O2 Transport and Utilization in Health and Lung Disease

Role of Nitric Oxide Coupling in Muscle Dysfunction With COPD

Skeletal muscle dysfunction is a frequent and clinically relevant systemic manifestation of Chronic Pulmonary Obstructive Disease (COPD), which is still poorly understood. Therefore, the focus of this study is on the role of a deficit in tetrahydrobiopterin and nitric oxide synthase uncoupling induced by chronic oxidative stress on metabolic and vascular abnormalities in skeletal muscle of patients suffering from COPD.

The purpose of this study is to assess the efficacy of supplementation with tetrahydrobiopterin (BH4) for improving vascular and muscle function in patients with COPD and healthy controls.

Inclusion Criteria:

• All subjects must be between the age of 18 and 85 years;
• For the COPD cohort, patients with a diagnosis of stable COPD (i.e., those not experiencing an acute exacerbation of symptoms) and spirometric evidence of airway obstruction (FEV1 <80% predicted, FEV/FVC<0.70);
• Ability to perform motor tests;
• Ability to provide informed consent

Exclusion Criteria:

• uncontrolled hypertension;
• hyperlipidemia;
• recent exacerbation;
• Major cardiovascular event procedure (<3 months);
• Pregnancy
• known significant hepatic, renal disease, active substance abuse
• contraindication to MRI, claustrophobia