Brachial Artery t-PA Release in Heart Transplant Recipients

Study Overview
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Brief Summary
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Bradykinin stimulates t-PA release from intact vessels, but not from endothelial cells in culture. It has been proposed that the nerves of blood vessels are the source of bradykinin stimulated t-PA release. In order tho test this hypothesis, we intend to infuse bradykinin into the brachial (arm) artery and the coronary arteries of heart transplant recipients and control subjects. This is because heart transplant recipients do not have nerves to their coronary arteries. This protocol studies the effects of bradykinin on t-PA release in the forearm of transplant recipients. The brachial artery has intact nerves. Separate protocols address coronary artery infusions in healthy subjects and transplant recipients and forearm infusions in healthy subjects.

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 in Heart Transplant Recipients (SCCOR Project 1, Aim 3C)

Conditions
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Heart Transplantation

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 who have undergone heart transplantation 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 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 ≥ 150% of control) Peripheral Vascular Disease 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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bradykinin<br>Patients receive 0, 10, 20, and 40 ng/min/100cc forearm volume of intrabrachial bradykinin, for 5 minutes at each dose. Forearm blood flow will be measured by strain gauge plethysmography, blood samples will be obtained to measure t-PA, PAI-1 at each dose. FMD and Radial artery tonometry will also be performed under resting conditions. | Drug: Bradykinin<br>* Patients receive 0, 10, 20, and 40 ng/100cc forearm volume/min of bradykinin intrabrachial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak t-PA release |  | Single Study Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| t-PA release at various doses |  | Single Study Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Transplant, Endothelial Function, Fibrinolysis, Transplant recipients at baseline