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Protocol Number: 05-H-0088 
Healthy volunteers between 21 and 40 years of age may be eligible for this study. They must be non-smokers and have no history of high blood pressure, high cholesterol, or diabetes. Candidates are screened with a medical history, physical examination, electrocardiogram, and blood tests. This study is either done in the NIH Clinical Center intensive care unit or on the general clinical ward. Participants are enrolled in Part A of the study. After completion of Part A participants will be enrolled in Part B of the study. Part A: Participants lie in a reclining chair during the study. Small catheters (plastic tubes) are inserted into an artery and vein in the forearm. Another tube is placed in the vein of the opposite arm. Blood pressure cuffs are placed around the upper arm and wrist, and a strain gauge (a rubber band-like device) is placed around the forearm. This device helps us to measure blood flow through the arm. When the blood pressure cuffs are inflated, blood flows into the forearm, stretching the strain gauge at a rate proportional to the blood flow. Pressure cuffs and a strain gauge are also placed on the other arm. After 20 minutes, blood pressure and blood flow are measured in both forearms. Then blood is drawn from the tube in the right vein to measure blood counts, proteins, and other chemicals. Participants then are given small doses of either saline, ascorbic acid, or a medicine called oxypurinol, a form of a drug that is often taken to prevent gout. After 30 minutes, sodium nitrite is injected in increasing doses into the artery for 30 minutes. Blood flow is measured and blood is drawn every 5 minutes during the infusion. At the end of the 30 minutes, blood is drawn from the vein every 30 minutes for 3 hours. After 3 hours, sodium nitrite infusions are restarted for 2 hours and blood flow is measured and samples collected every 30 minutes during this period. Part B: Participants lie in a reclining chair during the study. A small catheter (plastic tube) is placed in the artery of the left forearm to draw blood samples. A larger catheter called a central line is placed in a deeper vein in the neck. Another tube is advanced through the central line into the chambers of the heart, through the heart valve, and into the lung artery to measure pressures in the heart and lungs. Blood is drawn after 30 minutes to obtain baseline measurements. Then saline (sterile salt water) is put into the tube in the lung artery. Blood pressure cuffs are placed around the upper arm and wrist, and a strain gauge (a rubber band-like device) is placed around the forearm, which helps us to measure flow through the arm. When the cuffs are inflated, blood flows into the forearm, stretching the strain gauge at a rate proportional to the blood flow. Pressure cuffs and a strain gauge are also placed on the other arm. After 20 minutes, blood pressure and blood flow are measured in the forearm and blood samples are drawn from the tube in the left artery to measure blood counts, proteins, and other chemicals. Subjects then breathe a mixture of oxygen and nitrogen through a facemask for 30 minutes, then room air for 30 minutes, and then the oxygen and nitrogen mixture for another 30 minutes. While breathing the mixture the second time, sodium nitrite is injected through the tube in the artery in three increasing doses for 5 minutes each. Every 5 minutes during the infusion blood is drawn from the tubes in the neck. Forearm blood flow is also measured every 5 minutes. After 30 minutes, the subject breathes room air for 3 hours and 15 minutes and then the sodium nitrite is injected again in three increasing doses for 5 minutes each. Every 5 minutes during the infusion blood is taken from the tube in the neck and forearm blood flow is measured
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National Institutes of Health Clinical Center