and systolic and diastolic blood pressures (sBP, dBP) in response to PE at two different tilt angles (α = 20°, 60°) with three different PE frequencies (i.e., 0, 24, and 48 steps per minute) of 10 neurological patients [average age: 68.4 ± 13.5 years (standard deviation)] were measured on 2 consecutive days. Linear mixed models were used to develop statistical models and analyze the repeated measurements. Results: The models show that: PE significantly increased sBP and dBP but had no significant effect on HR. (a) Similar to healthy subjects the effect of PE on sBP was dependent on the tilt angle with higher tilt angles resulting in a higher increase. Head-up tilting alone significantly increased HR and dBP but resulted in a non-significant drop in sBP. PE, in general, had a more additive effect on increasing BP. (b) The effect of PE was not influenced by its speed. (c) Neither during head-up tilt alone nor in combination with PE did participants

Distinctive Steady-State Heart Rate and Blood Pressure Responses to Passive Robotic Leg Exercise during Head-Up Tilt: A Pilot Study in Neurological Patients.

PubMed

Sarabadani Tafreshi, Amirehsan; Riener, Robert; Klamroth-Marganska, Verena

2017-01-01

Introduction: Robot-assisted tilt table therapy was proposed for early rehabilitation and mobilization of patients after diseases such as stroke. A robot-assisted tilt table with integrated passive robotic leg exercise (PE) mechanism has the potential to prevent orthostatic hypotension usually provoked by verticalization. In a previous study with rather young healthy subjects [average age: 25.1 ± 2.6 years (standard deviation)], we found that PE effect on the cardiovascular system depends on the verticalization angle of the robot-assisted tilt table. In the current study, we investigated in an older population of neurological patients (a) whether they show the same PE effects as younger healthy population on the cardiovascular system at different tilt angles, (b) whether changing the PE frequency (i.e., stepping speed) influences the PE effect on the cardiovascular system, (c) whether PE could prevent orthostatic hypotension, and finally, (d) whether PE effect is consistent from day to day. Methods: Heart rate (HR), and systolic and diastolic blood pressures (sBP, dBP) in response to PE at two different tilt angles (α = 20°, 60°) with three different PE frequencies (i.e., 0, 24, and 48 steps per minute) of 10 neurological patients [average age: 68.4 ± 13.5 years (standard deviation)] were measured on 2 consecutive days. Linear mixed models were used to develop statistical models and analyze the repeated measurements. Results: The models show that: PE significantly increased sBP and dBP but had no significant effect on HR. (a) Similar to healthy subjects the effect of PE on sBP was dependent on the tilt angle with higher tilt angles resulting in a higher increase. Head-up tilting alone significantly increased HR and dBP but resulted in a non-significant drop in sBP. PE, in general, had a more additive effect on increasing BP. (b) The effect of PE was not influenced by its speed. (c) Neither during head-up tilt alone nor in combination with PE did participants

Aerobic fitness and orthostatic tolerance: Evidence against an association

NASA Technical Reports Server (NTRS)

Ebert, Thomas J.

1994-01-01

This presentation will focus on only one side of the debate as to whether high levels of aerobic fitness have a deleterious effect on tolerance to gravitational stress. This issue was raised in the early 1970's as a result of two research publications. The first work investigated the carotid sinus baroreflex of humans with an airtight chamber that surrounded the head and neck. The steady-state reflex changes in blood pressure that were recorded 3 minutes after application of the head and neck stimuli, were attenuated in an athletic group compared to a sedentary group of volunteers. A second report in the NASA literature indicated that five endurance-trained runners were less tolerant to LBNP than five nonrunners. These early research findings have stimulated a considerable amount of interest that has lead to a growing number of research efforts seeking an association between aerobic fitness and orthostatic tolerance in humans. I will briefly review some of the more pertinent published research information which suggests that there is no relationship between aerobic fitness and orthostatic tolerance in humans.

Spontaneous cerebrospinal fluid leak from an anomalous thoracic nerve root: case report.

PubMed

Lopez, Alejandro J; Campbell, Robert K; Arnaout, Omar; Curran, Yvonne M; Shaibani, Ali; Dahdaleh, Nader S

2016-12-01

The authors report the case of a 28-year-old woman with a spontaneous cerebrospinal fluid leak from the sleeve of a redundant thoracic nerve root. She presented with postural headaches and orthostatic symptoms indicative of intracranial hypotension. CT myelography revealed that the lesion was located at the T-11 nerve root. After failure of conservative management, including blood patches and thrombin glue injections, the patient was successfully treated with surgical decompression and ligation of the duplicate nerve, resulting in full resolution of her orthostatic symptoms.

Development of lower body negative pressure as a countermeasure for orthostatic intolerance

NASA Technical Reports Server (NTRS)

Fortney, Suzanne M.

1991-01-01

Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed toward increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP.

Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled hypotension.

PubMed

Kikuta, Y; Ohiwa, E; Okada, K; Watanabe, A; Haruki, S

1999-01-01

In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.

Skin cooling maintains cerebral blood flow velocity and orthostatic tolerance during tilting in heated humans

NASA Technical Reports Server (NTRS)

Wilson, Thad E.; Cui, Jian; Zhang, Rong; Witkowski, Sarah; Crandall, Craig G.

2002-01-01

Orthostatic tolerance is reduced in the heat-stressed human. The purpose of this project was to identify whether skin-surface cooling improves orthostatic tolerance. Nine subjects were exposed to 10 min of 60 degrees head-up tilting in each of four conditions: normothermia (NT-tilt), heat stress (HT-tilt), normothermia plus skin-surface cooling 1 min before and throughout tilting (NT-tilt(cool)), and heat stress plus skin-surface cooling 1 min before and throughout tilting (HT-tilt(cool)). Heating and cooling were accomplished by perfusing 46 and 15 degrees C water, respectively, though a tube-lined suit worn by each subject. During HT-tilt, four of nine subjects developed presyncopal symptoms resulting in the termination of the tilt test. In contrast, no subject experienced presyncopal symptoms during NT-tilt, NT-tilt(cool), or HT-tilt(cool). During the HT-tilt procedure, mean arterial blood pressure (MAP) and cerebral blood flow velocity (CBFV) decreased. However, during HT-tilt(cool), MAP, total peripheral resistance, and CBFV were significantly greater relative to HT-tilt (all P < 0.01). No differences were observed in calculated cerebral vascular resistance between the four conditions. These data suggest that skin-surface cooling prevents the fall in CBFV during upright tilting and improves orthostatic tolerance, presumably via maintenance of MAP. Hence, skin-surface cooling may be a potent countermeasure to protect against orthostatic intolerance observed in heat-stressed humans.

Effect of prolonged LBNP and saline ingestion on plasma volume and orthostatic responses during bed rest

NASA Technical Reports Server (NTRS)

Fortney, Suzanne M.; Dussack, Larry; Rehbein, Tracy; Wood, Margie; Steinmann, Laura

1991-01-01

Orthostatic intolerance remains a significant problem following space flight despite frequent use of the saline fluid-loading countermeasure and volitional use of an anti-gravity suite during reentry and landing. The purpose of this project is to examine the plasma volume (PV), endocrine, and orthostatic responses of bedrested subjects following 2-hr and 4-hr treatments of lower body negative pressure (LBNP) and saline ingestion. Ten healthy men were randomly assigned into 2 groups. Group A underwent a 4-hr LBNP/saline treatment on best rest day 5 and the 2-hr treatment on day 11. Group B underwent the 2-hr treatment on day 6 and the 4-hr treatment on day 10. Blood volume was determined before and after bed rest using radiolabelling. Changes in PV between measurements were calculated from changes in hematocrit and estimated red cell volume. Urinary excretion of anti-diuretic hormone (ADH) and aldosterone (ALD) were measured each day during the study. Orthostatic responses were measured using a ramp LBNP protocol before bed rest, before each treatment, and 24 hours after each treatment. Both 2-hr and 4-hr treatments resulted in a restoration of PV to pre-bed rest levels which persisted at least 24 hours. This increase in PV was associated with significant increases in urinary excretion of ADH and ALD. Twenty-four hours after the 4-hr treatment, the heart rate and pulse pressure response to LBNP were significantly lower and stroke volumes during LBNP were increased. Twenty-four hours after the 2-hr treatment, there was no evidence of improvement in orthostatic responses. These results suggest that a countermeasure which simply restores PV during space flight may not be sufficient for restoring orthostatic responses.

Orthostatic hypertension as a predisposing factor for masked hypertension: the J-SHIPP study.

PubMed

Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro; Ohyagi, Yasumasa; Matsuda, Fumihiko; Kohara, Katsuhiko

2016-09-01

Masked hypertension (HT) is a known risk factor for cardiovascular outcomes. Postural blood pressure (BP) dysregulation is another BP phenomenon representing cardiovascular frailty. Given their several shared risk factors, we suspected an inter-relationship between these two BP phenomena. Here we investigated a possible relationship between masked HT and postural BP dysregulation in a general population. Study subjects were 884 apparently healthy individuals (aged 66.3±8.9 years). Masked HT was assessed on the basis of the ambulatory monitored average awake BP and office-measured BP values. Orthostatic BP change was measured at our office after a subject was asked to actively stand up. A strong inverse relationship was noted for orthostatic systolic BP (SBP) change and office-to-awake SBP differences (office-awake BP) (r=-0.422, P<0.001), and these relationships were replicated in the second-visit measurements (n=101, r=-0.326, P=0.001). Multivariate analysis revealed that the inverse association was independent (β=-0.23, P<0.001) of possible covariates, including baseline office BP and antihypertensive treatment. Orthostatic HT (OHT), which is defined as postural increases in SBP >10 mm Hg, 3 min after standing (P=0.001), but not transient HT at only 1 min (P=0.767), was associated with greater office-to-awake SBP differences than in orthostatic normotensive subjects. Among apparently normotensive subjects, the frequency of masked HT was therefore significantly greater in subjects who showed OHT 3 min after standing (52.1%) compared with controls (27.5%) (odds ratio=3.01, P=0.001). We observed an intra-individual relationship between the postural BP change and the office-to-awake BP differences, and subjects who showed OHT were likely to have masked HT irrespective of antihypertensive treatment.

Speed of Heart Rate Recovery in Response to Orthostatic Challenge.

PubMed

McCrory, Cathal; Berkman, Lisa F; Nolan, Hugh; O'Leary, Neil; Foley, Margaret; Kenny, Rose Anne

2016-08-19

Speed of heart rate recovery (HRR) may serve as an important biomarker of aging and mortality. To examine whether the speed of HRR after an orthostatic maneuver (ie, active stand from supine position) predicts mortality. A longitudinal cohort study involving a nationally representative sample of community-dwelling older individuals aged ≥50 years. A total of 4475 participants completed an active stand at baseline as part of a detailed clinic-based cardiovascular assessment. Beat-to-beat heart rate and blood pressure responses to standing were measured during a 2-minute window using a finometer and binned in 10-s intervals. We modeled HRR to the stand by age group, cardiovascular disease burden, and mortality status using a random effects model. Mortality status during a mean follow-up duration of 4.3 years served as the primary end point (n=138). Speed of HRR in the immediate 20 s after standing was a strong predictor of mortality. A 1-bpm slower HRR between 10 and 20 s after standing increased the hazard of mortality by 6% controlling for established risk factors. A clear dose-response relationship was evident. Sixty-nine participants in the slowest HRR quartile died during the observation period compared with 14 participants in the fastest HRR quartile. Participants in the slowest recovery quartile were 2.3× more likely to die compared with those in the fastest recovery quartile. Speed of orthostatic HRR predicts mortality and may aid clinical decision making. Attenuated orthostatic HRR may reflect dysregulation of the parasympathetic branch of the autonomic nervous system. © 2016 American Heart Association, Inc.

Reliability of oscillometric central hemodynamic responses to an orthostatic challenge.

PubMed

Stoner, Lee; Bonner, Chantel; Credeur, Daniel; Lambrick, Danielle; Faulkner, James; Wadsworth, Daniel; Williams, Michelle A

2015-08-01

Monitoring central hemodynamic responses to an orthostatic challenge may provide important insight into autonomic nervous system function. Oscillometric pulse wave analysis devices have recently emerged, presenting clinically viable options for investigating central hemodynamic properties. The purpose of the current study was to determine whether oscillometric pulse wave analysis can be used to reliably (between-day) assess central blood pressure and central pressure augmentation (augmentation index) responses to a 5 min orthostatic challenge (modified tilt-table). Twenty healthy adults (26.4 y (SD 5.2), 55% F, 24.7 kg/m(2) (SD 3.8)) were tested on 3 different mornings in the fasted state, separated by a maximum of 7 days. Central hemodynamic variables were assessed on the left arm using an oscillometric device. Repeated measures analysis of variance indicated a significant main effect of the modified tilt-table for all central hemodynamic variables (P < 0.001). In response to the tilt, central diastolic pressure increased by 4.5 mmHg (CI: 2.6, 6.4), central systolic blood pressure increased by 2.3 (CI: 4.4, 0.16) mmHg, and augmentation index decreased by an absolute - 5.3%, (CI: -2.7, -7.9%). The intra-class correlation coefficient values for central diastolic pressure (0.83-0.86), central systolic blood pressure (0.80-0.87) and AIx (0.79-0.82) were above the 0.75 criterion in both the supine and tilted positions, indicating excellent between-day reliability. Central hemodynamic responses to an orthostatic challenge can be assessed with acceptable between-day reliability using oscillometric pulse wave analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Orthostatic responses at 4860 m in low, moderate, and high altitude residents.

PubMed

Davis, John E; Wagner, Dale R; Thorington, Jessica; Schall, Cory

2013-09-01

This study evaluated the influence of altitude of residence on orthostatic responses when exposed to high altitude. Data collection took place at the Carrel hut (4860 m) on Chimborazo in Ecuador. After being transported to the hut by vehicle, 69 people volunteered for the study. A 3-min stand test (rapid change from supine to standing) provided an orthostatic challenge while resting heart rate (RHR), systolic (SBP) and diastolic (DBP) blood pressures, and arterial oxygen saturation (SpO2) were measured. Participants were separated into four groups based on altitude of residence and ethnicity: LOW (<1500 m; n=15), MOD (1500-3000 m, n=30), and HIGH (>3000 m, n=11) Ecuadorians, and non-Ecuadorian lowlanders (NE-LOW, n=13). Supine and standing RHRs were lower (p<0.05) for HIGH compared to other groups. Furthermore, standing increased RHR in LOW, MOD, and NE-LOW by 11.9 ± 5.3, 9.5 ± 4.1, and 11.6 ± 7.4 bpm, respectively, while HIGH stayed the same (0.6 bpm increase ± 3.3). Additionally, mean arterial pressure decreased slightly but not significantly upon standing in all groups except HIGH. The difference in Spo2 among groups was not significant (p>0.05). Altitude of residence influences the cardiovascular responses to orthostatic stress with HIGH having blunted responses and greater tolerance.

Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

Hakim, Alan; O'Callaghan, Chris; De Wandele, Inge; Stiles, Lauren; Pocinki, Alan; Rowe, Peter

2017-03-01

Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS-related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt-table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non-pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short-term physiological studies. Pharmacologic therapy is indicated for patients with moderate-severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more general evaluation and on-going management and support. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The influence of water ingestion on postexercise hypotension and standing haemodynamics.

PubMed

Mendonca, Goncalo V; Fernhall, Bo

2016-11-01

In young healthy adults, postexercise hypotension (PEH) occurs after a single bout of dynamic exercise due to peripheral vasodilation. Gravitational stress may further aggravate the magnitude of PEH, thus predisposing to orthostatic intolerance. As water drinking activates sympathetic vasoconstriction, it might offset PEH via enhanced α-adrenergic vascular responsiveness. We hypothesized that water ingestion before exercise would decrease the magnitude of PEH and improve the haemodynamic reaction to active standing postmaximal exercise. In a randomized fashion, 17 healthy adults (nine men; eight women, 21·2 ± 1·6 years) ingested 50 and 500 ml of water before completing resting, cycle ergometer and recovery protocols on two separate days. After exercise, measurements [arterial blood pressure (BP), heart rate and spectral heart rate variability (HRV)] were taken in the seated position followed by 5 min of active standing. Compared to that seen post-50 ml of water, the 500 ml volume elicited an overall increase in BP (P < 0·05). Nevertheless, the magnitude of PEH was not different after either volume of water. There was an overall bradycardic effect of water, and this was accompanied by increased high-frequency power (P < 0·05). Finally, no BP, heart rate or HRV differences were found between conditions in response to active standing. These data suggest that, despite being well preserved after maximal exercise, the water pressor response does not affect the magnitude of PEH. They also indicate that drinking 500 ml of water does not impact the BP, heart rate or HRV response to 5 min of active standing during recovery postmaximal exercise. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure.

PubMed

Kranz, P G; Tanpitukpongse, T P; Choudhury, K R; Amrhein, T J; Gray, L

2016-07-01

Patients with spontaneous intracranial hypotension often exhibit low CSF pressure and changes on brain MR imaging and/or evidence of CSF leak on myelography. We investigated whether individual imaging signs of spontaneous intracranial hypotension correlate with measured CSF pressure and how frequently these 2 markers of spontaneous intracranial hypotension were concordant. We performed a retrospective, cross-sectional study of 99 subjects with spontaneous intracranial hypotension. Prevalence of brain and myelographic imaging signs of spontaneous intracranial hypotension was recorded. CSF pressure among subjects with or without individual imaging signs was compared by using a 2-tailed t test and ANOVA. Concordance between low CSF pressure (≤6 cm H2O) and imaging was defined as the presence of the sign in a subject with low CSF pressure or absence of the sign when pressure was not low. Dural enhancement, brain sagging, and venous distension sign were present in 83%, 61%, and 75% of subjects, respectively, and myelographic evidence of CSF leak was seen in 55%. Marginal correlations between CSF pressure and brain sagging (P = .046) and the venous distension sign (P = .047) were found. Dural enhancement and myelographic evidence of leak were not significantly correlated with CSF pressure. Rates of concordance between imaging signs and low CSF pressure were generally low, ranging from 39% to 55%. Brain and myelographic signs of spontaneous intracranial hypotension correlate poorly with CSF pressure. These findings reinforce the need to base the diagnosis of spontaneous intracranial hypotension on multiple diagnostic criteria and suggest the presence of patient-specific variables that influence CSF pressure in these individuals. © 2016 by American Journal of Neuroradiology.

Heart rate variability and short duration spaceflight: relationship to post-flight orthostatic intolerance

PubMed Central

Blaber, Andrew P; Bondar, Roberta L; Kassam, Mahmood S

2004-01-01

Background Upon return from space many astronauts experience symptoms of orthostatic intolerance. Research has implicated altered autonomic cardiovascular regulation due to spaceflight with further evidence to suggest that there might be pre-flight autonomic indicators of post-flight orthostatic intolerance. We used heart rate variability (HRV) to determine whether autonomic regulation of the heart in astronauts who did or did not experience post-flight orthostatic intolerance was different pre-flight and/or was differentially affected by short duration (8 – 16 days) spaceflight. HRV data from ten-minute stand tests collected from the 29 astronauts 10 days pre-flight, on landing day and three days post-flight were analysed using coarse graining spectral analysis. From the total power (PTOT), the harmonic component was extracted and divided into high (PHI: >0.15 Hz) and low (PLO: = 0.15 Hz) frequency power regions. Given the distribution of autonomic nervous system activity with frequency at the sinus node, PHI/PTOT was used as an indicator of parasympathetic activity; PLO/PTOT as an indicator of sympathetic activity; and, PLO/PHI as an estimate of sympathovagal balance. Results Twenty-one astronauts were classified as finishers, and eight as non-finishers, based on their ability to remain standing for 10 minutes on landing day. Pre-flight, non-finishers had a higher supine PHI/PTOT than finishers. Supine PHI/PTOT was the same pre-flight and on landing day in the finishers; whereas, in the non-finishers it was reduced. The ratio PLO/PHI was lower in non-finishers compared to finishers and was unaffected by spaceflight. Pre-flight, both finishers and non-finishers had similar supine values of PLO/PTOT, which increased from supine to stand. Following spaceflight, only the finishers had an increase in PLO/PTOT from supine to stand. Conclusions Both finishers and non-finishers had an increase in sympathetic activity with stand on pre-flight, yet only finishers

Comparison of 70 deg tilt, LBNP, and passive standing as measures of orthostatic tolerance

NASA Technical Reports Server (NTRS)

Hyatt, K. H.; Jacobson, L. B.; Schneider, V. S.

1975-01-01

The present study was performed to assess the reliability of lower body negative pressure (LBNP) as a test of orthostatic tolerance. The need for this assessment arose from the prior observation in this laboratory that some subjects show wide day-to-day variation in heart rate responses to LBNP. The extent of these variations was so great as to raise a serious question as to the value of LBNP as a measure of study-induced alterations (e.g., those produced by bedrest or weightlessness) in orthostatic tolerance. Five healthy volunteers were subjected to a series of tests, consisting of 70 deg tilt, LBNP, and passive standing, on three occasions preceding and three occasions following a 2-week period of bedrest. Study results show that it is possible to subdivide the volunteers into subgroups which show either great or little day-to-day variability in any of the three tests. All three tests revealed bedrest-induced alterations in orthostatic tolerance quite adequately. Of the three tests studied, LBNP most frequently resulted in the largest test-induced heart rate alterations, followed by quiet standing and, finally 70 deg tilt.

Role of the cerebellum and the vestibular apparatus in regulation of orthostatic reflexes in the cat

NASA Technical Reports Server (NTRS)

Doba, N.; Reis, D. J.

1974-01-01

The contribution of the fastigial nucleus and the vestibular nerves (eighth cranial nerves) to the orthostatic reflexes in anesthetized, paralyzed cats was studied. Bilateral lesions of the rostral fastigial nucleus resulted in impairment of the reflex changes in blood pressure, femoral arterial flow, and resistance evoked by head-up tilting to 30 deg or 60 deg. The rostral fastigial nucleus, which might be triggered by the vestibular apparatus, appears to participate in concert with the baroreceptors in the initiation and possibly the maintenance of the orthostatic reflexes.

Vasopressor choice for hypotension in elective Cesarean section: ephedrine or phenylephrine?

PubMed Central

Gunda, Chandrakala P.; Malinowski, Jennifer; Tegginmath, Aruna; Suryanarayana, Venkatesh G.

2010-01-01

Introduction Hypotensive episodes are a common complication of spinal anesthesia during Cesarean section. The purpose of this study was to compare the effectiveness and the side effects of vasopressors, ephedrine and phenylephrine, administered for hypotension during elective Cesarean section under spinal anesthesia. Material and methods The study consisted of 100 selected ASA I/II females scheduled for elective Cesarean section under spinal anesthesia. Each patient was randomly assigned to one of the two double-blind study groups. Group E received 1 ml ephedrine (5 mg/ml) with normal saline if hypotension was present (n=50). Group P received 1 ml phenylephrine (100 µg/ml) with normal saline if hypotension developed (n=50). Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) were compared within and between groups to basal levels at time increments of 0, 2, 4, 6, 8, 10, 15, 20, 25, 30, 45, and 60 min from start of surgery. Incidence of side effects and neonatal outcomes were studied between groups. Results All patients required vasopressor therapy for hypotension. Administration of phenylephrine was associated with significant drop in HR. Changes in SBP, DBP, and MAP were similar in both groups for most observed times. The incidences of nausea/vomiting and tachycardia were significantly higher in the ephedrine group. Conclusions Phenylephrine and ephedrine are acceptable choices to combat maternal hypotension related to spinal anesthesia in elective Cesarean section. Complications of intra-operative nausea and vomiting, tachycardia and bradycardia should be considered when choosing a vasopressor, suggesting phenylephrine may be more appropriate when considering maternal well-being. PMID:22371756

Central Methysergide Prevents Renal Sympathoinhibition and Bradycardia during Hypotensive Hemorrhage

NASA Technical Reports Server (NTRS)

Veelken, Roland; Johnson, Kim; Scrogin, Karie E.

1998-01-01

Central methysergide prevents renal sympathoinhibition and bradycardia during hypotensive hemorrhage. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured in conscious rats during either hemorrhage or cardiopulmonary receptor stimulation with phenylbiguanide (PBG) after intracerebroventricular injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (40 microg). Progressive hemorrhage caused an initial rise (109 +/- 33%) followed by a fall in RSNA (-60 +/- 7%) and a fall in HR (-126 +/- 7 beats/min). Methysergide delayed the hypotension and prevented both the sympathoinhibitory and bradycardic responses to hemorrhage. Systemic 5-HT3-receptor blockade did not influence responses to hemorrhage. The PBG infusion caused transient depressor(-25 +/- 6 mmHg), bradycardic (-176 +/- 40 beats/min), and renal sympathostimulatory (182 +/-47% baseline) responses that were not affected by central methysergide (-20 +/- 6 mmHg, -162 +/- 18 beats/min, 227 +/- 46% baseline). These data indicate that a central serotonergic receptor-mediated component contributes to the sympathoinhibitory and bradycardic responses to hypotensive hemorrhage in conscious rats. Furthermore, the same central 5-HT-receptor populations involved in reflex responses to hypotensive hemorrhage probably do not mediate the sympathoinhibitory response to cardiopulmonary chemosensitive 5-HT3 receptors.

Effects of weight-based ultrafiltration rate limits on intradialytic hypotension in hemodialysis.

PubMed

Pirkle, James L; Comeau, Mary E; Langefeld, Carl D; Russell, Gregory B; Balderston, Somer S; Freedman, Barry I; Burkart, John M

2018-04-01

High ultrafiltration (UF) rates can result in intradialytic hypotension and are associated with increased mortality. The effects of a weight-based UF rate limit on intradialytic hypotension and the potential for unwanted fluid weight gain and hospitalizations for volume overload are unknown. This retrospective cohort study examined 123 in-center hemodialysis patients at one facility who transitioned to 13 mL/kg/h maximum UF rates. Patients were studied for an 8 week UF rate limit exposure period and compared to the 8-week period immediately prior, during which the cohort served as its own historical control. The primary outcomes were frequency of intradialytic hypotension events and percentage of treatments with a hypotension event. The delivered UF rate was lower during the exposure compared to the baseline period (mean UF rate 7.90 ± 4.45 mL/kg/h vs. 8.92 ± 5.64 mL/kg/h; P = 0.0005). The risk of intradialytic hypotension was decreased during the exposure compared to baseline period (event rate per treatment 0.0569 vs. 0.0719, OR 0.78 [95% CI 0.62-1.00]; P = 0.0474), as was the risk of having a treatment with a hypotension event (percentage of treatments with event 5.2% vs. 6.8%, OR 0.75 [95% CI 0.58-0.96]; P = 0.0217). Subgroup analyses demonstrated that these findings were attributable to patients with high baseline UF rates. Statistically significant differences in all-cause or volume overload-related hospitalization were not observed during the exposure period. A weight-based UF rate limit of 13 mL/kg/h was associated with a decrease in the rate of intradialytic hypotension events among in-center hemodialysis patients. © 2017 International Society for Hemodialysis.

Permissive hypotension in extremely low birth weight infants (≤1000 gm).

PubMed

Ahn, So Yoon; Kim, Eun Sun; Kim, Jin Kyu; Shin, Jeong Hee; Sung, Se In; Jung, Ji Mi; Chang, Yun Sil; Park, Won Soon

2012-07-01

We performed this study to evaluate the safety of permissive hypotension management in extremely low birth weight infants (ELBWIs). Medical records of all inborn ELBWIs admitted to Samsung Medical Center from January 2004 to December 2008 were reviewed retrospectively. Of a total of 261 ELBWIs, 47 (18%) required treatment for hypotension (group T), 110 (42%) remained normotensive (group N), and 104 (40%) experienced more than one episode of hypotension without treatment (group P) during the first 72 hours of life. Treatment of hypotension included inotropic support and/or fluid loading. Birth weight and Apgar scores were significantly lower in the T group than the other two groups. In the N group, the rate of pathologically confirmed maternal chorioamnionitis was significantly higher than other two groups, and the rate was higher in the P group than the T group. After adjusting for covariate factors, no significant differences in mortality and major morbidities were found between the N and P groups. However, the mortality rate and the incidence of intraventricular hemorrhage (≥stage 3) and bronchopulmonary dysplasia (≥moderate) were significantly higher in the T group than the other two groups. Long term neurodevelopmental outcomes were not significantly different between the N and P groups. Close observation of hypotensive ELBWIs who showed good clinical perfusion signs without intervention allowed to avoid unnecessary medications and resulted in good neurological outcomes.

Bacteriological Controls at Czechoslovakia Blood Transfusion Centers.

DTIC Science & Technology

1961-07-01

and are followed by a steep rise in temperature. 3. The third phase is characterized by extreme distension of the arteries well visible in the mucous...by increased muscular rigidity. 4. The fourth phase is of shock, disappearance of vasomotor regulation, strong orthostatic hypotension with peripheral

Blood volume and orthostatic responses of men and women to a 13-day bedrest

NASA Technical Reports Server (NTRS)

Fortney, S.; Driscoll, T.; Steinmann, L.; Alfrey, C.

1992-01-01

Changes in blood volume during space flight are thought to contribute to decrements in postflight orthostatic function. The purpose of this study was to determine whether gender affects red cell mass and plasma volume during a short exposure to simulated microgravity, and whether gender differences in orthostatic tolerance ensure. Methods: Ten men (31.5 plus or minus 5.2 years, STD) and eleven normally menstruating women (33.3) plus or minus 6.0 STD) underwent 13 days of 6 degree head-down bedrest. Plasma volume (Iodine 125 labeled human serum albumin) and red cell mass (Carbon 51 labeled red blood cells) were measured before bedrest and on bedrest day 13. On the same days, orthostatic tolerance (OT) was determined as the maximal pressure during a presyncopalimited lower body negative pressure test. Results: Plasma volume (PV) and red cell mass (RCM) decreased in both groups with a greater PV decrease (P less than 0.05) in men (6.3 plus or minus 0.7 ml/kg) than in women (4.1 plus or minus 0.6 ml/kg). Decreases in red cell mass were similar (1.7 plus or minus 0.2 ml/kg in men and 1.7 plus or minus 0.2 ml/kg in women). OT was similar for men and women before bedrest (minus 78 plus or minus 6 mmHg in men versus minus 70 plus or minus 4 mmHg in women) and decreased by a similar degree (by an average of 11 mmHg in both groups) after bedrest. The changes in OT did not correlate with changes in plasma volume during bedrest (r(exp 2) = 0.002). Conclusion: Thus, although female hormones may protect PV during bedrest, they do no appear to offer an advantage in terms of loss of orthostatic function.

Prehospital Nitroglycerin in Tachycardic Chest Pain Patients: A Risk for Hypotension or Not?

PubMed

Proulx, Marie-Hélène; de Montigny, Luc; Ross, Dave; Vacon, Charlene; Juste, Louis Enock; Segal, Eli

2017-01-01

The American Heart Association guidelines (AHA) guidelines list tachycardia as a contraindication for the administration of nitroglycerin (NTG), despite limited evidence of adverse events. We sought to determine whether NTG administered for chest pain was a predictor of hypotension (systolic blood pressure <90 mmHg) in patients with tachycardia, compared to patients without tachycardia (50≥ heart rate ≤100). We performed a retrospective cohort study using patient care reports completed by basic life support (BLS) providers in a large urban Canadian EMS system for the period 2010-2012. We used logistic regression to test the association between post-NTG hypotension and tachycardia, independent of pre-NTG blood pressure, age, sex, and comorbidities. Using identical models, we tested four secondary outcomes (drop in blood pressure, reduced consciousness, bradycardia, and cardiac arrest). The cohort included 10,308 patients who were administered NTG by BLS in the prehospital setting; 2,057 (20%) of patients were tachycardic before NTG administration. Hypotension occurred in 320 of all patients (3.1%): 239 without tachycardia (2.9%) and 81 with tachycardia (3.9%). Compared to non-tachycardic patients, tachycardic patients showed increased adjusted odds of hypotension (AOR: 1.60; 95% CI: 1.23-2.08) or of a drop in blood pressure of 30mm Hg or greater (AOR: 1.11; CI: 1.00-1.24). Tachycardia was associated with decreased odds of bradycardia (OR: 0.33; CI: 0.17-0.64). We did not find a significant association between tachycardia and either post-NTG reduced level of consciousness or cardiac arrest. We did find a strong, significant association between pre-NTG blood pressure and post-NTG hypotension (AOR for units of 10mmHg: 0.64; CI: 0.61-0.69). Hypotension following prehospital administration of NTG was infrequent in patients with chest pain. However, while the absolute risk of NTG-induced hypotension was low, patients with pre-NTG tachycardia had a significant increase

Use of Minute-by-Minute Cardiovascular Measurements During Tilt Tests to Strengthen Inference on the Effect of Long-Duration Space Flight on Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Feiveson, Alan H.; Lee, Stuart M. C.; Stenger, Michael B.; Stein, Sydney P.; Platts, Steven H.

2011-01-01

Typical methodology for evaluating the effects of spaceflight on orthostatic hypotension (OH) has been survival analysis of tolerance times from 80 head-up tilt tests. However when scheduled test durations are short, there may not be enough failures to allow survival analysis to adequately estimate and compare the effects of flight phase (e.g. pre-flight, number of days post-flight), flight duration, and their interaction, as well as interactions with effects of interventions or countermeasures. The problem is exacerbated in the presence of a repeated measures design, in which subjects participate in tilt tests during various flight phases. Here we show how it is possible to dramatically improve the efficiency of statistical inference in this setting by making use of the additional information contained in minute-by-minute observations of cardiovascular parameters thought to be reflective of progression towards presyncope during tilt testing. Methods: We retrospectively examined operational tilt test (OTT; 10 -min 80 head-up tilt) data from 20 International Space Station (ISS) and 66 Shuttle astronauts 10 d before launch (L-10), on landing day (R+0) and during recovery (R+1, R+3, R+6-10) depending on the level of participation. Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. In addition to OTT survival time, 8 cardiovascular parameters (CP: heart rate, systolic, diastolic, and mean arterial blood pressure, pulse pressure, stroke volume, cardiac output, and total peripheral resistance) that might be predictive of progression towards presyncope were measured every minute of each OTT. Statistical analysis was predicated on a two ]stage model of causation. In the first stage, flight duration and time from landing affect the astronauts' degree of OH, which is manifested in the time trends and variation of the above CPs during OTTs. In the second stage, the behavior of these parameters directly affects OTT survival

Juvenile Idiopathic Arthritis

MedlinePlus

... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

MedlinePlus

... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

Effects of oral contraceptives on sympathetic nerve activity during orthostatic stress in young, healthy women

PubMed Central

Klein, Jenna C.; Schwartz, Christopher E.

2010-01-01

Recent studies report that the menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. The purpose of the present study was to determine whether oral contraceptives (OC) influence sympathetic neural activation during an orthostatic challenge. Based on evidence that sympathetic baroreflex sensitivity (BRS) is increased during the “low hormone” (LH) phase (i.e., placebo pills) in women taking OC, we hypothesized an augmented muscle sympathetic nerve activity (MSNA) response to orthostatic stress during the LH phase. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP; −5, −10, −15, −20, −30, −40 mmHg; 3 min/stage) in 12 healthy women taking OC (age 22 ± 1 years). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA. Subjects were examined twice: once during LH phase and once ∼3 wk after LH during the “high hormone” phase (randomized order). Resting MSNA (10 ± 2 vs. 13 ± 2 bursts/min), MAP (85 ± 3 vs. 84 ± 3 mmHg), and HR (62 ± 2 vs. 65 ± 3 beats/min) were not different between phases. MSNA and HR increased during progressive LBNP (P < 0.001), and these increases were similar between phases. Progressive LBNP did not change MAP during either phase. Sympathetic BRS increased during progressive LBNP, but these responses were not different between LH and high hormone phases. In conclusion, our results demonstrate that OCs do not alter cardiovascular and sympathetic neural responses to an orthostatic challenge in young, healthy women. PMID:19828840

Hypoalbuminemia is an important risk factor of hypotension during hemodialysis.

PubMed

Nakamoto, Hidetomo; Honda, Nobuko; Mimura, Taku; Suzuki, Hiromichi

2006-10-01

Hypotension during hemodialysis (HD) is an important problem in patients on HD. To investigate the risk factors that contribute to the hypotension during HD, we compared background factors of hypotensive (HP) patients during HD. Among 58 patients undergoing HD in Tamura Memorial Hospital, 12 patients could not continue full HD because of hypotension. We compared the data of ultrafiltration volume, cardiothoracic ratio (CTR), total protein (TP), serum albumin, blood urea nitrogen (BUN), serum creatinine, total cholesterol (TC), hemoglobin (Hb), blood glucose (BS), brain natriuretic peptide (BNP), and cardiac function between HP patients (HP group; n=12) and sex- and age-matched control patients (NP group; n=12). There were no significant differences of age, sex, and duration of HD between the 2 groups. Cardiothoracic ratio is bigger and BNP is higher in the HP group compared with the NP group (CTR: HP 55.8+/-2.9% vs. NP 47.7+/-1.1%, p=0.0165; BNP: HP 602+/-171 vs. NP 147+/-38, p=0.0167). Serum albumin in the HP group is significantly lower compared with the NP group (HP 3.2+/-0.1 g/dL vs. NP 3.5+/-0.1 g/dL, p=0.0130). However, there were no significant differences of ultrafiltration rate (UFR), BS, TC, Hb, and cardiac function between the 2 groups. There is a significant negative correlation between changes of systolic blood pressure (delta systolic blood pressure) and serum albumin in these patients (r=-0.598, p=0.0016). From these data, we conclude that hypoalbuminemia is a major risk factor of hypotension during HD.

78 FR 76308 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... neurogenic orthostatic hypotension in patients with primary autonomic failure (Parkinson's disease, multiple... recommendations to the Agency on FDA's regulatory issues. Date and Time: The meeting will be held on January 14... Agency's Web site at http://www.fda.gov/AdvisoryCommittees/default.htm and scroll down to the appropriate...

Juvenile idiopathic arthritis.

PubMed

Boros, Christina; Whitehead, Ben

2010-09-01

Juvenile idiopathic arthritis is the most common rheumatic disease in childhood, occurring in approximately 1:500 children. Despite a recent expansion in treatment options and improvement of outcomes, significant morbidity still occurs. This article outlines the clinical manifestations, assessment, detection of complications, treatment options and monitoring requirements, with the aid of guidelines recently published by The Royal Australian College of General Practitioners, which provide practical support for general practitioners to ensure best practice care and to prevent lifelong disability in patients with juvenile idiopathic arthritis. General practice plays an important role in the early detection, initial management and ongoing monitoring of children with juvenile idiopathic arthritis. Early detection involves understanding the classification framework for subtypes of juvenile idiopathic arthritis, and being aware of the clinical manifestations and how to look for them, through history, examination and appropriate investigation. The major extra-articular manifestations of juvenile idiopathic arthritis are uveitis and growth disturbance. Treatment options include nonsteroidal anti-inflammatory drugs, methotrexate, biologic agents, and corticosteroids. Management using a multidisciplinary approach can prevent long term sequelae. Unfortunately, approximately 50% of children will have active disease as adults.

Increased popliteal circumferential wall tension induced by orthostatic body posture is associated with local atherosclerotic plaques.

PubMed

Gemignani, Tiago; Azevedo, Renata C; Higa, Celina M; Coelho, Otávio R; Matos-Souza, José R; Nadruz, Wilson

2012-09-01

Lower limb arteries are exposed to higher hemodynamic burden in erectile posture. This study evaluated the effects of body posture on popliteal, carotid and brachial circumferential wall tension (CWT) and investigated the relationship between local CWT and atherosclerotic plaques in subjects with cardiovascular risk factors. Two hundred and three subjects (118 women and 85 men) with cardiovascular risk factors (smoking, hypertension or diabetes mellitus) underwent clinical and laboratory analysis and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Arteries were evaluated by ultrasound analysis, while CWT was calculated according to Laplace's law. Among the enrolled participants, 47%, 29% and none presented popliteal, carotid and brachial plaques, respectively. Carotid CWT measurements were not associated with local plaques after adjustment for potential confounders. Conversely, general linear model and logistic regression analyses adjusted for potential confounders demonstrated that peak orthostatic CWT was the only local hemodynamic parameter showing significant relationship with popliteal plaques in the whole sample. In gender-specific analyses, although positively correlated with popliteal plaques in both genders, local peak orthostatic CWT exhibited an independent association with popliteal plaques after adjustment for potential confounders only in women. Popliteal CWT measured in orthostatic posture, rather than in supine position, is associated with popliteal atherosclerotic plaques, particularly in women. These findings suggest that erectile posture might play a role in the atherogenesis of leg arteries by modifying local hemodynamic forces and that there may be gender differences in this regard. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Brazilian dentists' attitudes about medical emergencies during dental treatment.

PubMed

Arsati, Franco; Montalli, Victor Angelo; Flório, Flavia Martão; Ramacciato, Juliana Cama; da Cunha, Fernanda Lopes; Cecanho, Rodrigo; de Andrade, Eduardo Dias; Motta, Rogério Heládio Lopes

2010-06-01

The main objective of this study was to evaluate the prevalence of emergencies in dental practices and the prepared-ness and the training experience in cardiopulmonary resuscitation (CPR) of Brazilian dentists in dealing with emergencies. The volunteer participants in the study were 498 Brazilian dentists who were present at the 27th International Congress of Dentistry in São Paulo. The most prevalent emergency was presyncope (reported by 54.20 percent of respondents), followed by orthostatic hypotension (44.37 percent), moderate allergic reactions (16.86 percent), hypertensive crisis (15.06 percent), asthma (15.06 percent), syncope (12.65 percent), angina (6.82 percent), convulsion (6.22 percent), hypoglycemia (5.62 percent), hyperventilation crisis (5.22 percent), choking (2.20 percent), and cerebrovascular accident (0.8 percent). Anaphylaxis, myocardial infarction, and cardiac arrest were the rarest emergencies, reported by only 0.4, 0.2, and 0.2 percent of dentists, respectively. Only 41 percent of the dentists judged themselves capable to diagnose the cause of an emergency during a dental visit. The majority responded that they would be capable of performing initial treatment of presyncope, syncope, orthostatic hypotension, convulsion, and choking. However, most of them felt unable to treat anaphylaxis, myocardial infarction, or cardiac arrest. Further, the majority felt unable to perform CPR or undertake an intravenous injection. It was concluded that the most prevalent medical emergencies in dental practice of Brazilian dentists are presyncope and orthostatic hypotension. The occurrence of life-threatening medical emergencies like anaphylaxis, myocardial infarction, cardiac arrest, and cerebrovascular accident is rare. Brazilian dentists are not fully prepared to manage medical emergencies and have insufficient experience training in CPR.

Severe bradycardia and prolonged hypotension in ciguatera.

PubMed

Chan, Thomas Yan Keung

2013-06-01

Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

Investigation of postural hypotension due to static prolonged standing in female workers.

PubMed

Kabe, Isamu; Tsuruoka, Hiroko; Tokujitani, Yoko; Endo, Yuichi; Furusawa, Mami; Takebayashi, Toru

2007-07-01

The "Just-in-Time system" improves productivity and efficiency through cost reduction while it makes workers work in a standing posture. The aim of this study was to investigate the prevalence of postural hypotension in females during prolonged standing work, and to discuss preventive methods. Twelve female static standing workers (mean age+/-standard deviation; 32+/-14 yr old), 6 male static standing workers (30+/-4 yr old), 10 female walking workers (27+/-7 yr old) and 9 female desk workers (31+/-5 yr old) in a certain telecommunications equipment manufacturing factory agreed to participate in this study. All participants received an interview with an occupational physician, and performed the standing up test before working and ambulatory blood pressure monitoring (ABPM) while working. Although the blood pressure of the standing up test did not differ among the groups, mean pulse rates on standing up significantly increased in every group. Hypotension rates in the female standing workers' group by ABPM were 9 persons of 12 participants (75%) for systolic blood pressure (SBP), and were 11 persons of 12 participants (92%) for diastolic blood pressure (DBP). There were significantly higher than those in the female desk workers' group, none of 9 participants (0%) for SBP and 2 of 9 participants (22%) for DBP. The hypotension rates both male standing and female walking worker groups did not differ. Because all 8 workers who were found to have postural hypotension by the standing up test had decreased SBP and/or DBP by ABPM, it is suggested that persons at high risk of postural hypotension during standing work could be screened by the standing up test. The mechanism of postural hypotension may be a decrease of venous return due to leg swelling, and neurocardiogenic or vasovagal response. Preventing the congestion of the lower limbs by walking, managing standing time and wearing elastic hose to keep the amount of the venous return could prevent postural hypotension

Vocal cord paralysis: What matters between idiopathic and non-idiopathic cases?

PubMed

Özbal Koç, Ayça Eltaf; Türkoğlu, Seda Babakurban; Erol, Ozan; Erbek, Selim

2016-01-01

This study aims to evaluate the demographic and clinical characteristics of patients with idiopathic and non-idiopathic vocal cord paralysis (VCP). This retrospective cohort was performed on data extracted from medical files of 92 consecutive patients (43 males, 49 females; median age 52.1±23.1 years; min. 1 - max. 87) with VCP diagnosed in the otorhinolaryngology department between April 2012 and December 2015. Diagnoses associated with VCP, side of involvement (right, left or bilateral) and previous medical histories were noted and compared between patients with idiopathic and non-idiopathic VCP. Vocal cord paralysis occurred on the left side (n=56, 60.9%), right side (n=28, 30.4%) or bilaterally (n=8, 8.7%). A clinical entity related with VCP was identified in 63 patients (68.5%), while 29 (31.5%) patients had idiopathic VCP. Most common etiologies for VCP were thyroid surgery (n=32, 34.8%), cardiovascular surgery (n=9, 9.8%), lung cancer (n=6, 6.5%) and cardiac anomalies (n=4, 4.3%), respectively. Patients with idiopathic VCP were significantly older (p<0.001), while gender distribution (p=0.121) and side of involvement (p=0.340) did not differ between two groups. Vocal cord paralysis is a relatively common clinical entity with substantial rate of morbidity. Identification of the underlying etiology and awareness on the clinical characteristics are keystones for foreseeing complications and determining the appropriate therapeutic modality.

Comparative hemodynamic effects of hypotension induced by diadenosine tetraphosphate (AP4A) and ATP in dogs.

PubMed

Takeda, Shohei; Inada, Yutaka; Fukui, Noriyuki; Tomaru, Teruaki

1997-03-01

ATP and diadenosine tetraphosphate (AP 4 A) have been shown to produce vasodilation mediated by P 1 - and P 2 -purinoceptor, respectively. The differing mechanisms involved in this vasodilating activity may induce different systemic hemodynamic changes. We compared the hemodynamic effects of AP 4 A-induced hypotension with those induced by ATP. Fourteen mongrel dogs were anesthetized with 0.87% halothane in oxygen (1 MAC). After the baseline period, mean arterial pressure was reduced to 60 mmHg for 60 min by the infusion of AP 4 A or ATP. The ATP- and AP 4 A-induced hypotension resulted in a maximum reduction in systemic vascular resistance of 43% and 46%, respectively (P<0.01), associated with a significant increase in stroke volume index. With ATP, a 20% of maximum increase (P<0.05) in cardiac index (CI) was observed during the induced hypotension. In contrast, AP 4 A-induced hypotension did not result in any changes in CI throughout the observation period. The varying results concerning CI during the ATP- and AP 4 A-induced hypotension were probably due to differences in ventricular filling pressure, since AP 4 A-induced hypotension was associated with decreases (P<0.01) in both right atrial and pulmonary capillary wedge pressures, whereas neither of these variables significantly changed with ATP. The hypotension induced by either ATP or AP 4 A was associated with a significant decrease in heart rate (HR). However, both the magnitude and duration of decreases in HR due to ATP-induced hypotension were more pronounced than those seen with AP 4 A. In conclusion, while both drugs were equally capable of inducing hypotension, our results suggest that AP 4 A was more suitable for induced hypotension because of its potent vasodilatory action with venodilation and less negative chronotropic action.

A sequential compression mechanical pump to prevent hypotension during elective cesarean section under spinal anesthesia.

PubMed

Sujata, N; Arora, D; Panigrahi, B P; Hanjoora, V M

2012-04-01

Spinal anesthesia is a standard technique for cesarean section but can cause hypotension which may be related to venous pooling secondary to progesterone-induced decreases in vascular tone. This study investigated the use of a sequential compression mechanical pump with thigh-high sleeves with compression cycles timed to venous refilling. We hypothesized that this would recruit pooled venous blood from the lower limbs, maintain the central blood volume and thus decrease the incidence of hypotension. One hundred parturients scheduled for elective cesarean section under spinal anesthesia were recruited and randomly assigned to use of either a mechanical pump (Group M) or control (Group C). A standardized protocol for co-hydration and anesthesia was followed. Hypotension, defined as a decrease in systolic blood pressure by >20% from baseline, was treated with 6-mg boluses of intravenous ephedrine. The incidence of hypotension was defined as the primary outcome. Median ephedrine requirement was taken as a measure of the severity of hypotension. Hypotension occurred in 12 of 47 (25.5%) patients in Group M compared to 27 of 45 (60%) in Group C (P=0.001). The median [range] ephedrine dose was greater in Group C (12 [0-24]mg) compared to Group M (0 [0-12]mg) (P<0.001). There was no difference between groups in the time to onset of hypotension. The use of a sequential compression mechanical pump that detects venous refilling and cycles accordingly, reduced the incidence and severity of hypotension after spinal anesthesia for cesarean section. Copyright © 2012 Elsevier Ltd. All rights reserved.

Idiopathic hypersomnia.

PubMed

Billiard, Michel; Sonka, Karel

2016-10-01

Idiopathic hypersomnia continues to evolve from the concept of "sleep drunkenness" introduced by Bedrich Roth in Prague in 1956 and the description of idiopathic hypersomnia with two forms, polysymptomatic and monosymptomatic, by the same Bedrich Roth in 1976. The diagnostic criteria of idiopathic hypersomnia have varied with the successive revisions of the International classifications of sleep disorders, including the recent 3rd edition. No epidemiological studies have been conducted so far. Disease onset occurs most often during adolescence or young adulthood. A familial background is often present but rigorous studies are still lacking. The key manifestation is hypersomnolence. It is often accompanied by sleep of long duration and debilitating sleep inertia. Polysomnography (PSG) followed by a multiple sleep latency test (MSLT) is mandatory, as well as a 24 h PSG or a 2-wk actigraphy in association with a sleep log to ensure a total 24-h sleep time longer than or equal to 66O minutes, when the mean sleep latency on the MSLT is longer than 8 min. Yet, MSLT is neither sensitive nor specific and the polysomnographic diagnostic criteria require continuous readjustment and biologic markers are still lacking. Idiopathic hypersomnia is most often a chronic condition though spontaneous remission may occur. The condition is disabling, sometimes even more so than narcolepsy type 1 or 2. Based on neurochemical, genetic and immunological analyses as well as on exploration of the homeostatic and circadian processes of sleep, various pathophysiological hypotheses have been proposed. Differential diagnosis involves a number of diseases and it is not yet clear whether idiopathic hypersomnia and narcolepsy type 2 are not the same condition. Until now, the treatment of idiopathic hypersomnia has mirrored that of the sleepiness of narcolepsy type 1 or 2. The first randomized, double-blind, placebo-controlled trials of modafinil have just been published, as well as a double

Impact of Diabetes Type 1 in Children on Autonomic Modulation at Rest and in Response to the Active Orthostatic Test

PubMed Central

Giacon, Thais Roque; Vanderlei, Franciele Marques; Christofaro, Diego Giulliano Destro; Vanderlei, Luiz Carlos Marques

2016-01-01

Introduction Cardiovascular autonomic neuropathy is one of the most common complications of diabetes mellitus type 1 (DM1), of which one of the first subclinical manifestations is changes in heart rate variability (HRV). Thus, analysis of HRV associated with the autonomic active orthostatic test is important in this population. Objectives To analyze the autonomic modulation responses induced by the implementation of the active orthostatic test, in children with DM1, and study the autonomic modulation by means of HRV indices. Method Data of 35 children were analyzed, of both sexes, aged between 7 and 15 years, who were divided into two groups: Diabetic (n = 16) and Control (n = 19). The following variables were collected initially: weight, height, body fat percentage, heart rate, blood pressure and casual blood glucose. Subsequently, for analysis of autonomic modulation, the beat-to-beat heart rate was captured by a heart rate monitor in the supine position for 30 minutes and after 10 minutes standing during performance of the active orthostatic test. HRV indices were calculated in the time and frequency domains. For data analysis, covariance analysis was used to compare groups and ANOVA for repeated measures to compare the effects of the active orthostatic test. These data were adjusted for age, sex, ethnicity, body fat percentage and casual blood glucose, with a 5% significance level. Results The results suggested that diabetic children at rest present a decrease in SDNN (50.4 vs. 75.2), rMSSD (38.7 vs 57.6) and LF [ms2] (693.6 vs 1874.6). During the active orthostatic test the children in both groups demonstrated a reduction in SDNN, RMSSD and LF [ms2] compared to the resting position, and this response was less pronounced in the diabetic group. Conclusion We conclude that regardless of age, sex, ethnicity, body fat percentage and casual blood glucose, performing the active orthostatic test promoted increased sympathetic modulation and reduced parasympathetic

Impact of Diabetes Type 1 in Children on Autonomic Modulation at Rest and in Response to the Active Orthostatic Test.

PubMed

Giacon, Thais Roque; Vanderlei, Franciele Marques; Christofaro, Diego Giulliano Destro; Vanderlei, Luiz Carlos Marques

2016-01-01

Cardiovascular autonomic neuropathy is one of the most common complications of diabetes mellitus type 1 (DM1), of which one of the first subclinical manifestations is changes in heart rate variability (HRV). Thus, analysis of HRV associated with the autonomic active orthostatic test is important in this population. To analyze the autonomic modulation responses induced by the implementation of the active orthostatic test, in children with DM1, and study the autonomic modulation by means of HRV indices. Data of 35 children were analyzed, of both sexes, aged between 7 and 15 years, who were divided into two groups: Diabetic (n = 16) and Control (n = 19). The following variables were collected initially: weight, height, body fat percentage, heart rate, blood pressure and casual blood glucose. Subsequently, for analysis of autonomic modulation, the beat-to-beat heart rate was captured by a heart rate monitor in the supine position for 30 minutes and after 10 minutes standing during performance of the active orthostatic test. HRV indices were calculated in the time and frequency domains. For data analysis, covariance analysis was used to compare groups and ANOVA for repeated measures to compare the effects of the active orthostatic test. These data were adjusted for age, sex, ethnicity, body fat percentage and casual blood glucose, with a 5% significance level. The results suggested that diabetic children at rest present a decrease in SDNN (50.4 vs. 75.2), rMSSD (38.7 vs 57.6) and LF [ms2] (693.6 vs 1874.6). During the active orthostatic test the children in both groups demonstrated a reduction in SDNN, RMSSD and LF [ms2] compared to the resting position, and this response was less pronounced in the diabetic group. We conclude that regardless of age, sex, ethnicity, body fat percentage and casual blood glucose, performing the active orthostatic test promoted increased sympathetic modulation and reduced parasympathetic modulation in both groups, and this response was less

Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase.

PubMed

Gerová, M; Török, J

2004-01-01

The metabolites of arginine were recently shown to be involved in cardiovascular control. The study addresses the general cardiovascular response of anaesthetized rats to agmatine, a decarboxylated arginine. The relation between two arginine metabolic pathways governed by arginine decarboxylase and nitric oxide synthase was investigated. Intravenous administration of agmatine 30 and 60 microM/0.1 ml saline elicited remarkable hypotension of 42.6+/-4.6 and 70.9+/-6.5 mm Hg, respectively. The hypotension was characterized by long duration with half-time of return 171.6+/-2.9 and 229.2+/-3.8 s, respectively. The time of total blood pressure BP recovery was about 10 min. Dose-dependent relaxation to agmatine was also found in aorta rings in vitro. Both doses of agmatine administered 60-180 min after NO synthase inhibition L-NAME 40 mg/kg i.v. caused greater hypotension 59.0+/-7.6 and 95.8 8.8 mm Hg P<0.01 both compared to animals with intact NO synthase, but this was accompanied by a significant shortening of the half-time of BP return. If agmatine was administered to hypertensive NO-deficient rats treated with 40 mg/kg/day L-NAME for 4 weeks, similar significant enhancement of hypotension was observed at both agmatine doses, again with a significant shortening of half-time of BP return. It can be summarized that the long-lasting hypotension elicited by agmatine was amplified after acute or chronic NO synthase inhibition, indicating a feedback relation between the two metabolic pathways of arginine.

[Cerebrovenous orthostatic reactivity in pathology of the craniovertebral junction (Chiari malformation)].

PubMed

Shakhnovich, V A; Mitrofanova, E V; Shimanskiy, V N; Konovalov, N A; Shkarubo, A N

2015-01-01

Chiari malformation is characterized by herniation of the cerebellar tonsils into the foramen magnum, which leads to disturbance of CSF circulation through the craniovertebral junction. Orthostatic stress, which leads to the movement of SCF through the craniovertebral junction, is an adequate method to detect these disorders. It is accompanied by changes in the intracranial pressure, affecting the cerebrovenous orthostatic reactivity (CVOR), which is noninvasively assessed in patients with Chiari malformation. The study involved 35 patients with Chiari malformation (26 patients with Chiari I and 9 patients with Chiari II) aged 4 to 58 years (of them 12 males). Hydrocephalus was diagnosed in 4 examined patients and myelosyringosis was diagnosed in 6 patients. Transcranial Doppler sonography was used to record the venous blood flow in the tentorial sinus of the brain while changing body position on the fracture table from +90° to -30°. There is significant CVOR abnormality in most patients with Chiari malformation (more than 90%), which is characterized by either increased CVOR (sometimes 5-6-fold compared to the upper normal level (considerable hyperreactivity) or complete absence of any changes during the orthostatic load (areactivity). Before surgical treatment, CVOR of patients with Chiari malformation is often characterized by areactivity, as well as a moderate or significant hyperreactivity. After surgical treatment (decompression of the foramen magnum), patients with Chiari malformation demonstrate significant normalization of the craniovertebral volumetric ratios and CVOR if often characterized by normoreactivity (in 63%) or, more rarely, moderate hyperreactivity. The rate of venous blood flow in the tentorial sinus of the brain in patients with Chiari malformation can be increased before the surgery and normalizes after surgery. The high incidence of disturbance of CVOR (over 90%) in patients with Chiari malformation was revealed. After surgical treatment

Computer simulation studies in fluid and calcium regulation and orthostatic intolerance

NASA Technical Reports Server (NTRS)

1985-01-01

The systems analysis approach to physiological research uses mathematical models and computer simulation. Major areas of concern during prolonged space flight discussed include fluid and blood volume regulation; cardiovascular response during shuttle reentry; countermeasures for orthostatic intolerance; and calcium regulation and bone atrophy. Potential contributions of physiologic math models to future flight experiments are examined.

Orthostatic Tremor: An Update on a Rare Entity

PubMed Central

Benito-León, Julián; Domingo-Santos, Ángela

2016-01-01

Background Orthostatic tremor (OT) remains among the most intriguing and poorly understood of movement disorders. Compared to Parkinson’s disease or even essential tremor, there are very few articles addressing more basic science issues. In this review, we will discuss the findings of main case series on OT, including data on etiology, pathophysiology, diagnostic approach, treatment strategies, and outcome. Methods Data for this review were identified by searching PUBMED (January 1966 to August 2016) for the terms “orthostatic tremor” or “shaky leg syndrome,” which yielded 219 entries. We did not exclude papers on the basis of language, country, or publication date. The electronic database searches were supplemented by articles in the authors’ files that pertained to this topic. Results Owing to its rarity, the current understanding of OT is limited and is mostly based on small case series or case reports. Despite this, a growing body of evidence indicates that OT might be a progressive condition that is clinically heterogeneous (primary vs. secondary cases) with a broader spectrum of clinical features, mainly cerebellar signs, and possible cognitive impairment and personality disturbances. Along with this, advanced neuroimaging techniques are now demonstrating distinct anatomical and functional changes, some of which are consistent with neuronal loss. Discussion OT might be a family of diseases, unified by the presence of leg tremor, but further characterized by etiological and clinical heterogeneity. More work is needed to understand the pathogenesis of this condition. PMID:27713855

Hypotensive Anesthesia versus Normotensive Anesthesia during Major Maxillofacial Surgery: A Review of the Literature

PubMed Central

Yoav, Leiser; Abu el-Naaj, Imad

2015-01-01

Steady blood pressure within normal limits during surgery is one of the markers of the ideal and skillful anesthesia. Yet, reduced blood pressure is advantageous in some settings because it can contribute to a reduction in overall blood loss and improve the surgical field conditions. Controlled hypotension during anesthesia or hypotensive anesthesia is often used in major maxillofacial operations. Since hypotensive anesthesia carries the risk of hypoperfusion to important organs and tissues, mainly the brain, heart, and kidneys, it cannot be applied safely in all patients. In this paper we review the medical literature regarding hypotensive anesthesia during major maxillofacial surgery, the means to achieve it, and the risks and benefits of this technique, in comparison to normotensive anesthesia. PMID:25811042

Cerebral blood flow velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope

NASA Technical Reports Server (NTRS)

Dan, Dan; Hoag, Jeffrey B.; Ellenbogen, Kenneth A.; Wood, Mark A.; Eckberg, Dwain L.; Gilligan, David M.

2002-01-01

OBJECTIVES: We studied hemodynamic changes leading to orthostatic vasovagal presyncope to determine whether changes of cerebral artery blood flow velocity precede or follow reductions of arterial pressure. BACKGROUND: Some evidence suggests that disordered cerebral autoregulation contributes to the occurrence of orthostatic vasovagal syncope. We studied cerebral hemodynamics with transcranial Doppler recordings, and we closely examined the temporal sequence of changes of cerebral artery blood flow velocity and systemic arterial pressure in 15 patients who did or did not faint during passive 70 degrees head-up tilt. METHODS: We recorded photoplethysmographic arterial pressure, RR intervals (electrocardiogram) and middle cerebral artery blood flow velocities (mean, total, mean/RR interval; Gosling's pulsatility index; and cerebrovascular resistance [mean cerebral velocity/mean arterial pressure, MAP]). RESULTS: Eight men developed presyncope, and six men and one woman did not. Presyncopal patients reported light-headedness, diaphoresis, or a sensation of fatigue 155 s (range: 25 to 414 s) before any cerebral or systemic hemodynamic change. Average cerebral blood flow velocity (CBFV) changes (defined by an iterative linear regression algorithm) began 67 s (range: 9 to 198 s) before reductions of MAP. Cerebral and systemic hemodynamic measurements remained constant in nonsyncopal patients. CONCLUSIONS: Presyncopal symptoms and CBFV changes precede arterial pressure reductions in patients with orthostatic vasovagal syncope. Therefore, changes of cerebrovascular regulation may contribute to the occurrence of vasovagal reactions.

Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.

PubMed

Campolo, Jonica; De Maria, Renata; Cozzi, Lorena; Parolini, Marina; Bernardi, Stefano; Proserpio, Paola; Nobili, Lino; Gelosa, Giorgio; Piccolo, Immacolata; Agostoni, Elio C; Trivella, Maria G; Marraccini, Paolo

2016-11-15

We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD. We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin). Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016). Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

PubMed

Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

2013-10-01

High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

Using Concurrent Cardiovascular Information to Augment Survival Time Data for Evaluating Orthostatic Tilt Test Performance

NASA Technical Reports Server (NTRS)

Feiveson, Alan H.; Fiedler, James; Lee, Stuart M. C.; Koslovsky, Matthew D.; Stenger, Michael B.; Platts, Steven H.

2018-01-01

Head-up tilt (HUT) tests often are used in research to measure orthostatic intolerance (OI) (inability to appropriately control blood pressure while upright) in clinical populations and otherwise healthy individuals after interventions. Post-space flight orthostatic intolerance is a well-known phenomenon, and countermeasures to its development has been an active area of research at NASA. In the NASA HUT protocol, subjects lie horizontally on an automatic tilt table for baseline measurements before being raised to 80deg head-up tilt for a defined period of time or until signs or symptoms of presyncope ensues (light-headedness, nausea, dizziness, sweating, weakness or fainting). Multiple measures are collected to evaluate the cardiovascular system's ability to respond appropriately to the orthostatic challenge. However if the intended duration of the HUT is short, the ability to detect changes in OI due to an intervention or its prevention by a countermeasure may be limited by a small number of failures to permit comparisons based on survival time alone. Thus, the time-trajectory of the cardiovascular data becomes an important additional source of information. In particular, we will show how various measures of trajectory variability can effectively augment survival analysis for the assessment of OI in a joint model when high censoring rates are present.

Student Engagement for College Students with the Hidden Disability of Orthostatic Intolerance

ERIC Educational Resources Information Center

Karabin, Beverly Lynn

2010-01-01

This study described the factors that contribute to engagement patterns of college students with the hidden health-related disability of orthostatic intolerance. Specifically, it used a qualitative methodology and collective-case study design to explore the categories of campus physical, institutional, academic and social engagement from a student…

Outcomes following trauma laparotomy for hypotensive trauma patients: a UK military and civilian perspective.

PubMed

Marsden, Max; Carden, Rich; Navaratne, Lalin; Smith, Iain M; Penn-Barwell, Jowan G; Kraven, Luke M; Brohi, Karim; Tai, Nigel R M; Bowley, Douglas M

2018-05-25

The management of trauma patients has changed radically in the last decade and studies have shown overall improvements in survival. However, reduction in mortality for the many may obscure a lack of progress in some high-risk patients. We sought to examine the outcomes for hypotensive patients requiring laparotomy in UK military and civilian cohorts. We undertook a review of two prospectively maintained trauma databases; the UK Joint Theatre Trauma Registry (JTTR) for the military cohort (4th February 2003 to 21st September 2014), and the trauma registry of the Royal London Hospital MTC (1st January 2012 to 1st January 2017) for civilian patients. Adults undergoing trauma laparotomy within 90 minutes of arrival at the Emergency Department (ED) were included. Hypotension was present on arrival at the ED in 155/761 (20.4%) military patients. Mortality was higher in hypotensive casualties 25.8% vs 9.7% normotensive casualties (p<0.001). Hypotension was present on arrival at the ED in 63/176 (35.7%) civilian patients. Mortality was higher in hypotensive patients 47.6% vs 12.4% normotensive patients (p<0.001). In both cohorts of hypotensive patients neither the average injury severity, the prehospital time, the ED arrival SBP, nor mortality rate changed significantly during the study period. Despite improvements in survival after trauma for patients overall, the mortality for patients undergoing laparotomy who arrive at the Emergency Department with hypotension has not changed and appears stubbornly resistant to all efforts. Specific enquiry and research should continue to be directed at this high-risk group of patients. IV; Observational Cohort Study.

High Intensity Resistive and Rowing Exercise Countermeasures Do Not Prevent Orthostatic Intolerance Following 70 Days of Bed Rest

NASA Technical Reports Server (NTRS)

Lee, Stuart M. C.; Stenger, Michael B.; Laurie, Steven S.; Ploutz-Snyder, Lori L.; Platts, Steven H.

2015-01-01

More than 60% of US astronauts participating in Mir and early International Space Station missions (greater than 5 months) were unable to complete a 10-min 80 deg head-up tilt test on landing day. This high incidence of post-spaceflight orthostatic intolerance may be related to limitations of the inflight exercise hardware that prevented high intensity training. PURPOSE: This study sought to determine if a countermeasure program that included intense lower-body resistive and rowing exercises designed to prevent cardiovascular and musculoskeletal deconditioning during 70 days of 6 deg head-down tilt bed rest (BR), a spaceflight analog, also would protect against post- BR orthostatic intolerance. METHODS: Sixteen males participated in this study and performed no exercise (Control, n=10) or performed an intense supine exercise protocol with resistive and aerobic components (Exercise, n=6). On 3 days/week, exercise subjects performed lower body resistive exercise and a 30-min continuous bout of rowing (greater than or equal to 75% max heart rate). On 3 other days/week, subjects performed only high-intensity, interval-style rowing. Orthostatic intolerance was assessed using a 15-min 80 deg head-up tilt test performed 2 days (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using a carbon monoxide rebreathing technique on BR-3 and before rising on the first recovery day (BR+0). RESULTS: Following 70 days of BR, tilt tolerance time decreased significantly in both the Control (BR-2: 15.0 +/- 0.0, BR70: 9.9 +/- 4.6 min, mean +/- SD) and Exercise (BR-2: 12.2 +/- 4.7, BR70: 4.9 +/- 1.9 min) subjects, but the decreased tilt tolerance time was not different between groups (Control: -34 +/- 31, Exercise: -56 +/- 16%). Plasma volume also decreased (Control: -0.56 +/- 0.40, Exercise: -0.48 +/- 0.33 L) from pre to post-BR, with no differences between groups (Control: -18 +/- 11%, Exerciser: -15 +/-1 0%). CONCLUSIONS: These findings confirm previous reports

Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial.

PubMed

Khan, Nadia A; Campbell, Norman R; Frost, Shaun D; Gilbert, Ken; Michota, Frank A; Usmani, Ali; Seal, Doug; Ghali, William A

2010-11-01

There is growing concern regarding the safety of blood pressure-lowering medications administered during the perioperative period. Whether loop diuretics also induce intraoperative hypotension is uncertain. Our objective was to compare the effects of continuing or withholding furosemide on the day of noncardiac elective surgery on intraoperative hypotension among chronic users of furosemide. A double blind, randomized, placebo controlled trial was conducted at 3 North American university centers between September 2000 and December 2006. Participants were randomly assigned in a 1:1 ratio to receive either furosemide or placebo on the day of surgery. The primary outcome was risk of developing intraoperative hypotension. A priori secondary outcomes included risk of heart failure; composite cardiovascular event (myocardial infarction, arrhythmia, stroke or transient ischemic attack, or death); and change in renal function and electrolytes. Of the 212 patients enrolled, 193 patients underwent surgery. There was no significant difference in risk of developing intraoperative hypotension between the furosemide (49%) and placebo (51.9%) groups (relative risk [RR], 0.95; 95% confidence interval [CI], 0.72-1.24; P = .78). The intraoperative administration of vasopressors and fluids were similar between both groups. The risk of developing postoperative cardiovascular events was not significantly different between those randomized to furosemide (4.8%) or placebo (2.8%) (RR, 1.73; 95% CI, 0.42-7.06; P = .49). There was no significant difference in renal function or electrolytes between the 2 groups. Among elective, noncardiac surgeries in patients chronically treated with furosemide, the administration of furosemide on the day of surgery did not significantly increase the risk for intraoperative hypotension. Copyright © 2010 Elsevier Inc. All rights reserved.

