Endothelial Hyperpolarization in Humans

This study has been terminated.
(Limited clinical staff)
Sponsor:
Information provided by (Responsible Party):
Arshed A. Quyyumi, Emory University
ClinicalTrials.gov Identifier:
NCT00166166
First received: September 13, 2005
Last updated: May 12, 2015
Last verified: May 2015

September 13, 2005
May 12, 2015
July 2002
January 2013   (final data collection date for primary outcome measure)
  • Percent Change in Forearm Blood Flow (FBF) After Tetraethylammonium (TEA) Administration [ Time Frame: Baseline, 5 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after TEA administration.
  • Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA) [ Time Frame: Baseline, 5 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of L-NG-monomethyl Arginine (L-NMMA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF from baseline and after L-NMMA administration.
Bradykinin mediated forearm blood flow.
Complete list of historical versions of study NCT00166166 on ClinicalTrials.gov Archive Site
  • Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA) [ Time Frame: 5 minutes, 10 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF from after L-NMMA administration and after TEA administration.
  • Percent Change in Forearm Blood Flow (FBF) After Fluconazole Administration [ Time Frame: Baseline, 5 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of fluconazole. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after fluconazole administration.
  • Percent Change in Forearm Blood Flow (FBF) After L-NG-monomethyl Arginine (L-NMMA) and Fluconazole Administration [ Time Frame: 5 minutes, 10 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after L-NMMA administration and administration of fluconazole. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF after L-NMMA administration and then fluconazole administration.
  • Percent Change in Forearm Blood Flow (FBF) After Fluconazole and Tetraethylammonium (TEA) Administration [ Time Frame: 5 minutes, 10 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of fluconazole and Tetraethylammonium (TEA) administration. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from FBF after fluconazole administration and after Tetraethylammonium (TEA) administration.
  • Forearm Blood Flow (FBF) After Sodium Nitroprusside Administration [ Time Frame: 5 minutes ] [ Designated as safety issue: No ]
    Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of sodium nitroprusside. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed.
  • Change in Tissue Plasminogen Activator (t-PA) Release [ Time Frame: Baseline, 30 minutes ] [ Designated as safety issue: No ]
    Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA at baseline and t-PA after bradykinin 400 ng/min
  • Change in Tissue Plasminogen Activator (t-PA) Release After Tetraethylammonium (TEA) and Bradykinin Administration [ Time Frame: 30 minutes, 60 minutes ] [ Designated as safety issue: No ]
    Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after Tetraethylammonium (TEA) and t-PA after bradykinin 400 ng/min
  • Change in Tissue Plasminogen Activator (t-PA) Release After Fluconazole and Bradykinin Administration [ Time Frame: 30 minutes, 60 minutes ] [ Designated as safety issue: No ]
    Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after fluconazole and t-PA after bradykinin 400 ng/min
  • Change in Tissue Plasminogen Activator (t-PA) Release After Fluconazole, Tetraethylammonium (TEA), and Bradykinin Administration [ Time Frame: 60 minutes, 90 minutes ] [ Designated as safety issue: No ]
    Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after fluconazole and tetraethylammonium (TEA) and t-PA after bradykinin 400 ng/min
Not Provided
Not Provided
Not Provided
 
Endothelial Hyperpolarization in Humans
Physiology and Pathologic Role of Endothelium-Derived Hyperpolarizing Factor in Humans

The purpose of this study is to elucidate the role Endothelium-Derived Hyperpolarizing Factor (EDHF) plays in dilating blood vessels and whether it differs between healthy people and those with high cholesterol. A second purpose of the study is to determine the identity of EDHF.

The vascular endothelium synthesizes at least four potent vasodilator substances: nitric oxide (NO), prostacyclin, carbon monoxide and endothelium-derived hyperpolarizing factor (EDHF) that contribute to vasodilator tone, and to inhibition of platelet activation and inflammation. EDHF release is stimulated by receptor-dependent agonists such as acetylcholine and bradykinin (BK), and leads to hyperpolarization of the underlying smooth muscle cells presumably by opening Ca2+-activated K+ channels. Indirect pharmacological evidence suggests that EDHF is a cytochrome P450-derived arachidonic acid metabolite, presumably an epoxide. Although the pivotal role of NO to conduit vessel dilation in response to acute increases in shear stress is well known, its' contribution to dilation with sustained increases in flow are minimal, and may be due to EDHF release.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Hyperlipidemia
  • Drug: Tetraethylammonium (TEA)
    5 minute intra-arterial infusion of Tetraethylammonium at 1 mg/min
  • Drug: L-NG-monomethyl Arginine (L-NMMA)
    5 minute intra-arterial infusion of L-NMMA 8 μmol/min
    Other Name: Methylarginine
  • Drug: Bradykinin
    Intra-arterial infusion of bradykinin at 100, 200, and 400 ng/min. Each dose will be given for 5 minutes.
  • Drug: Sodium nitroprusside
    Intra-arterial infusion of sodium nitroprusside at 1.6 and 3.2 mg/min. Each dose will be given for 5 minutes.
    Other Name: Nitropress
  • Drug: Acetylcholine
    Intra-arterial infusion of acetylcholine at 7.5, 15 and 30 μg/min. Each dose will be given for 5 minutes.
  • Drug: Saline
    5 minute intra-arterial infusion of 0.9% saline at 2.5ml/min
  • Drug: Fluconazole
    5 minute intra-arterial infusion of fluconazole at 0.4 mg/L/min
    Other Name: Diflucan
  • Experimental: Healthy Controls
    Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine
    Interventions:
    • Drug: Tetraethylammonium (TEA)
    • Drug: L-NG-monomethyl Arginine (L-NMMA)
    • Drug: Bradykinin
    • Drug: Sodium nitroprusside
    • Drug: Acetylcholine
    • Drug: Saline
    • Drug: Fluconazole
  • Experimental: Risk Factors
    Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine
    Interventions:
    • Drug: Tetraethylammonium (TEA)
    • Drug: L-NG-monomethyl Arginine (L-NMMA)
    • Drug: Bradykinin
    • Drug: Sodium nitroprusside
    • Drug: Acetylcholine
    • Drug: Saline
    • Drug: Fluconazole

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
174
January 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Hyperlipidemic (LDL > 140)
  • Healthy Volunteer

Exclusion Criteria:

  • Pregnancy
  • Diabetes mellitus
  • Cardiovascular Disease
  • Hypertension
  • Use of any regular medications
  • Renal insufficiency
  • Smoking (current or within the past 5 years)
  • Bleeding disorder
Both
21 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00166166
IRB00021886, 1 RO1 HL079115-01, 0605-2002
No
Arshed A. Quyyumi, Emory University
Emory University
Not Provided
Principal Investigator: Arshed A Quyyumi, MD Emory University School of Medicine, Division of Cardiology
Emory University
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP