Characterization of Brachial Arterial t-PA Release, Endothelial Function, Obesity and Inflammation

Study Overview
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Brief Summary
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T-PA release is impaired in obese subjects. In order to have a better mechanistic understanding of t-PA release, we will compare t-PA release to Flow Mediated Vasodilation, Radial Artery Tonometry, and other markers of endothelial function and oxidative stress.

Official Title
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Characterization of Brachial Arterial t-PA Release, Vasodilator Function, and Vascular Compliance and Correlation With Fibrinolytic Balance, Oxidative Stress, and Inflammation Measures (SCCOR Project 1 Aim 3B)

Conditions
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Obesity

Intervention / Treatment
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* Drug: Bradykinin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adults 18 years and greater Healthy Exclusion criteria: PVC < 30 Hypertensive subjects on ACE inhibitors Pregnant or nursing mothers Diabetic with HbA1C > 7.5 or stigmata of end organ damage (neuropathy, retinopathy, nephropathy, cardiomyopathy) Cholesterol > 30 mg/dL above NCEP accepted level based on cardiac risk. Triglycerides > 200 Previously diagnosed obstructive coronary artery disease, myocardial infarction or left ventricular dysfunction (with or without a history of congestive heart failure) Renal insufficiency (Creatinine ≥ 1.5 mg/dl) History of cerebrovascular disease Any chronic inflammatory disease (rheumatologic, inflammatory bowel disease, etc) Uncontrolled Stage 2 Hypertension (160/100 mmHg), or end organ damage due to hypertension (left ventricular hypertrophy, atrial fibrillation, hematuria, renal insufficiency, prior cerebrovascular disease). Angiotensin converting enzyme inhibitor use Coagulopathy (INR ≥ 1.5, PTT ≥ 1.5 x control) Other chronic medical illnesses at the discretion of the investigators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bradykinin<br>Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. | Drug: Bradykinin<br>* Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak t-PA Release | tPA Release | Single Study day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak FMD |  | Single Study Day | 
| Radial Artery Elasticity |  | Single Study Visit | 
| Lipid Levels, PAI-1 Levels, CRP Levels, F2 Isoprostanes and Other Biomarkers of Inflammation and Obesity. |  | Single Study Day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Endothelial Function, Fibrinolytic Balance, Baseline