Permissive hypotension in bleeding trauma patients: helpful or not and when?

PubMed

Gourgiotis, Stavros; Gemenetzis, George; Kocher, Hemant M; Aloizos, Stavros; Salemis, Nikolaos S; Grammenos, Stylianos

2013-12-01

Severity of hemorrhage and rate of bleeding are fundamental factors in the outcomes of trauma. Intravenous administration of fluid is the basic treatment to maintain blood pressure until bleeding is controlled. The main guideline, used almost worldwide, Advanced Trauma Life Support, established by the American College of Surgeons in 1976, calls for aggressive administration of intravenous fluids, primarily crystalloid solutions. Several other guidelines, such as Prehospital Trauma Life Support, Trauma Evaluation and Management, and Advanced Trauma Operative Management, are applied according to a patient's current condition. However, the ideal strategy remains unclear. With permissive hypotension, also known as hypotensive resuscitation, fluid administration is less aggressive. The available models of permissive hypotension are based on hypotheses in hypovolemic physiology and restricted clinical trials in animals. Before these models can be used in patients, randomized, controlled clinical trials are necessary.

[Prophylaxis and treatment of arterial hypotension during caesarean with spinal anaesthesia].

PubMed

Arias, J; Lacassie, H J

2013-11-01

Caesarean section is one of the most common surgical procedures worldwide. Arterial hypotension is the most prevalent adverse effect after spinal anaesthesia. Various methods have been used to prevent or treat hypotension. Since there is no treatment 100% effective by itself, a multimodal management is required to achieve an optimum balance and avoidance of hemodynamic imbalance. Strategies to avoid this side effect are analyzed on the basis of the best evidence available so far, summarized as mechanical factors, anesthetics, fluids and vasopressors. After spinal anaesthesia for caesarean section, the best strategy available for prevention of hypotension appears to be the combination of crystalloids along with an alpha 1 agonist vasopressor. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Defining hypotension in moderate to severely injured trauma patients: raising the bar for the elderly.

PubMed

Edwards, Meghan; Ley, Eric; Mirocha, James; Hadjibashi, Anoushiravan Amini; Margulies, Daniel R; Salim, Ali

2010-10-01

Hypotension, defined as systolic blood pressure less than 90 mm Hg, is recognized as a sign of hemorrhagic shock and is a validated prognostic indicator. The definition of hypotension, particularly in the elderly population, deserves attention. We hypothesized that the systolic blood pressure associated with increased mortality resulting from hemorrhagic shock increases with increasing age. The Los Angeles County Trauma Database was queried for all moderate to severely injured patients without major head injuries admitted between 1998 and 2005. Several fit statistic analyses were performed for each systolic blood pressure from 50 to 180 mm Hg to identify the model that most accurately defined hypotension for three age groups. The optimal definition of hypotension for each group was determined from the best fit model. A total of 24,438 patients were analyzed. The optimal definition of hypotension was systolic blood pressure of 100 mm Hg for patients 20 to 49 years, 120 mm Hg for patients 50 to 69 years, and 140 mm Hg for patients 70 years and older. The optimal systolic blood pressure for improved mortality in hemorrhagic shock increases significantly with increasing age. Elderly trauma patients without major head injuries should be considered hypotensive for systolic blood pressure less than 140 mm Hg.

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

Influence of mianserin on the activity of some hypotensive drugs in spontaneously hypertensive rats.

PubMed

Górska, Dorota; Andrzejczak, Dariusz

2003-01-01

Mianserin might be an alternative drug in patients with depression accompanied by hypertension because of its effectiveness and lack of side effects in the circulatory system. However, a few studies reported in literature show influence of the drug on blood pressure. We investigate interactions between mianserin and commonly used hypotensive drugs (propranolol, enalapril and prazosin) in spontaneously hypertensive rats (SHR). The experiments were performed in two experimental designs: a single administration of both mianserin and a hypotensive drug, and repeated administration of mianserin with a single administration of a hypotensive drug. Arterial blood pressure was measured by bloodless method with manometer made by LETICA. A single administration of mianserin caused a statistically significant decrease in systolic, diastolic and mean blood pressure in the 60th minute of observation and intensified hypotensive effect of prazosin. However, long-term administration of mianserin in SHR rats had no significant influence on arterial blood pressure. Chronic and single administration of mianserin with propranolol or enalapril did not influence the circulatory system. A long-term administration of mianserin intensified the hypotensive effect of prazosin. This interaction might suggest possibility of dangerous complications in the treatment of humans with this drug combination.

Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients.

PubMed

Sullivan, D H; Carter, W J; Warr, W R; Williams, L H

1998-05-01

The objective of this study was to examine the relationship between serum IGF-I concentration and the incidence of side effects of therapy with recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-I (rhIGF-I). Thirteen high-risk, undernourished elderly males were started on a 15-day course of rhGH and rhIGF-I by subcutaneous injection. The dose of rhGH was held constant at .0125 mg/kg/day, whereas the dose of rhIGF-I was increased in a stepwise fashion from 10 micrograms/kg to the targeted dose of 40 micrograms/kg twice a day. Nine subjects completed the protocol and reached the full target dose of both hormones. Fluid retention, gynecomastia, and orthostatic hypotension were the most common complications. The hormone injections increased the serum concentration of IGF-I (from 72.7 +/- 40.9 to 483.7 +/- 251.4 eta g/ml, p = .001) and IGFBP-3 (from 1.82 +/- 0.66 to 2.72 +/- 1.18 mg/L, p = .012), and decreased serum albumin (from 34.3 +/- 5.5 to 31.4 +/- 4.6 g/L, p = .009). The magnitude of the initial increase in the serum IGF-I concentration was a powerful risk factor for severe orthostatic hypotension, diffuse myalgias, and drug-induced hepatitis. There was no association between the serum IGF-I concentration and fluid retention or gynecomastia. Treatment of the undernourished frail elderly with the anabolic agents rhGH and rhIGF-I at the specified dosages may produce undesirable side effects including fluid retention, gynecomastia, and orthostatic hypotension. Although these agents hold therapeutic promise, they must be used with caution in this high-risk population.

Marked exacerbation of orthostatic intolerance after long- vs. short-duration spaceflight in veteran astronauts.

PubMed

Meck, J V; Reyes, C J; Perez, S A; Goldberger, A L; Ziegler, M G

2001-01-01

The incidence of postflight orthostatic intolerance after short-duration spaceflight is about 20%. However, the incidence after long-duration spaceflight was unknown. The purpose of this study was to test the hypothesis that orthostatic intolerance is more severe after long-duration than after short-duration flight. We performed tilt tests on six astronauts before and after long-duration (129-190 days) spaceflights and compared these data with data obtained during stand tests before and after previous short-duration missions. Five of the six astronauts studied became presyncopal during tilt testing after long-duration flights. Only one had become presyncopal during stand testing after short-duration flights. We also compared the long-duration flight tilt test data to tilt test data from 20 different astronauts who flew on the short-duration Shuttle missions that delivered and recovered the astronauts to and from the Mir Space Station. Five of these 20 astronauts became presyncopal on landing day. Heart rate responses to tilt were no different between astronauts on long-duration flights and astronauts on short-duration flights, but long-duration subjects had lower stroke volumes and cardiac outputs than short-duration presyncopal subjects, suggesting a possible decrease in cardiac contractile function. One subject had subnormal norepinephrine release with upright posture after the long flight but not after the short flight. Plasma volume losses were not greater after long flights. Long-duration spaceflight markedly increases orthostatic intolerance, probably with multiple contributing factors.

Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

PubMed

Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

2007-04-01

The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

Autoregulation of cerebral blood circulation under orthostatic tests

NASA Technical Reports Server (NTRS)

Gayevyy, M. D.; Maltsev, V. G.; Pogorelyy, V. E.

1980-01-01

Autoregulation of cerebral blood flow (ACBF) under orthostatic tests (OT) was estimated in acute experiments on rabbits and cats under local anesthesia according to changes of perfusion pressure (PP) in carotid arteries, cerebral blood flow, pressure in the venous system of the brain, and resistance of cerebral vessels. The OT were conducted by turning a special table with the animal fastened to it from a horizontal to a vertical (head up or head down) position at 40 to 80 deg. In most experiments ACBF correlated with the changes of PP. Different variations of ACBF and its possible mechanisms are discussed.

Autogenic-feedback training: A countermeasure for orthostatic intolerance

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Toscano, William B.; Kamiya, Joe; Miller, Neal E.; Pickering, Thomas G.

1991-01-01

NASA has identified cardiovascular deconditioning as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder and the resulting orthostatic intolerance experienced by crewmembers upon their return to the 1g norm of Earth. The present study was designed to examine the feasibility of training human subjects to control their own cardiovascular responses to gravitational stimulation (i.e., a tilt table). Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), we would determine if subjects could learn to increase their own blood pressure voluntarily.

Superoxide and Nitric Oxide Mechanisms in Traumatic Brain Injury and Hemorrhagic Hypotension.

DTIC Science & Technology

1999-12-01

DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 Words) Traumatic brain injury (TBI) renders the brain vulnerable to secondary ischemia and poor outcome...cerebral blood flow (CBF) and renders the brain vulnerable to secondary ischemia. There is clinical evidence that hypotension contributes to poor...without TBI. These data indicate that even moderate TBI renders the brain sensitive to ischemic injury during relative mild levels of hypotension that

Does mental arithmetic before head up tilt have an effect on the orthostatic cardiovascular and hormonal responses?

NASA Astrophysics Data System (ADS)

Goswami, Nandu; Lackner, Helmut Karl; Papousek, Ilona; Montani, Jean-Pierre; Jezova, Daniela; Hinghofer-Szalkay, Helmut G.

2011-05-01

Passive head up tilt (HUT) and mental arithmetic (MA) are commonly used for providing mental and orthostatic challenges, respectively. In animal experiments, even a single exposure to a stressor has been shown to modify the response to subsequent stress stimulus. We investigated whether MA applied before HUT elicits synergistic responses in orthostatic heart rate (HR), cardiac output (CO), heart rate variability and arterial blood pressure. The 15 healthy young males were subjected to two randomized protocols: (a) HUT and (b) HUT preceded by MA, with sessions randomized and ≥2 weeks apart. Beat to beat continuous hemodynamic variables were measured and saliva samples taken for hormonal assay. HUT alone increased HR from 59±7 (baseline) to 80±10 bpm (mean±SD) and mean blood pressure (MBP) from 88±10 to 91±14 mmHg. HUT results after MA were not different from those with HUT alone. The activity of alpha amylase showed differences during the experiments irrespective of the protocols. We conclude that mental challenge does not affect orthostatic cardiovascular responses when applied before; the timing of mental loading seems to be critical if it is intended to alter cardiovascular responses to upright standing.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

PubMed

Colì, Luigi; La Manna, Gaetano; Comai, Giorgia; Ursino, Mauro; Ricci, Davide; Piccari, Matteo; Locatelli, Francesco; Di Filippo, Salvatore; Cristinelli, Luciano; Bacchi, Massimo; Balducci, Alessandro; Aucella, Filippo; Panichi, Vincenzo; Ferrandello, Francesco Paolo; Tarchini, Renzo; Lambertini, Domenica; Mura, Carlo; Marinangeli, Giancarlo; Di Loreto, Ermanno; Quarello, Francesco; Forneris, Giacomo; Tancredi, Maurizio; Morosetti, Massimo; Palombo, Giuditta; Di Luca, Marina; Martello, Mauro; Emiliani, Giuseppe; Bellazzi, Roberto; Stefoni, Sergio

2011-07-01

Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. A noncontrolled (single arm), multicenter, prospective, clinical trial. 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. A noncontrolled (single arm) study, no crossover from AASD to standard treatment. This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

1988-01-01

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

Multiple System Atrophy with Orthostatic Hypotension (Shy-Drager Syndrome)

MedlinePlus

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Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India.

PubMed

Prabhakaran, Vasudevan; Drevets, Douglas A; Ramajayam, Govindan; Manoj, Josephine J; Anderson, Michael P; Hanas, Jay S; Rajshekhar, Vedantam; Oommen, Anna; Carabin, Hélène

2017-06-01

Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches. Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications. Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to

Cardiovascular aspects of Parkinson disease.

PubMed

Goldstein, D S

2006-01-01

This chapter provides an update about cardiovascular aspects of Parkinson disease (PD), with the following topics: (1) Orthostatic hypotension (OH) as an early finding in PD; (2) neurocirculatory abnormalities in PD + OH independent of levodopa treatment; (3) cardiac and extracardiac noradrenergic denervation in PD + OH; (4) progressive loss of cardiac sympathetic innervation in PD without OH.

Baroreflex-Mediated Heart Rate and Vascular Resistance Responses 24 h after Maximal Exercise

DTIC Science & Technology

2003-01-01

of normal physiological function in bedridden patients and astronauts. The implication for failure of CVP and plasma volume to return to baseline... FUNCTION , BLOOD PRES- SURE, CENTRAL VENOUS PRESSURE, PHENYLEPHRINE, NECK PRESSURE, LOWER BODY NEGATIVE PRESSURE, COUNTERMEASURES Increased incidence of...orthostatic hypotension and intol-erance in humans is associated with vascular hypovole-mia and attenuated cardiovascular reflex functions

Effects of prior physical exertion on tolerance to hypoxia, orthostatic stress, and physical fatigue.

DOT National Transportation Integrated Search

1982-03-01

Ten healthy men, 20-35 years old, were tested for tolerance to hypoxia, orthostatic stress, and physical fatigue after a period of rest, and, on another occasion, after a period of physical exertion. Exertion consisted of four 10-min periods of pedal...

Custom Gradient Compression Stockings May Prevent Orthostatic Intolerance in Astronauts After Space Flight

NASA Technical Reports Server (NTRS)

Stenger, Michael B.; Lee, Stuart M. C.; Westby, Christian M.; Platts, Steven H.

2010-01-01

Orthostatic intolerance after space flight is still an issue for astronauts as no in-flight countermeasure has been 100% effective. NASA astronauts currently wear an inflatable anti-gravity suit (AGS) during re-entry, but this device is uncomfortable and loses effectiveness upon egress from the Shuttle. We recently determined that thigh-high, gradient compression stockings were comfortable and effective after space flight, though to a lesser degree than the AGS. We also recently showed that addition of splanchnic compression to this thigh-high compression stocking paradigm improved orthostatic tolerance to a level similar to the AGS, in a ground based model. Purpose: The purpose of this study was to evaluate a new, three-piece breast-high gradient compression garment as a countermeasure to post-space flight orthostatic intolerance. Methods: Eight U.S. astronauts have volunteered for this experiment and were individually fitted for a three-piece, breast-high compression garment to provide 55 mmHg compression at the ankle which decreased to approximately 20 mmHg at the top of the leg and provides 15 mmHg over the abdomen. Orthostatic testing occurred 30 days pre-flight (w/o garment) and 2 hours after flight (w/ garment) on landing day. Blood pressure (BP), Heart Rate (HR) and Stroke Volume (SV) were acquired for 2 minutes while the subject lay prone and then for 3.5 minutes after the subject stands up. To date, two astronauts have completed pre- and post-space flight testing. Data are mean SD. Results: BP [pre (prone to stand): 137+/-1.6 to 129+/-2.5; post: 130+/-2.4 to 122+/-1.6 mmHg] and SV [pre (prone to stand): 61+/-1.6 to 38+/-0.2; post: 58+/-6.4 to 37+/-6.0 ml] decreased with standing, but no differences were seen post-flight w/ compression garments compared to pre-flight w/o garments. HR [pre (prone to stand): 66+/-1.6 to 74+/-3.0, post: 67+/-5.6 to 78+/-6.8 bpm] increased with standing, but no differences were seen pre- to post-flight. Conclusion: After space

Orthostatically Induced Panic Attacks among Cambodian Refugees: Flashbacks, Catastrophic Cognitions, and Associated Psychopathology

ERIC Educational Resources Information Center

Hinton, Devon E.; Pollack, Mark H.; Pich, Vuth; Fama, Jeanne M.; Barlow, David H.

2005-01-01

Consecutive Cambodian refugees (N = 100) attending a psychiatric clinic were assessed for the presence and severity of current orthostatic panic (OP), which is defined as panic triggered by standing up. The patients with current OP (n = 36) had significantly greater psychopathology than patients without current OP. During OP, trauma associations…

More hypotension in patients taking antihypertensives preoperatively during shoulder surgery in the beach chair position.

PubMed

Trentman, Terrence L; Fassett, Sharon L; Thomas, Justin K; Noble, Brie N; Renfree, Kevin J; Hattrup, Steven J

2011-11-01

Hypotension is common in patients undergoing surgery in the sitting position under general anesthesia, and the risk may be exacerbated by the use of antihypertensive drugs taken preoperatively. The purpose of this study was to compare hypotensive episodes in patients taking antihypertensive medications with normotensive patients during shoulder surgery in the beach chair position. Medical records of all patients undergoing shoulder arthroscopy during a 44-month period were reviewed retrospectively. The primary endpoint was the number of moderate hypotensive episodes (systolic blood pressure ≤ 85 mmHg) during the intraoperative period. Secondary endpoints included the frequency of vasopressor administration, total dose of vasopressors, and fluid administered. Values are expressed as mean (standard deviation). Of 384 patients who underwent shoulder surgery, 185 patients were taking no antihypertensive medication, and 199 were on at least one antihypertensive drug. The antihypertensive medication group had more intraoperative hypotensive episodes [1.7 (2.2) vs 1.2 (1.8); P = 0.01] and vasopressor administrations. Total dose of vasopressors and volume of fluids administered were similar between groups. The timing of the administration of angiotensin-converting enzyme inhibitors and of angiotensin receptor antagonists (≤ 10 hr vs > 10 hr before surgery) had no impact on intraoperative hypotension. Preoperative use of antihypertensive medication was associated with an increased incidence of intraoperative hypotension. Compared with normotensive patients, patients taking antihypertensive drugs preoperatively are expected to require vasopressors more often to maintain normal blood pressure.

