Role of Sympathetic Activity and Splanchnic Capacitance in Hypertension
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|ClinicalTrials.gov Identifier: NCT02425566|
Recruitment Status : Suspended (Recruitment is temporarily suspended due to COVID-19 outbreak)
First Posted : April 24, 2015
Last Update Posted : April 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hypertension||Drug: Trimethaphan Drug: Nitroglycerin||Phase 1|
The splanchnic circulation contains a highly compliant venous bed which normally stores ~25% of the blood volume, and receives up to 25% of the resting cardiac output. It is highly innervated by the sympathetic nervous system, and this neural regulation results in large volume shifts that modulate blood pressure (BP). The splanchnic circulation may play a role in hypertension as suggested by studies showing that surgical splanchnic denervation effectively lowered BP in hypertensive subjects without affecting renal function. Recently, studies in animal models have shown that splanchnic sympathetic activation, particularly to capacitance vessels, was critical to the development of hypertension. The clinical translation of these findings to human hypertension has lagged behind because of limitations in previously available experimental approaches. The investigators propose to use splanchnic radionuclide plethysmography and sympathetic withdrawal with the ganglionic blocker trimethaphan to overcome these limitations.
Several studies have shown that sympathetic activity contributes to hypertension. Accordingly, our previous studies showed that sympathetic withdrawal with the ganglionic blocker trimethaphan resulted in normalization of BP in hypertensive subjects. Interestingly, this was caused mainly by a fall in stroke volume, rather than a decrease in arterial vascular resistance suggesting that decreased venous return may play a major role, and that a sympathetically mediated contraction of splanchnic capacitance contributes to the maintenance of hypertension.
The investigators hypothesize that the decrease in BP induced by autonomic blockade with trimethaphan results from an increase in splanchnic capacitance leading to a reduction in venous return. To test this hypothesis, the investigators will compare the effect of sympathetic withdrawal on splanchnic capacitance between hypertensive and normotensive subjects. Splanchnic venous capacitance will be measured by radionuclide plethysmography. Abdominal blood volumes will be measured using labeled red cells with technetium-99 while applying different levels of continuous positive airway pressure.
In addition, the investigators will assess whether changes in splanchnic capacitance measured by bioimpedance are similar to those measured by radionuclide imaging. For this purpose, the investigators will compare the effects of nitroglycerin on splanchnic capacitance measured by the two techniques.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Role of Sympathetic Activity and Splanchnic Capacitance in Hypertension|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||August 2021|
Experimental: Study day with trimethaphan
After baseline measurements, autonomic blockade will be induced by continuous intravenous infusion of trimethaphan starting at 0.5-1.0 mg/min and increasing by 1.0 mg/min every 2 to 6 minutes up to an infusion rate of 5 mg/min.
Trimethaphan is a Nn-nicotinic receptor antagonist that blocks sympathetic and parasympathetic transmission at the level of the autonomic ganglia. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 5.0 mg/min.
Other Name: Trimethaphan Camsylate
Experimental: Radionuclide Study day with nitroglycerin
Sublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements. Outcome measurements will be repeated within 10 min after the nitroglycerin has dissolved
Sublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements.
Other Name: Nitroglycerin sublingual, nitrostat
- Splanchnic venous capacitance [ Time Frame: after 10 minutes of autonomic blockade ]The primary outcome will be the splanchnic capacitance, defined as the pressure-venous curve (P-V curve), during trimethaphan infusion adjusted for its baseline values. For analysis, the Y-intercept (volume) and the slope of the P-V relationship during autonomic blockade adjusted by their corresponding baseline values will be compared between groups.
- Systolic Blood Pressure [ Time Frame: after 10 minutes of autonomic blockade ]Changes from baseline in blood pressure.
- Stroke volume [ Time Frame: after 10 minutes of autonomic blockade ]Changes from baseline in stroke volume.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02425566
|United States, Tennessee|
|Autonomic Dysfunction Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Italo Biaggioni, MD||Vanderbilt University|