Protocol Number: 03-H-0312

Title:

Dietary Nitrate/Nitrite as Sources of Bioactive Nitric Oxide in Patients with Coronary Artery Disease

Number:

03-H-0312

Summary:

This study will determine whether dietary nitrates and nitrites can produce nitric oxide in the body and dilate blood vessels in patients with coronary artery disease. Nitric oxide is normally made by endothelial cells that line blood vessels. It plays an important role in maintaining the normal function of arteries by keeping them open and preventing damage from substances such as cholesterol in the blood stream. Coronary artery disease is caused by atherosclerosis (hardening of the arteries or build-up of cholesterol and scar tissue within the walls of the arteries). Once arteries become clogged, the ability of the endothelium to produce nitric oxide diminishes considerably and may speed up the disease process, leading to shortness of breath, chest pain, and an increased risk of heart attack or stroke.

Patients 21 years of age and older with coronary artery disease may be eligible for this study. Participants will have a medical history and physical examination, electrocardiogram (recording of the electrical activity of the heart), echocardiogram (ultrasound test of the heart), treadmill exercise stress test (see below), and will meet with a dietitian. They will be hospitalized at the NIH Clinical Center on two occasions. For 1 week before each admission, they will follow a diet prescribed by an NIH nutritionist. The diet before one admission will be high in nitrates and nitrites, and the diet before the other admission will be low in nitrates and nitrites. Each admission will last 4 days, during which participants will undergo the following tests:

- Forearm blood flow study: Small tubes are placed in the artery and vein at the inside of the elbow of the dominant arm (right- or left-handed) and a small tube is placed in a vein of the other arm. The tubes are used for infusing saline (salt water) and for drawing blood samples. A pressure cuff is placed around the upper part of the dominant arm, and a rubber band device called a strain gauge is also placed around the arm to measure blood flow. When the cuff is inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow. Maximum grip-strength of the dominant arm is measured with a dynamometer. Forearm blood flow is measured and blood samples are drawn at the following times: 20 minutes after the tubes are placed; during a hand-grip exercise; and 4 minutes after the exercise is completed.

- Brachial artery reactivity study: This test measures how well the patient's arteries widen. For the procedure, the patient rests on a bed for 30 minutes. An ultrasound measuring instrument is then placed over the artery just above the elbow. The artery size and the flow of blood through it are measured before and after a pressure cuff around the forearm is inflated. Fifteen minutes later, the same measurements are taken before and 3 minutes after a nitroglycerin tablet is placed under the patient's tongue.

Treadmill exercise testing: Patients exercise on a treadmill until they experience chest pain, shortness of breath, or tiredness. The patient's heart rhythm is monitored continuously and blood pressure is measured every 3 minutes. A nurse and doctor are in attendance throughout the study.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Adults older than 21 years.

Coronary artery disease established by angiography.

No myocardial infarction within 1 month.

Left ventricular ejection fraction greater than 30%.

No congestive heart failure symptoms within 2 months.

Subject provides written, informed consent.

EXCLUSION CRITERIA:

Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography.

Subject physically unable to perform treadmill exercise due to neurologic or orthopedic conditions.

Hypersensitivity to organ nitrates.

Insulin-dependant diabetes mellitus.

Coumadin therapy (because of vitamin K content of green leafy vegetables).

Women of childbearing age unless recent pregnancy test is negative.

Lactating women.

Unwillingness to adhere to dietary requirements or allergy to necessary components of diets, as determined during interview by the dietician.

Surgical or disease-related diminished acid secretion.

Significant non-cardiac disease.

Special Instructions: Currently Not Provided

Keywords:

Endothelium

Atherosclerosis

Vasodilation

Ischemia

Exercise

Recruitment Keywords:

Coronary Artery Disease

CAD

Conditions:

Coronary Arteriosclerosis

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6.

Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6.

Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664-6.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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