Intracoronary Bradykinin Mediated t-PA Release in Heart Transplant Recipients

Study Overview
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Brief Summary
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Heart transplant recipients do not have nerves to their hearts. This protocol tests the hypothesis that bradykinin mediated t-PA release in the coronary arteries will be reduced in heart transplant recipients compared to healthy subjects. This study will compare heart transplant recipients to healthy controls who are undergoing cardiac cath for standard of care purposes (separate protocol) and compare the coronary arteries to the forearm in transplant recipients (separate protocol) and healthy controls (separate protocol).

Official Title
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The Effects of Cardiac Innervation on Intra-coronary t-PA Release

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: Heart transplant recipients undergoing annual cardiac catheterization who have participated our protocol: 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). (IRB # 070517) 25 Subjects will have transplant vasculopathy and 25 subjects will be free of transplant vasculopathy, as documented in previous angiograms. Otherwise 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 Healthy controls are being enrolled in SCCOR Project 1, Aims 3A and 3B (IRB# 030473 and 061160) and will not be participating under this IRB number.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bradykinin<br>Patients have holter monitoring. Patients receive intracoronary bradykinin (0.2, 0.6, 2.0 ug/min) and have coronary sinus and coronary artery blood sampling for t-PA and O2 content. | Drug: Bradykinin<br>* Bradykinin 0, 0.2, 0.6, 2.0 ug/min intracoronary, for 5 minutes at each dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-PA release in the coronary artery bed. |  | Single Study Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate variability |  | Single study visit | 
| Histopathology for arteriolar t-PA and sympathetic neurons |  | Single Study Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Transplant, Fibrinolysis, Resting conditions