The purpose of this study is to determine the effect of 6R-BH4 on vascular function in patients with coronary artery disease. We hypothesize that 6R-BH4 will improve vascular function in these patients.

Decreased production of nitric oxide (NO) from the endothelium (the layer of cells that forms the lining of all blood vessels) has been shown to contribute to atherosclerosis. NO has multiple beneficial effects on vascular function. Endothelial function can be measured in humans via a number of methods, and endothelial dysfunction has been shown to be a strong adverse predictor of cardiovascular events and mortality.

Tetrahydrobiopterin (BH4) is essential for the production of NO in endothelial cells. 6R-BH4 is a synthetic version of naturally occurring BH4. We aim to investigate the effects of oral 6R-BH4 supplementation on endothelial function in patients with coronary artery disease.

Inclusion Criteria:

• Multi-vessel coronary artery disease scheduled for coronary artery bypass surgery (CABG)

Exclusion Criteria:

• Inability to provide informed consent
• Female subject who is pregnant, lactating or planning pregnancy during course of study
• Prior clinical diagnosis of heart failure requiring diuretic therapy with evidence of severe left ventricular dysfunction
• Recent acute coronary event (<4 weeks)
• Emergency CABG
• Newly diagnosed diabetes mellitus (<1 month)
• Body weight >130kg
• Impaired renal function (creatinine >180umol/l)
• Elevated liver function tests (ALT >50umol/l or AST >2x normal)
• Pacemakers, ICDs or metallic implants not compatible with MRI scanning
• Subjects receiving experimental medications or participating in another study
• Terminally ill subjects
• Known hypersensitivity to 6R-BH4
• Concomitant treatment with methotrexate, levodopa, PDE-3 or PDE-5 inhibitors