The Role of Nitrite in Preconditioning Mediated Tolerance to Ischemic Stress

INCLUSION CRITERIA: Subjects must be 18-45 years of age. Subject must be in good health. Subjects must provide informed, written consent for participation in this study. Female subjects of childbearing age must have a negative pregnancy test. EXCLUSION CRITERIA: Subjects with a history of cardiac, pulmonary, peripheral vascular, or mitochondrial disease or diabetes mellitus. Subjects with a history or evidence of present or past hypertension (blood pressure greater than 140/90 mmHg), hypercholesterolemia (LDL cholesterol greater than 160 mg/dL). Subjects with abnormal EKG other than sinus bradycardia. Subjects who have a history of smoking within three months. Subjects with anemia (defined as hemoglobin less than 9 g/dL). BMI greater than 30. Subjects with a history of reaction to a medication or other substance characterized by dyspnea and cyanosis will not participate in this study. Subjects with G6PD deficiency. Subjects with a baseline methemoglobin level greater than 1.5%. Lactating females who are breastfeeding, will not participate since nitrite crosses into breast milk and could cause methemoglobinemia in the infant. No volunteer subject will be allowed to take any prescription medication (oral contraceptive agents are allowed). Vitamin supplements, herbal preparations, nutriceuticals or other 'alternative therapies' must be stopped for two weeks prior to study and aspirin, tylenol and NSAIDs must also be discontinued two weeks prior to study. Subjects with a blood pressure of less than 90/60 mmHg or mean arterial pressure (MAP) less than 70 mmHg on the study day will be excluded from the protocol. Positive for HIV or hepatitis A or B or positive for syphilis. Subjects with a history of placement or insertion of any metal devices including pacemakers, cardiac defibrillators, cochlear implants, aneurysm clips, neural stimulators, insulin pumps or foreign bodies, such as, metal shavings will be excluded from participation in the MRS. Subjects with a history of claustrophobia or an inability to lie on their backs will be excluded from the MRS sub-study.