Brachial Artery t-PA Release in Heart Transplant Recipients (P1A3C)

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)

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.

Study Overview

• Status: Withdrawn
• Conditions: Heart Transplantation
• Intervention / Treatment: Drug: Bradykinin

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Adults 18 years and greater who have undergone heart transplantation
2. Healthy

Exclusion criteria:

1. PVC < 30
2. Hypertensive subjects on ACE inhibitors
3. Pregnant or nursing mothers
4. Diabetic with HbA1C > 7.5 or stigmata of end organ damage (neuropathy, retinopathy, nephropathy, cardiomyopathy)
5. Cholesterol > 30 mg/dL above NCEP accepted level based on cardiac risk.
6. Triglycerides > 200
7. Previously diagnosed obstructive coronary artery disease
8. Renal insufficiency (Creatinine ≥ 1.5 mg/dl)
9. History of cerebrovascular disease
10. Any chronic inflammatory disease (rheumatologic, inflammatory bowel disease, etc)
11. 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).
12. Angiotensin converting enzyme inhibitor use
13. Coagulopathy (INR ≥ 1.5, PTT ≥ 150% of control)
14. Peripheral Vascular Disease
15. Other chronic medical illnesses at the discretion of the investigators

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bradykinin; 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; Patients receive 0, 10, 20, and 40 ng/100cc forearm volume/min of bradykinin intrabrachial.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: James AS Muldowney, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: October 24, 2008
• First Submitted That Met QC Criteria: October 24, 2008
• First Posted (Estimate): October 27, 2008

Study Record Updates

• Last Update Posted (Estimate): July 15, 2016
• Last Update Submitted That Met QC Criteria: July 14, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Endothelial Function; Heart Transplant; Fibrinolysis; Transplant recipients at baseline
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Cysteine Proteinase Inhibitors; Bradykinin; Kininogens
• Other Study ID Numbers: 070517