Track topics on Twitter Track topics that are important to you
The purpose of this study is to test the hypothesis that endothelin plays a role in the pathogenesis of supine hypertension in pure autonomic failure by increasing vascular resistance. To gauge its contribution to blood pressure regulation, pure autonomic failure and multiple system atrophy patients with supine hypertension will undergo a medication testing with the endothelin blocker, BQ123. We will compare the hemodynamic effects between PAF and MSA patients. Our primary endpoint will be the decrease in blood pressure during the administration of this compound.
The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure are not completely understood.In MSA patients, supine hypertension may be explained by residual sympathetic tone, possibly acting on hypersensitive adrenoreceptors and unstrained by the lack of baroreflex modulation. In contrast, the pathogenesis of hypertension in PAF remains unknown. Hypertension in these patients is not related to intravascular volume, residual sympathetic tone, or renin mechanisms. Increased vascular resistance is the underlying hemodynamic mechanism. The driving force of this increased vascular tone, however, is not known.
We hypothesize that endothelin (ET)-l contributes to the increased vascular resistance in pure autonomic failure patients with supine hypertension. To gauge its contribution to blood pressure regulation, we will induce endothelin blockade with acute systemic administration of BQ123 in an ascending dose regimen (25, 50, 100 and 300 nmol/min) and we will compare the hemodynamic effects between PAF and MSA patients.
Subjects will be studied on 3 different days, one with saline (placebo) and two with BQ123: a 'low dose' day (25 and 50 nmol/min infusions separated by 75 min) and a 'high dose' day (100 and 300 nmol/min infusions separated by 75 min). The order of the placebo day will be randomized in a single-blinded manner so that each subject receives it on a different visit. The order of the BQ123 study days will be always the same, starting with the low dose. If SBP drops by >40 mm Hg or SBP < 130 mm Hg during the monitoring period after the first or second infusion, the following dose(s) of BQ123 will not be given and patients will receive normal saline until the study ends.
Ganglionic Blockade with Trimethaphan (optional study day):
The purpose of this study day is to determine the level of residual sympathetic tone that contributes to supine hypertension in each autonomic failure patient by inducing transient withdrawal of the autonomic nervous system. This approach would allow us to identify patients in whom supine hypertension is not driven by sympathetic tone and thus, better characterize the role of endothelin in the hypertension of these patients.
Allocation: Randomized, Control: Placebo Control, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject)
BQ123, BQ123, Bq123, BQ123, Saline
Published on BioPortfolio: 2014-08-27T03:13:52-0400
Background: Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endotheli...
Osmotherapy consists in the therapeutic use of osmotically active substances with the aim of reducing the volume and therefore the intracranial pressure. It therefore represents an essenti...
The purpose of this prospective randomized double-blind study is to determine if the novel technique of ultrasound guided peri-arterial injection of local anesthetic around the femoral art...
The purpose of this study is to determine whether hypertonic saline is as much effective as mannitol to treat intracranial hypertension after traumatic brain injury and has at least the sa...
A comparison of albuterol treatments using hypertonic saline (3%) versus standard saline (0.9%) in patients with admitted patients COPD in regard to Modified Borg Dyspnea scale scores afte...
Hypertension is an independent risk factor for diabetic retinopathy, yet anti-hypertensive medications such as blockade of angiotensin II do not completely protect against vision-threatening vascular ...
Cerebral vasospasm may lead to delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH). Endothelin (ET-1) is an important factor participating in cerebral vasospasm underlying S...
Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of...
Although oxygen therapy rapidly improves arterial oxygen saturation in idiopathic pulmonary arterial hypertension, the effects of chronic administration of oxygen are unknown. The purpose of the prese...
To quantitate the effect of intravenous hypertonic saline on elevated intraocular pressure (IOP) among three groups of glaucoma patients or suspects.
A genus of HALOBACTERIACEAE distinguished from other genera in the family by the presence of specific derivatives of TGD-2 polar lipids. Haloarcula are found in neutral saline environments such as salt lakes, marine salterns, and saline soils.
A family of gram-negative, moderately halophilic bacteria in the order Oceanospirillales. Members of the family have been isolated from temperate and Antarctic saline lakes, solar salt facilities, saline soils, and marine environments.
A condition in pregnant women with elevated systolic (>140 mm Hg) and diastolic (>90 mm Hg) blood pressure on at least two occasions 6 h apart. HYPERTENSION complicates 8-10% of all pregnancies, generally after 20 weeks of gestation. Gestational hypertension can be divided into several broad categories according to the complexity and associated symptoms, such as EDEMA; PROTEINURIA; SEIZURES; abnormalities in BLOOD COAGULATION and liver functions.
Hypertension due to RENAL ARTERY OBSTRUCTION or compression.
Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including AGT, GNB3, and ECE1. OMIM: 145500
Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...