Abstract
Background: Oxidative stress has been linked to heart failure (HF) in humans. Antioxidant-based treatments are not always effective. Hence, we tested a hypothesis that some patients with heart failure may have a hyper-reductive state. Identifying this condition may lead to personalized optimization and better outcomes. Methods: Blood samples were collected from age and sex matched healthy control (n=50) and HF patients (n=55). Serum was separated and stored immediately in -80°C until analysis. Reduced glutathione (GSH) and its redox ratio (GSH/GSSG) using sigma GSH kit (38185) and malondialdehyde (MDA) levels by HPLC in the serum of HF patients were quantified. Further, the activities of key antioxidant enzymes including catalase, SOD, glutathione peroxidase and glutathione reductase were analyzed using a kinetic spectrophotometer. Results: While majority of the HF patients had significantly decreased the glutathione redox status (GSH/GSSG) and increased MDA levels (lipid peroxidation index) indicating a hyper-oxidative state, a subset of HF patients (n=8) displayed a significantly increased GSH/GSSG ratio along with decreased MDA levels in the serum, suggesting a strong association for a hyper-reductive state in the development of HF. Moreover, closer analyses of echocardiography revealed a lower ejection fraction (EF) with substantial diastolic dysfunction (MV E/A) in the HF patients with hyper-reductive state. Conclusion: These results suggest that hyper-reductive condition may indicate a worsening clinical course for HF patients. Thus a thorough diagnosis of redox state and personalized approach for antioxidant treatment is warranted.
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