Orthostatic Intolerance After ISS and Space Shuttle Missions.

PubMed

Lee, Stuart M C; Feiveson, Alan H; Stein, Sydney; Stenger, Michael B; Platts, Steven H

2015-12-01

Cardiovascular deconditioning apparently progresses with flight duration, resulting in a greater incidence of orthostatic intolerance following long-duration missions. Therefore, we anticipated that the proportion of astronauts who could not complete an orthostatic tilt test (OTT) would be higher on landing day and the number of days to recover greater after International Space Station (ISS) than after Space Shuttle missions. There were 20 ISS and 65 Shuttle astronauts who participated in 10-min 80° head-up tilt tests 10 d before launch, on landing day (R+0), and 3 d after landing (R+3). Fisher's Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the OTT. Cox regression was used to identify cardiovascular parameters associated with OTT completion and mixed model analysis was used to compare the change and recovery rates between groups. The proportion of astronauts who completed the OTT on R+0 (2 of 6) was less in ISS than in Shuttle astronauts (52 of 65). On R+3, 13 of 15 and 19 of 19 of the ISS and Shuttle astronauts, respectively, completed the OTT. An index comprised of stroke volume and diastolic blood pressure provided a good prediction of OTT completion and was altered by spaceflight similarly for both astronaut groups, but recovery was slower in ISS than in Shuttle astronauts. The proportion of ISS astronauts who could not complete the OTT on R+0 was greater and the recovery rate slower after ISS compared to Shuttle missions. Thus, mission planners and crew surgeons should anticipate the need to tailor scheduled activities and level of medical support to accommodate protracted recovery after long-duration microgravity exposures.

[How can we improve symptomatic hypotension in hemodialysis patients: cold dialysis vs isothermic dialysis].

PubMed

Ramos, R; Soto, C; Mestres, R; Jara, J; Zequera, H; Merello, J I; Moreso, F

2007-01-01

Symptomatic hypotension is the most frequent acute complication affecting patients during chronic hemodialysis treatment sessions. Many reports have demonstrated that the use of cool dialysate has a protective effect on blood pressure during hemodialysis treatments. In the present study, we investigated whether preventing the hyperthermic response had favourable effects on hemodynamic stability during the hemodialysis procedure while affording good tolerance to patients. We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients in our center. Patients were eligible for the study if they had symptomatic hypotensive episodes (> 3/12session/ month) during the screening phase. The study was designed with two phases for the same selected patients and two treatment arms, each phase lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36 masculineC for 12 sessions (cold dialysis) and in the second phase we used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature unchanged (isothermic dialysis). Nine HD patients were enrolled and completed the study. During the screening phase the mean ultrafiltration was 4 1% of dry weight, and blood pressure decreased from 9916 to 8016 mm Hg (p<0.001). In 5.01.7 sessions of 12 treatments were complicated by hypotension. In the first and second phase we observed a decrease of complicated treatments with symptomatic hypotension (5.01.7 versus 2.71.6 y 2.81.7; p<0.01). Both procedures: Cold dialysis and Isothermic dialysis was well tolerated by patients. Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients.

Responses of women to orthostatic and exercise stresses

NASA Technical Reports Server (NTRS)

Hoffler, G. W.; Jackson, M. M.; Johnson, R. L.; Baker, J. T.; Tatro, D.

1990-01-01

The results are presented from a special physiological study of women at the Johnson Space Center in 1976 to 1977. Its purpose was to establish a large (98 subjects) database from normal working women. The data sets are medical historical, clinical, anthropometric, and stress response statistics useful for establishing medical criteria for selecting women astronauts. Stressors were lower body negative pressure and static standing (both orthostatic) and treadmill exercise (ergometric). Data shown are original individual values with analyses and subsets, and statistical summaries and correlations relating to human responses to microgravity. Similarities appear between the characteristics of women in this study and those of women astronauts currently flying in Shuttle crews.

Hypotension and Bradycardia Caused by the Inadvertent Ingestion of Rhododendron japonicum.

PubMed

Koda, Ryo; Honma, Miho; Suzuki, Kazuo; Kasai, Akio; Takeda, Tetsuro; Narita, Ichiei; Yoshida, Kazukiyo

2016-01-01

A 61-year-old man was transferred to our hospital with the complaints of dizziness, severe nausea and abdominal discomfort after consuming approximately 50 g of the flowers of Rhododendron japonicum. On admission, hypotension and sinus bradycardia were evident. Symptoms including hypotension and bradycardia completely recovered within 12 hours following normal saline infusion and intravenous atropine. The ingestion of certain types of Rhododendron species can cause intoxication, referred to as "mad honey poisoning", due to the action of grayanotoxins. This is the first local case of acute intoxication caused by Rhododendron japonicum.

Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Martin, David S.; Perez, Sondar A.; Ribeiro, Christine; Stenger, Michael B.; Summers, Richard; Meck, Janice V.

2008-01-01

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Epidural Spinal Cord Stimulation of Lumbosacral Networks Modulates Arterial Blood Pressure in Individuals With Spinal Cord Injury-Induced Cardiovascular Deficits.

PubMed

Aslan, Sevda C; Legg Ditterline, Bonnie E; Park, Michael C; Angeli, Claudia A; Rejc, Enrico; Chen, Yangsheng; Ovechkin, Alexander V; Krassioukov, Andrei; Harkema, Susan J

2018-01-01

Disruption of motor and autonomic pathways induced by spinal cord injury (SCI) often leads to persistent low arterial blood pressure and orthostatic intolerance. Spinal cord epidural stimulation (scES) has been shown to enable independent standing and voluntary movement in individuals with clinically motor complete SCI. In this study, we addressed whether scES configured to activate motor lumbosacral networks can also modulate arterial blood pressure by assessing continuous, beat-by-beat blood pressure and lower extremity electromyography during supine and standing in seven individuals with C5-T4 SCI. In three research participants with arterial hypotension, orthostatic intolerance, and low levels of circulating catecholamines (group 1), scES applied while supine and standing resulted in increased arterial blood pressure. In four research participants without evidence of arterial hypotension or orthostatic intolerance and normative circulating catecholamines (group 2), scES did not induce significant increases in arterial blood pressure. During scES, there were no significant differences in electromyographic (EMG) activity between group 1 and group 2. In group 1, during standing assisted by scES, blood pressure was maintained at 119/72 ± 7/14 mmHg (mean ± SD) compared with 70/45 ± 5/7 mmHg without scES. In group 2 there were no arterial blood pressure changes during standing with or without scES. These findings demonstrate that scES configured to facilitate motor function can acutely increase arterial blood pressure in individuals with SCI-induced cardiovascular deficits.

Postural headache in marfan syndrome associated with spinal cysts and liquor hypotension.

PubMed

Voermans, N C; Dijk, K G J van; Bos, M M; Geus-Oei, L-F de; Verrips, A; Lindert, E J van

2009-08-01

We here report a 13-year-old Marfan patient who suffered from severe, medication-resistant, intermittent headache, which was provoked when getting into an upright position and immediately relieved by lying down or after intravenous rehydration. The postural benefit and the sudden relief after intravenous hydration suggested (intermittent) intracranial hypotension, although a normal opening pressure on lumbar punction was observed and no cerebrospinal fluid (CSF) leakage was identified. Imaging studies revealed severe dural ectasia at lumbosacral level, and two intradural cysts and two extradural presacral cysts were detected. Most likely, altered hydrodynamics in intra- and extracranial spinal meningeal cysts caused intermittent CSF hypotension above these cysts, resulting in intermittent intracranial hypotension. Surgical marsupialisation of the intradural cysts proved to be effective. This resulted in a significant reduction of the headache during the clinical follow-up of eight years. Georg Thieme Verlag KG Stuttgart New York.

Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Sather, T. M.

2000-01-01

Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.

Anesthesia information management system-based near real-time decision support to manage intraoperative hypotension and hypertension.

PubMed

Nair, Bala G; Horibe, Mayumi; Newman, Shu-Fang; Wu, Wei-Ying; Peterson, Gene N; Schwid, Howard A

2014-01-01

Intraoperative hypotension and hypertension are associated with adverse clinical outcomes and morbidity. Clinical decision support mediated through an anesthesia information management system (AIMS) has been shown to improve quality of care. We hypothesized that an AIMS-based clinical decision support system could be used to improve management of intraoperative hypotension and hypertension. A near real-time AIMS-based decision support module, Smart Anesthesia Manager (SAM), was used to detect selected scenarios contributing to hypotension and hypertension. Specifically, hypotension (systolic blood pressure <80 mm Hg) with a concurrent high concentration (>1.25 minimum alveolar concentration [MAC]) of inhaled drug and hypertension (systolic blood pressure >160 mm Hg) with concurrent phenylephrine infusion were detected, and anesthesia providers were notified via "pop-up" computer screen messages. AIMS data were retrospectively analyzed to evaluate the effect of SAM notification messages on hypotensive and hypertensive episodes. For anesthetic cases 12 months before (N = 16913) and after (N = 17132) institution of SAM messages, the median duration of hypotensive episodes with concurrent high MAC decreased with notifications (Mann Whitney rank sum test, P = 0.031). However, the reduction in the median duration of hypertensive episodes with concurrent phenylephrine infusion was not significant (P = 0.47). The frequency of prolonged episodes that lasted >6 minutes (sampling period of SAM), represented in terms of the number of cases with episodes per 100 surgical cases (or percentage occurrence), declined with notifications for both hypotension with >1.25 MAC inhaled drug episodes (δ = -0.26% [confidence interval, -0.38% to -0.11%], P < 0.001) and hypertension with phenylephrine infusion episodes (δ = -0.92% [confidence interval, -1.79% to -0.04%], P = 0.035). For hypotensive events, the anesthesia providers reduced the inhaled drug concentrations to <1.25 MAC 81% of

Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.

PubMed

Stephenson, M; Wong, A; Rotella, J A; Crump, N; Kerr, F; Greene, S L

2014-06-01

Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 μg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.

Comparison of the sagittal sinus cross-sectional area between patients with multiple sclerosis, hydrocephalus, intracranial hypertension and spontaneous intracranial hypotension: a surrogate marker of venous transmural pressure?

PubMed

Bateman, Grant A; Lechner-Scott, Jeannette; Copping, Ross; Moeskops, Christopher; Yap, Swee Leong

2017-07-06

There is evidence that patients with multiple sclerosis (MS) and hydrocephalus share some common pathophysiological mechanisms. Alterations in CSF pressure are known to affect cerebral venous sinus geometry. To further explore these mechanisms, we measured the superior sagittal sinus (SSS) cross-sectional area 3 cm above the torcular using T2 images in 20 MS, 10 spontaneous intracranial hypotension (SIH), 21 hydrocephalus and 20 idiopathic intracranial hypertension (IIH) patients and compared with 20 matched controls. The SSS area was reduced by 25% in hydrocephalus (p = 0.0008), increased by 22% (p = 0.037) in SIH and unchanged in IIH compared to matched controls. In MS there was a 16% increase in SSS area (p = 0.01).The findings suggest that changes in SSS cross-sectional are common between MS and SIH patients, while in hydrocephalus and IIH these are different.

Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications.

PubMed Central

Dittmer, D. K.; Teasell, R.

1993-01-01

Prolonged bed rest and immobilization inevitably lead to complications. Such complications are much easier to prevent than to treat. Musculoskeletal complications include loss of muscle strength and endurance, contractures and soft tissue changes, disuse osteoporosis, and degenerative joint disease. Cardiovascular complications include an increased heart rate, decreased cardiac reserve, orthostatic hypotension, and venous thromboembolism. Images Figures 1-2 Figures 3-4 PMID:8324411

Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops.

PubMed

Mishra, P; Calvey, T N; Williams, N E; Murray, G R

1983-09-01

A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.

Some physiological aspects of artificial gravity. [gravitational effects on human orthostatic tolerance and physical fitness

NASA Technical Reports Server (NTRS)

Cramer, D. B.; Graybiel, A.

1973-01-01

The effects of increasing artificial gravity exposure on four aspects of physiological fitness are examined in four young men who, prior to exposure, were deconditioned with bed rest and water immersion. The four aspects of physiological fitness are orthostatic tolerance, exercise tolerance, forearm endurance, and maximum strength. Orthostatic tolerance was sharply reduced by deconditioning and was substantially improved by walking in simulated lunar gravity (1/6 g) for 2.5 hours daily for 7 days or by walking in 1/2 g and 1 g for 1 hour daily for 3 days. Exercise tolerance was also sharply reduced by deconditioning but did not significantly improve with increasing g-exposure. Walking in 1 g for 1 hour daily for 3 days raised exercise tolerance only a little above the low produced by deconditioning. Forearm endurance and maximum strength were relatively unaffected by deconditioning and subsequent g-exposure.

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

NASA Technical Reports Server (NTRS)

Lathers, Claire M.; Diamandis, Peter H.; Riddle, Jeanne M.; Mukai, Chiaki; Elton, Kay F.; Bungo, Michael W.; Charles, John B.

1991-01-01

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.

Adverse Drug Reactions for Medicines Newly Approved in Japan from 1999 to 2013: Hypertension and Hypotension.

PubMed

Nagayama, Takashi; Nishida, Minoru; Hizue, Masanori; Ogino, Yamato; Fujiyoshi, Masato

2016-04-01

In this survey, the correlation between adverse drug reactions (ADRs) in human and animal toxicities was investigated for 393 medicines which were approved in Japan from September 1999 to March 2013. ADRs were collected from each Japanese package insert. Comparable animal toxicities with ADRs were collected by thorough investigation of common technical documents. The results of this survey show that hypertension and/or hypotension were mainly observed in medicines affecting the central nervous system. Hypertension was also observed in antipyretics, analgesics, anti-inflammatory agents, vasoconstrictors and agents using antibody. Concordance between human ADRs and animal toxicities was analysed. True-positive rate for hypertension and hypotension is 0.29 and 0.52, respectively. Positive likelihood ratio and inverse negative likelihood ratio are 1.98 and 1.21, respectively, in hypertension and 1.67 and 1.44, respectively, in hypotension. Concordance between human ADRs and animal toxicities is not so high in hypertension and hypotension. Identified mechanisms as on-target for hypertension and hypotension are 29.8% and 30.5%, respectively. More than half of the causative factors of hypertension and hypotension were unable to be elucidated. Our results show that the intake of medicines is often linked to blood pressure variations that are not predicted in animal toxicity studies. Improvement of drug development processes may be necessary to provide safer medicines because current animal toxicity studies are insufficient to predict all ADRs in human beings. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Dosage variability of topical ocular hypotensive products: a densitometric assessment.

PubMed

Gaynes, Bruce I; Singa, Ramesh M; Cao, Ying

2009-02-01

To ascertain consequence of variability in drop volume obtained from multiuse topical ocular hypotensive products in terms of uniformity of product dosage. Densitometric assessment of drop volume dispensed from 2 alternative bottle positions. All except one product demonstrated a statistically significant difference in drop volume when administered at either a 45-degree or 90-degree bottle angle (Student t test, P<0.001). Product-specific drop volume ranged from a nadir of 22.36 microL to a high of 53.54 microL depending on bottle angle of administration. Deviation in drop dose was directly proportional to variability in drop volume. Variability in per drop dosage was conspicuous among products with a coefficient of variation from 1.49% to 15.91%. In accordance with drop volume, all products demonstrated a statistically significant difference in drop dose at 45-degree versus 90-degree administration angles. Drop volume was found unrelated to drop uniformity (Spearman r=0.01987 and P=0.9463). Variability and lack of uniformity in drop dosage is clearly evident among select ocular hypotensive products and is related to angle of drop administration. Erratic dosage of topical ocular hypotensive therapy may contribute in part to therapeutic failure and/or toxicity.

Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice.

PubMed

Bekker, Alex; Haile, Michael; Li, Yong-Sheng; Galoyan, Samuel; Garcia, Edwardo; Quartermain, David; Kamer, Angela; Blanck, Thomas

2009-12-01

Hypotension and a resultant decrease in cerebral blood flow have been implicated in the development of cognitive dysfunction. We tested the hypothesis that nimodipine (NIMO) administered at the onset of nitroglycerin (NTG)-induced hypotension would preserve long-term associative memory. The passive avoidance (PA) paradigm was used to assess memory retention. For PA training, latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock was automatically delivered. Latencies were recorded 48 h later for a testing trial. Ninety-six Swiss-Webster mice (30-35 g, 6-8 wk), were randomized into 6 groups 1) saline (control), 2) NTG immediately after learning, 3) NTG 3 h after learning, 4) NTG and NIMO, 5) vehicle, and 6) NIMO alone. The extent of hypotension and changes in brain tissue oxygenation (PbtO(2)) and in cerebral blood flow were studied in a separate group of animals. All groups exhibited similar training latencies (17.0 +/- 4.6 s). Mice subjected to hypotensive episodes showed a significant decrease in latency time (178 +/- 156 s) compared with those injected with saline, NTG + NIMO, or delayed NTG (580 +/- 81 s, 557 +/- 67 s, and 493 +/- 146 s, respectively). A Kruskal-Wallis 1-way analysis of variance indicated a significant difference among the 4 treatment groups (H = 15.34; P < 0.001). In a separate group of mice not subjected to behavioral studies, the same dose of NTG (n = 3) and NTG + NIMO (n = 3) caused mean arterial blood pressure to decrease from 85.9 +/- 3.8 mm Hg sem to 31.6 +/- 0.8 mm Hg sem and from 86.2 +/- 3.7 mm Hg sem to 32.6 +/- 0.2 mm Hg sem, respectively. Mean arterial blood pressure in mice treated with NIMO alone decreased from 88.1 +/- 3.8 mm Hg to 80.0 +/- 2.9 mm Hg. The intergroup difference was statistically significant (P < 0.05). PbtO(2) decreased from 51.7 +/- 4.5 mm Hg sem to 33.8 +/- 5.2 mm Hg sem in the NTG group and from 38.6 +/- 6.1 mm Hg sem to 25.4 +/- 2.0 mm Hg sem in the NTG

Mechanisms of efficacy of CBT for Cambodian refugees with PTSD: improvement in emotion regulation and orthostatic blood pressure response.

PubMed

Hinton, Devon E; Hofmann, Stefan G; Pollack, Mark H; Otto, Michael W

2009-01-01

Based on the results of a randomized controlled trial, we examined a model of the mechanisms of efficacy of culturally adapted cognitive-behavior therapy (CBT) for Cambodian refugees with pharmacology-resistant posttraumatic stress disorder (PTSD) and comordid orthostatic panic attacks (PAs). Twelve patients were in the initial treatment condition, 12 in the delayed treatment condition. The patients randomized to CBT had much greater improvement than patients in the waitlist condition on all psychometric measures and on one physiological measure-the systolic blood pressure response to orthostasis (d = 1.31)-as evaluated by repeated-measures MANOVA and planned contrasts. After receiving CBT, the Delayed Treatment Group improved on all measures, including the systolic blood pressure response to orthostasis. The CBT treatment's reduction of PTSD severity was significantly mediated by improvement in orthostatic panic and emotion regulation ability. The current study supports our model of the generation of PTSD in the Cambodian population, and suggests a key role of decreased vagal tone in the generation of orthostatic panic and PTSD in this population. It also suggests that vagal tone is involved in emotion regulation, and that both vagal tone and emotion regulation improve across treatment.

Hydrocortisone administration for the treatment of refractory hypotension in critically ill newborns.

PubMed

Baker, C F W; Barks, J D E; Engmann, C; Vazquez, D M; Neal, C R; Schumacher, R E; Bhatt-Mehta, V

2008-06-01

The purpose of this observation was to evaluate the safety and efficacy of hydrocortisone (HC) for the treatment of refractory hypotension in term and preterm infants. A secondary purpose was to determine the utility of serum cortisol concentrations in predicting the response to treatment. This is a retrospective observational study of 117 infants treated with a standardized HC protocol for refractory hypotension. Refractory hypotension was defined as a mean arterial pressure (MAP) less than the gestational age (GA) despite a total inotrope dose of 20 microg per kg per min. Baseline serum cortisol concentrations were determined prior to treatment with stress dose HC. Treatment with HC increased the MAP at 2, 6, 12 and 24 h after initiation, decreased the total inotrope dose at 6, 12 and 24 h, and was associated with resolution of oliguria. There was no correlation between the pretreatment baseline cortisol concentration and GA, birth weight or the response to treatment. The incidence of grades III to IV intraventricular hemorrhage, periventricular leukomalacia, bacterial or fungal sepsis and spontaneous intestinal perforation (SIP) after HC treatment was similar to institutional historic controls prior to institution of this standardized HC protocol. HC treatment was associated with a rapid resolution of cardiovascular compromise. The incidence of significant side effects was similar to that in previously published reports, including a comparable incidence of SIP. On the basis of our results, measuring baseline serum cortisol concentration to guide the management of refractory hypotension is unwarranted.

Natural history of idiopathic diabetes insipidus.

PubMed

Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin

2011-10-01

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.

Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor.

PubMed

Lehn, Alexander C; O'Gorman, Cullen; Olson, Sarah; Salari, Mehri

2017-01-01

Orthostatic tremor (OT) was first described in 1977. It is characterized by rapid tremor of 13-18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS). We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation. Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data.

Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor.

PubMed

Callaghan, Brid; Kosari, Samin; Pustovit, Ruslan V; Sartor, Daniela M; Ferens, Dorota; Ban, Kung; Baell, Jonathan; Nguyen, Trung V; Rivera, Leni R; Brock, James A; Furness, John B

2014-03-01

Some agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown. The effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a). Three agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84. Our results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin. © 2013 The British Pharmacological Society.

Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor

PubMed Central

Callaghan, Brid; Kosari, Samin; Pustovit, Ruslan V; Sartor, Daniela M; Ferens, Dorota; Ban, Kung; Baell, Jonathan; Nguyen, Trung V; Rivera, Leni R; Brock, James A; Furness, John B

2014-01-01

BACKGROUND AND PURPOSE Some agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown. EXPERIMENTAL APPROACH The effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a). KEY RESULTS Three agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84. CONCLUSIONS AND IMPLICATIONS Our results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin. PMID:24670149

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.

PubMed

Palma, Jose-Alberto; Kaufmann, Horacio

2018-03-01

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Vitamin D deficiency in chronic idiopathic urticaria.

PubMed

Movahedi, Masoud; Tavakol, Marzieh; Hirbod-Mobarakeh, Armin; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Tavakol, Zahra; Momenzadeh, Kaveh; Nabavi, Mohammad; Dabbaghzade, Abbas; Mosallanejad, Asieh; Rezaei, Nima

2015-04-01

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

Baroreflex dysfunction induced by microgravity: potential relevance to postflight orthostatic intolerance

NASA Technical Reports Server (NTRS)

Ertl, A. C.; Diedrich, A.; Biaggioni, I.; Robertson, D. (Principal Investigator)

2000-01-01

Microgravity imposes adaptive changes in the human body. This review focuses on the changes in baroreflex function produced by actual spaceflight, or by experimental models that simulate microgravity, e.g., bed rest. We will analyze separately studies involving baroreflexes arising from carotid sinus and aortic arch afferents ("high-pressure baroreceptors"), and cardiopulmonary afferents ("low-pressure receptors"). Studies from unrelated laboratories using different techniques have concluded that actual or simulated exposure to microgravity reduces baroreflex function arising from carotid sinus afferents ("carotic-cardiac baroreflex"). The techniques used to study the carotid-cardiac baroreflex, using neck suction and compression to simulate changes in blood pressure, have been extensively validated. In contrast, it is more difficult to selectively study aortic arch or cardiopulmonary baroreceptors. Nonetheless, studies that have examined these baroreceptors suggest that microgravity produces the opposite effect, ie, an increase in the gain of aortic arch and cardiopulmonary baroreflexes. Furthermore, most studies have focus on instantaneous changes in heart rate, which almost exclusively examines the vagal limb of the baroreflex. In comparison, there is limited information about the effect of microgravity on sympathetic function. A substantial proportion of subjects exposed to microgravity develop transient orthostatic intolerance. It has been proposed that alterations in baroreflex function play a role in the orthostatic intolerance induced by microgravity. The evidence in favor and against this hypothesis is reviewed.

Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury.

PubMed

Wecht, Jill M; Rosado-Rivera, Dwindally; Weir, Joseph P; Ivan, Adrian; Yen, Christina; Bauman, William A

2013-10-01

To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting. Open-label dose titration trial. A Veterans Administration Medical Center. Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation. Placebo on visit 1, droxidopa 100 mg on visit 2, droxidopa 200 mg on visit 3, and droxidopa 400 mg on visit 4. BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting. Seated BP was significantly elevated with 400 mg droxidopa compared with placebo and 100 mg droxidopa for 3 hours and was elevated for 2 hours compared with 200 mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400 mg. There were no significant differences in the heart rate response or AE reporting among the study visits. Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A nationwide survey of factors influencing adherence to ocular hypotensive eyedrops in Japan.

PubMed

Tsumura, Toyoaki; Kashiwagi, Kenji; Suzuki, Yasuyuki; Yoshikawa, Keiji; Suzumura, Hirotaka; Maeda, Toshine; Takeda, Ryuji; Saito, Hitomi; Araie, Makoto

2018-01-12

Few reports have investigated the status of adherence in Japan on a large scale. We aimed to investigate the status of adherence to topical glaucoma treatment and its associated factors. A nationwide survey was conducted as a prospective fashion. Participants in this survey were subjects with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic eyedrops and whose ophthalmologist considered prescribing any fixed combination of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects and their attending ophthalmologists independently completed a questionnaire by utilizing a fixed combination of ocular hypotensive eyedrops. A total of 1358 ophthalmologists from 1071 medical institutions participated in this survey. We registered 4430 subjects (2049 males and 2381 females). In total, data from 3853 subjects (87.6%) were analyzed after inclusion of subjects based on inclusion and exclusion criteria. Good adherence was defined as not forgetting instillation during the past week. Rates of good adherence reported by subjects and ophthalmologists were 72.4 and 78.5%, respectively (P < 0.0001). The consistency of adherence evaluation between subjects and ophthalmologists was moderate [kappa score 0.5025 (95% confidence interval 0.4740-0.5309)]. Significant factors associated with adherence were size of clinic, age, gender, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma. Adherence to ocular hypotensive eyedrops among Japanese subjects was relatively good. Concordance of adherence between subjects' reports and ophthalmologists' responses was moderate. Size of clinic, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge

Idiopathic ventricular tachycardia and fibrillation.

PubMed

Belhassen, B; Viskin, S

1993-06-01

Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healty patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellent.

Extended duration orbiter medical project countermeasure to reduce post space flight orthostatic intolerance (LBNP) (STS-50/USML-1)

NASA Technical Reports Server (NTRS)

Charles, John B.; Boettcher, Sheila W.

1994-01-01

During the STS-50/USML-1 mission and five other Shuttle flights, decompression of the legs and lower abdomen ('lower body negative pressure,' LBNP) was used: (1) to apply a standardized stress to the cardiovascular system, to document the loss of orthostatic function during an extended period in weightlessness, and (2) to test its efficacy as a treatment which may be used to protect astronauts from gravitationally-induced fainting during and after reentry on Space Shuttle flights. The loss of orthostatic tolerance (as determined by LBNP) occured even earlier than indicated by similar testing on Skylab (1973-1974). The treatment was shown to be effective in reversing some of the effects of extended weightlessness on the cardiovascular system for at least one day after treatment.

[The antigravity suit, chamberless type, as a means of increasing orthostatic tolerance after water immersion hypokinesis and acceleration].

PubMed

Shul'zhenko, E B; Kozlova, V G; Kurdin, K A; Iarov, A S; Plokhova, V G

1983-01-01

Orthostatic tolerance after 7-day dry immersion and head-to-feet acceleration was investigated on test subjects with and without an antigravity suit of bladderless type. With the suit on, the 20 min tilt test at 70 degrees prior to immersion induced less marked changes than without the suit. When the suit was on, cardiovascular reactions to tilt tests after immersion and acceleration improved. The maximum heart rate decreased from 135 +/- 4 to 101 +/- 5 beats/min (p less than 0.01), minimum stroke volume increased from 29 +/- 2 to 41 +/- 3 ml (p less than 0.05), and pulse pressure grew. Thus, an antigravity suit may help increase initial orthostatic tolerance and maintain it after the combined effect of simulated hypogravity and acceleration.

Perfusion index derived from a pulse oximeter can predict the incidence of hypotension during spinal anaesthesia for Caesarean delivery.

PubMed

Toyama, S; Kakumoto, M; Morioka, M; Matsuoka, K; Omatsu, H; Tagaito, Y; Numai, T; Shimoyama, M

2013-08-01

Hypotension during spinal anaesthesia for Caesarean delivery is a result of decreased vascular resistance due to sympathetic blockade and decreased cardiac output due to blood pooling in blocked areas of the body. Change in baseline peripheral vascular tone due to pregnancy may affect the degree of such hypotension. The perfusion index (PI) derived from a pulse oximeter has been used for assessing peripheral perfusion dynamics due to changes in peripheral vascular tone. The aim of this study was to examine whether baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery. Parturients undergoing elective Caesarean delivery under spinal anaesthesia with hyperbaric bupivacaine 10 mg and fentanyl 20 μg were enrolled in this prospective study. The correlation between baseline PI and the degree of hypotension during spinal anaesthesia and also the predictability of spinal anaesthesia-induced hypotension during Caesarean delivery by PI were investigated. Baseline PI correlated with the degree of decreases in systolic and mean arterial pressure (r=0.664, P<0.0001 and r=0.491, P=0.0029, respectively). The cut-off PI value of 3.5 identified parturients at risk for spinal anaesthesia-induced hypotension with a sensitivity of 81% and a specificity of 86% (P<0.001). The change of PI in parturients with baseline PI ≤ 3.5 was not significant during the observational period, while PI in parturients with baseline PI>3.5 demonstrated marked decreases after spinal injection. We demonstrated that higher baseline PI was associated with profound hypotension and that baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery.

Relation between adolescent idiopathic scoliosis and morphologic somatotypes.

PubMed

LeBlanc, R; Labelle, H; Rivard, C H; Poitras, B

1997-11-01

A prospective and controlled comparative study. To verify the difference in morphologic appearance between a group of adolescents with progressive adolescent idiopathic scoliosis and a control group of normal adolescents. In a previous retrospective study, the possibility of a relation between progressive adolescent idiopathic scoliosis and specific morphotypes was demonstrated. Fifty-two adolescent girls with progressive adolescent idiopathic scoliosis were compared with an age-matched control group of 62 unaffected girls using a classification technique based on morphologic somatotypes. Morphotypes were evaluated with standardized pre-established criteria based on Sheldon's technique. Patients with progressive adolescent idiopathic scoliosis showed significantly less mesomorphism (mean value of 0.88 +/- 0.51) than control girls (mean value of 1.72 +/- 0.52). Adolescent girls with progressive adolescent idiopathic scoliosis have a morphologic somatotype that is different from the normal adolescent population. Subjects with progressive adolescent idiopathic scoliosis are significantly less mesomorphic than control girls. This observation may be of value as a predictive factor for early identification of subjects with adolescent idiopathic scoliosis at greater risk of progression.

Perspective: Update on Idiopathic Intracranial Hypertension

PubMed Central

Bruce, Beau B.; Biousse, Valérie; Newman, Nancy J.

2011-01-01

Purpose Provide an update on various features of idiopathic intracranial hypertension. Design Perspective. Methods Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience. Results Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting. Conclusions Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension. PMID:21696699

Subclinical decelerations during developing hypotension in preterm fetal sheep after acute on chronic lipopolysaccharide exposure

PubMed Central

Lear, Christopher A.; Davidson, Joanne O.; Galinsky, Robert; Yuill, Caroline A.; Wassink, Guido; Booth, Lindsea C.; Drury, Paul P.; Bennet, Laura; Gunn, Alistair J.

2015-01-01

Subclinical (shallow) heart rate decelerations occur during neonatal sepsis, but there is limited information on their relationship with hypotension or whether they occur before birth. We examined whether subclinical decelerations, a fall in fetal heart rate (FHR) that remained above 100 bpm, were associated with hypotension in preterm fetal sheep exposed to lipopolysaccharide (LPS). Chronically-instrumented fetal sheep at 0.7 gestation received continuous low-dose LPS infusions (n = 15, 100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h) or saline (n = 8). Boluses of 1 μg LPS or saline were given at 48 and 72 h. FHR variability (FHRV) was calculated, and sample asymmetry was used to assess the severity and frequency of decelerations. Low-dose LPS infusion did not affect FHR. After the first LPS bolus, 7 fetuses remained normotensive, while 8 developed hypotension (a fall in mean arterial blood pressure of ≥5 mmHg). Developing hypotension was associated with subclinical decelerations, with a corresponding increase in sample asymmetry and FHRV (p < 0.05). The second LPS bolus was associated with similar but attenuated changes in FHR and blood pressure (p < 0.05). In conclusion, subclinical decelerations are not consistently seen during prenatal exposure to LPS, but may be a useful marker of developing inflammation-related hypotension before birth. PMID:26537688

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

A unifying hypothesis for a patient with superficial siderosis, low-pressure headache, intraspinal cyst, back pain, and prominent vascularity.

PubMed

Kumar, Neeraj; Miller, Gary M; Piepgras, David G; Mokri, Bahram

2010-07-01

A source of bleeding is often not evident during the evaluation of patients with superficial siderosis of the CNS despite extensive imaging. An intraspinal fluid-filled collection of variable dimensions is frequently observed on spine MR imaging in patients with idiopathic superficial siderosis. A similar finding has also been reported in patients with idiopathic intracranial hypotension. The authors report on a patient with superficial siderosis and a longitudinally extensive intraspinal fluid-filled collection secondary to a dural tear. The patient had a history of low-pressure headaches. His spine MR imaging and spine CT suggested the possibility of an underlying vascular malformation, but none was found on angiography. Repair of the dural tear resulted in resolution of the intraspinal fluid collection and CSF abnormalities. The significance of the association between superficial siderosis and idiopathic intracranial hypotension, and potential therapeutic and pathophysiological implications, are the subject of this report.

Report on 50 cases of severe acute hypotension at donor plasmaphereses: treatment and course.

