Oxidative stress in patients with pulmonary hypertension

Rationale: Pulmonary arterial hypertension is a devastating cardiovascular disease that is progressive and fatal despite advances in therapy. Animal models have shown that oxidative stress may be pathogenic in pulmonary hypertension. Objectives: We hypothesized that oxidative stress, as measured by increased levels of oxidants, including superoxide, may play a role in pulmonary arterial hypertension in humans. We also hypothesized that oxidants are elevated in patients with pulmonary arterial hypertension compared with normal controls and that they correlate with measures of pulmonary arterial hypertension severity. Methods and Measurements: Using a novel application of electron paramagnetic resonance spectroscopy to measure free radical oxidants, we initially evaluated whether levels of oxidants from whole blood collected from the pulmonary artery obtained during right heart catheterization would correlate with oxidant levels in peripheral venous blood. We then measured oxidants in peripheral venous blood in patients with pulmonary arterial hypertension and normal controls. Main Results: Results showed a significant correlation between oxidant levels in blood collected from the pulmonary artery and peripheral vein but no significant elevation of oxidants in pulmonary hypertension patients versus control subjects. Furthermore, there were no correlations between levels of oxidants and severity of pulmonary arterial hypertension, as assessed by symptoms, functional capacity, hemodynamics, and the REVEAL risk score. Conclusions: Contrary to previous animal studies and indirect measures of oxidative stress, we were unable to confirm an oxidative environment in patients with pulmonary arterial hypertension, at least when assessed by levels of free radical oxidants, such as superoxide, in whole blood via electron paramagnetic resonance spectroscopy.