Intracoronary Bradykinin Mediated t-PA Release in Heart Transplant Recipients (P1A4D)

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

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).

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• Status: Withdrawn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. 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)
2. 25 Subjects will have transplant vasculopathy and 25 subjects will be free of transplant vasculopathy, as documented in previous angiograms.
3. Otherwise 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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bradykinin; 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; Bradykinin 0, 0.2, 0.6, 2.0 ug/min intracoronary, for 5 minutes at each dose.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): 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 (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Heart Transplant; Fibrinolysis; Resting conditions
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Cysteine Proteinase Inhibitors; Bradykinin; Kininogens
• Other Study ID Numbers: 080823