PubMed

Evers, Josef; Schreiber, George B; Taborski, Uwe

2017-05-29

This paper reports our experience in 50 cases with severe hypotensive reactions at plasma donations (synonymous with donor plasmaphereses). Plasma donors who developed a severe acute hypotensive reaction at donor plasmapheresis, and were treated by placing the donor in the Trendelenburg position and rapid infusion of 1,000 mL saline were investigated. Plasmaphereses were performed with the Haemonetics® plasma collecting system 2 (PCS2). The results were analyzed using Excel. We observed 50 severe hypotensive reactions in plasma donors. The average systolic and diastolic blood pressures (SBP, DBP) were 128/75 mmHg - and heart rates were 78 beats/min (B/M) before plasmaphereses, 83/56 mmHg - 60 B/M at the event, and after treatment 119/71 mmHg - 69 B/M at the time of discharge. The volume of collected plasma was 602 ± 240 mL including anticoagulant (AC). The time until the event was 45 ± 20 minutes. With treatment 49 ± 18 minutes after the event all plasma donors had normal blood pressures and heart rates and could safely leave the center. Treatment by placing the donor in the Trendelenburg position and rapid infusion of 1,000 mL saline appears to be an effective procedure for resolving severe acute hypotension associated with donor plasmaphereses.

L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.

PubMed

Goldstein, David S

2006-01-01

L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

Etiology of Syncope and Unexplained Falls in Elderly Adults with Dementia: Syncope and Dementia (SYD) Study.

PubMed

Ungar, Andrea; Mussi, Chiara; Ceccofiglio, Alice; Bellelli, Giuseppe; Nicosia, Franco; Bo, Mario; Riccio, Daniela; Martone, Anna Maria; Guadagno, Livia; Noro, Gabriele; Ghidoni, Giulia; Rafanelli, Martina; Marchionni, Niccolò; Abete, Pasquale

2016-08-01

To investigate the etiology of transient loss of consciousness (T-LOC) suspected to be syncope and unexplained falls in elderly adults with dementia. Prospective, observational, multicenter study. Acute care wards, syncope units or centers for the diagnosis of dementia. Individuals aged 65 and older with a diagnosis of dementia and one or more episodes of T-LOC of a suspected syncopal nature or unexplained falls during the previous 3 months were enrolled. The causes of T-LOC suspected to be syncope and unexplained falls were evaluated using a simplified protocol based on European Society of Cardiology guidelines. Of 357 individuals enrolled, 181 (50.7%) had been referred for T-LOC suspected to be syncope, 166 (46.5%) for unexplained falls, and 10 (2.8%) for both. An initially suspected diagnosis of syncope was confirmed in 158 (87.3%), and syncope was identified as the cause of the event in 75 (45.2%) of those referred for unexplained falls. Orthostatic hypotension was the cause of the event in 117 of 242 (48.3%) participants with a final diagnosis of syncope. The simplified syncope diagnostic protocol can be used in elderly people with dementia referred for suspected syncope or unexplained falls. Unexplained falls may mask a diagnosis of syncope or pseudosyncope in almost 50% of cases. Given the high prevalence of orthostatic syncope in participants (~50%), a systematic reappraisal of drugs potentially responsible for orthostatic hypotension is warranted. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Blood pressure and heart rate during orthostatic stress and walking with continuous postoperative thoracic epidural bupivacaine/morphine.

PubMed

Møiniche, S; Hjortsø, N C; Blemmer, T; Dahl, J B; Kehlet, H

1993-01-01

Thirty-one patients scheduled for elective cholecystectomy performed through a mini-laparotomy, were randomized to received either combined thoracic epidural anaesthesia/light general anaesthesia and postoperative balanced analgesia with continuous epidural bupivacaine 10 mg.h-1 and morphine 0.2 mg.h-1 for 38 h after surgery plus systemic ibuprofen 600 mg x 8 h-1 (N = 15) or general anaesthesia and postoperative analgesia with systemic morphine and ibuprofen 600 mg x 8 h-1 (N = 16). During postoperative epidural infusion sensory blockade to pinprick was Th4 to L1, and analgesia at rest and during mobilisation was superior compared to systemic morphine and NSAID. There were no significant differences between groups in haemodynamic responses (BP and heart rate) during rest, orthostatic stress and after walking assessed before, 24 and 48 h after operation except for a clinically unimportant lower heart rate (approximately 10 bpm) 48 h after surgery at rest and during orthostatic stress in the epidural group. There was no significant difference between groups in number of patients with a reduction > 20 mmHg (2.7 kPa) in systolic blood pressure during orthostatic stress (two in each group at 24 h) or in number of episodes of dizziness, nausea or vomiting during rest or mobilisation. These results do not support the common belief that low-dose thoracic epidural bupivacaine/morphine may prevent ambulation due to sympathetic blockade or to impaired cardiovascular adaptation to the upright position.

The Natural History of Idiopathic Scoliosis During Growth: A Meta-Analysis.

PubMed

Di Felice, Francesca; Zaina, Fabio; Donzelli, Sabrina; Negrini, Stefano

2018-05-01

The aim of the study was to provide a meta-analysis of current literature concerning the natural history of idiopathic scoliosis during growth. A comprehensive search of Medline, Embase, And Scopus databases was conducted up to November 2016. Eligible works were prospective or retrospective studies that enrolled patients with infantile idiopathic scoliosis, juvenile idiopathic scoliosis, or adolescent idiopathic scoliosis, followed up without any treatment from the time of detection. A meta-analysis for proportion was performed. The following studies were grouped per diagnosis: infantile idiopathic scoliosis, juvenile idiopathic scoliosis, and adolescent idiopathic scoliosis. Of the 1797 citations screened, we assessed 61 full-text articles and included 13 of these (2301 participants). Three studies included infantile idiopathic scoliosis patients (347 participants), five studies included a mixed population of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis (1330 participants), and five studies included adolescent idiopathic scoliosis patients only (624 participants). The random pooled estimated progression rate was 49% (95% confidence interval = 1%-97%) for infantile idiopathic scoliosis, 49% in a mixed group of patients affected by juvenile idiopathic scoliosis or adolescent idiopathic scoliosis (95% confidence interval = 19%-79%), and 42% in adolescent idiopathic scoliosis (95% confidence interval = 11%-73%). During growth, idiopathic scoliosis tends to progress in a high percentage of cases. The progression rate varies according to the age at diagnosis, with infantile scoliosis being the most unpredictable. There are many confounders, such as age, Risser sign and baseline Cobb angles that were not consistent among studies, making the data very heterogeneous.

Idiopathic sudden sensorineural hearing loss and ménière syndrome: The role of cerebral venous drainage.

PubMed

Ciccone, M M; Scicchitano, P; Gesualdo, M; Cortese, F; Zito, A; Manca, F; Boninfante, B; Recchia, P; Leogrande, D; Viola, D; Damiani, M; Gambacorta, V; Piccolo, A; De Ceglie, V; Quaranta, N

2018-02-01

To evaluate the influence of cerebral venous drainage on the pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) and Ménière syndrome (MD). Observational, prospective, cohort study. ENT and Cardiology Departments (University of Bari, Policlinico Hospital, Bari, Italy). We enrolled 59 consecutive patients (32 males, mean age 53.05 + 15.37 years): 40 ISSHL and 19 MD. All patients underwent physical examination, biochemical evaluation (glycemic and lipid profile, viral serology, C reactive protein, etc), audiometric (tonal, vocal, vestibular evoked myogenic potentials and auditory brainstem response test) and impedentiometric examination. The pure tone average (PTA) was calculated for the following frequencies: 250, 500, 1000, 2000, 3000, 4000, 8000. An echo-color Doppler evaluation of the venous cerebral veins, internal jugular (IJV) and vertebral veins (VV) at supine and 90° position was performed. No morphological alterations were found both in patients and controls. There were no signs of stenosis, blocked flow, membranes, etc. We found lower minimum, mean and maximum velocities in distal IJVs (P = .019; P = .013; P = .022; respectively) and left VVs (P = .027; P = .008; P = .001; respectively) in supine (0°) position in both MD and ISSHL patients as compared to controls. The same was for orthostatic position (90°). We found negative correlations between the velocities in extracranial veins and PTA values: therefore, the worst the audiometric performance of the subjects, the lower the velocities in the venous cerebral drainage. Idiopathic sudden sensorineural hearing loss and Ménière syndrome patients showed altered venous flow in IJVs and VVs as compared to controls, independently from posture. This different behavior of venous tone control can influence the ear performance and may have a role in the pathogenesis of both diseases. © 2017 John Wiley & Sons Ltd.

The organizational structure of an intensive care unit influences treatment of hypotension among critically ill patients: A retrospective cohort study

PubMed Central

Boone, M. Dustin; Massa, Jennifer; Mueller, Ariel; Jinadasa, Sayuri P; Lee, Joon; Kothari, Rishi; Scott, Daniel J.; Callahan, Julie; Celi, Leo Anthony; Hacker, Michele R.

2016-01-01

Purpose Prior studies report that weekend admission to an intensive care unit is associated with increased mortality, potentially attributed to the organizational structure of the unit. This study aims to determine whether treatment of hypotension, a risk factor for mortality, differs according to level of staffing. Methods Using the Multiparameter Intelligent Monitoring in Intensive Care database, we conducted a retrospective study of patients admitted to an intensive care unit at Beth Israel Deaconess Medical Center who experienced one or more episodes of hypotension. Episode(s) were categorized according to the staffing level, defined as high during weekday daytime (7am–7pm) and low during weekends or nighttime (7pm–7am). Results Patients with a hypotensive event on a weekend were less likely to be treated compared to those that occurred during the weekday daytime (p=0.02). No association between weekday daytime versus weekday nighttime staffing levels and treatment of hypotension was found (RR 1.02; 95% CI 0.98–1.07). Conclusion Patients with a hypotensive event on a weekend were less likely to be treated than patients with an event during high-staffing periods. No association between weekday nighttime staffing and hypotension treatment was observed. We conclude that treatment of a hypotensive episode relies on more than solely staffing levels. PMID:26975737

Entropy-based complexity of the cardiovascular control in Parkinson disease: comparison between binning and k-nearest-neighbor approaches.

PubMed

Porta, Alberto; Bari, Vlasta; Bassani, Tito; Marchi, Andrea; Tassin, Stefano; Canesi, Margherita; Barbic, Franca; Furlan, Raffaello

2013-01-01

Entropy-based approaches are frequently used to quantify complexity of short-term cardiovascular control from spontaneous beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP). Among these tools the ones optimizing a critical parameter such as the pattern length are receiving more and more attention. This study compares two entropy-based techniques for the quantification of complexity making use of completely different strategies to optimize the pattern length. Comparison was carried out over HP and SAP variability series recorded from 12 Parkinson's disease (PD) patients without orthostatic hypotension or symptoms of orthostatic intolerance and 12 age-matched healthy control (HC) subjects. Regardless of the method, complexity of cardiovascular control increased in PD group, thus suggesting the early impairment of cardiovascular function.

[Gastric dynamics analysis of TEAS combined SNP induced general anesthesia when controlled hypotension dropped to 60% of the MAP baseline].

PubMed

Zhang, Le-Le; Fang, Jian-Qiao; Shao, Xiao; Lian, Lin-Li; Yu, Xiao-Jing; Dong, Zhen-Hua; Mo, Ya-Di

2015-01-01

To observe the effect of gastric dynamics by transcutaneous electrical acupoint stimulation (TEAS) combined general anesthesia when controlled hypotension dropped to 60% of the mean arterial prenssure (MAP) baseline, and to provide experimental evidence for organ protection in clinical controlled hypotension. Eighteen male beagles were randomly divided into three groups, the general anesthesia group (blank), the general anesthesia induced controlled hypotension group (control), and the general anesthesia combined TEAS induced controlled hypotension group (experiment), 6 in each group. Controlled hypotension was performed in the latter two groups with isoflurane inhalation and intravenous injection of sodium nitroprusside (SNP). The mean arterial pressure (MAP) was lowered to 60% of the MAP baseline and kept for 60 min. Controlled hypotension was not performed in Beagles of the control group. For Beagles in the experiment group, TEAS [2/100 Hz, (4 ± 1) mA] was applied to bilateral Hegu (LI4), Quchi (LI11), Zusanli (ST36), and Sanyinjiao (SP6) from stable physiological conditions to the end of maintaining stages. Changes of EGG frequencies and EGG amplitudes were monitored. Serum levels of gastrin (GAS) and motilin (MTL) were also detected at corresponding time points during and after experiment. As for the pressure control effect of TEAS combined general anesthesia in the controlled hypotension, during the process of controlled hypotension (T1-T4), MAP levels of two controlled pressure groups remained relatively stable, and were kept at 60% of the MAP baseline. When the blood pressure dropped to the target low MAP and maintained at 60 min (T1-T4), EGG amplitudes of Beagles in all the three groups showed decreasing tendency. But it was more obviously lower than its basic level in the control group (P <0.05), while it was not obviously decreased in the experiment group (P < 0.05). EGG frequencies of Beagles in all the three groups showed no obvious change during this

Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

NASA Technical Reports Server (NTRS)

Zhang, R.; Behbehani, K.; Crandall, C. G.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

2001-01-01

To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

[Intra-anesthetic arterial hypotension in elderly patients during emergency surgery: what are the risk factors?

PubMed

Boubacar Ba, El Hadji; Leye, Papa Alassane; Traoré, Mamadou Mour; Ndiaye, Pape Ibrahima; Gaye, Ibrahima; Bah, Mamadou Diawo; Fall, Mamadou Lamine; Diouf, Elisabeth

2017-01-01

Emergency anesthesia in elderly patients aged 65 years and older is complex. The occurrence of intraoperative incidents and arterial hypotension is conditioned by patients' initial health status and by the quality of intraoperative management. This study aimed to determine the incidence of intra-anesthetic arterial hypotension in elderly patients during emergency surgery and to assess the involvement of certain factors in its occurrence: age, sex, patient's history, ASA class, anesthetic technique. We conducted a retrospective descriptive and analytical study in the Emergency Surgery Department at the Aristide Le Dantec University Hospital from 1 March 2014 to 28 February 2015. We collected data from 210 patients out of 224 elderly patients aged 65 years and older undergoing emergency anesthesias (10.93%). Data of 101 men and 109 women were included in the analysis, of whom 64.3% had at least one defect. Patients' preoperative status was assessed using American Society of Anesthesiology (ASA) classification: 71% of patients were ASA class 1 and 2 and 29% were ASA class 3 and 4. Locoregional anesthesia was the most practiced anesthetic technique (56.7%). 28 patients (13.33%) had intra-anesthetic arterial hypotension, of whom 16 under general anesthesia and 12 under locoregional anesthesia. It was more frequent in patients with high ASA class and a little less frequent in patients with PAH and underlying heart disease. Arterial hypotension in elderly patients during emergency surgery exposes the subject to the risk of not negligible intraoperative hypotension, especially in patients with high ASA class. Prevention is based on adequate preoperative assessment and anesthetic management.

Pulse Rate and Transit Time Analysis to Predict Hypotension Events After Spinal Anesthesia During Programmed Cesarean Labor.

PubMed

Bolea, Juan; Lázaro, Jesús; Gil, Eduardo; Rovira, Eva; Remartínez, José M; Laguna, Pablo; Pueyo, Esther; Navarro, Augusto; Bailón, Raquel

2017-09-01

Prophylactic treatment has been proved to reduce hypotension incidence after spinal anesthesia during cesarean labor. However, the use of pharmacological prophylaxis could carry out undesirable side-effects on mother and fetus. Thus, the prediction of hypotension becomes an important challenge. Hypotension events are hypothesized to be related to a malfunctioning of autonomic nervous system (ANS) regulation of blood pressure. In this work, ANS responses to positional changes of 51 pregnant women programmed for a cesarean labor were explored for hypotension prediction. Lateral and supine decubitus, and sitting position were considered while electrocardiographic and pulse photoplethysmographic signals were recorded. Features based on heart rate variability, pulse rate variability (PRV) and pulse transit time (PTT) analysis were used in a logistic regression classifier. The results showed that PRV irregularity changes, assessed by approximate entropy, from supine to lateral decubitus, and standard deviation of PTT in supine decubitus were found as the combination of features that achieved the best classification results sensitivity of 76%, specificity of 70% and accuracy of 72%, being normotensive the positive class. Peripheral regulation and blood pressure changes, measured by PRV and PTT analysis, could help to predict hypotension events reducing prophylactic side-effects in the low-risk population.

Postural orthostatic tachycardia syndrome: Dental treatment considerations.

PubMed

Brooks, John K; Francis, Laurie A P

2006-04-01

Postural orthostatic tachycardia syndrome (POTS) is a chronic, relatively common autonomic disorder typically affecting younger females. It is distinguished by a dramatic increase in heart rate on the assumption of an upright posture from the supine position. The authors provide an overview of the demographics, clinical assessment, diagnostic features, differential diagnoses, pathogeneses and medical treatment of patients with POTS, with an emphasis on the clinical treatment of the dental patient affected by the syndrome. Patients frequently exhibit symptoms of lightheadedness, fatigue, palpitations and syncope. Patients with POTS may have Ehlers-Danlos syndrome, mitral valve prolapse, chronic fatigue syndrome or, rarely, the Brugada syndrome. Despite widespread dissemination of information regarding POTS in the medical literature, scant information on it has appeared in dental publications. Dentists need to be familiar with the clinical features of POTS and be prepared to treat patients at risk of developing syncope.

Idiopathic Hypersomnia: A Study of 77 Cases

PubMed Central

Anderson, Kirstie N.; Pilsworth, Samantha; Sharples, Linda D.; Smith, Ian E.; Shneerson, John M.

2007-01-01

Study Objectives: To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. Setting: The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. Patients and Design: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Measurements and Results: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Conclusions: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve. Citation: Anderson KN; Pilsworth S; Sharples LD; Smith IE; Shneerson JM. Idiopathic

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma.

PubMed

Dai, Jin; Chen, Shen-Jie; Yang, Bing-Sheng; Lü, Shu-Min; Zhu, Min; Xu, Yi-Fei; Chen, Jie; Cai, Hong-Wen; Mao, Wei

2017-05-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed.

Alanine increases blood pressure during hypotension