Glutathione Redox Changes in Pulmonary Arterial Blood After Remote Ischemic Conditioning in Pulmonary Hypertension: A Single-Arm Pilot Study

Oxidative stress contributes to pulmonary hypertension (PH), but acute redox responses within the pulmonary circulation remain poorly characterized. In this prospective, open-label, single-arm pilot study, 15 patients with PH underwent one 50 min session of remote ischemic conditioning (RIC) during right heart catheterization. Pulmonary arterial (PA) blood was collected immediately before and after RIC. The prespecified primary biomarker family comprised reduced glutathione (GSH) response and the oxidized glutathione-to-GSH (GSSG/GSH) ratio in PA blood-cell and plasma fractions. PA blood-cell GSH response increased (mean paired difference, 118; 95% CI, 83-152; Holm-adjusted p < 0.001), whereas the blood-cell GSSG/GSH ratio decreased (-0.64; 95% CI, -0.81 to -0.46; Holm-adjusted p < 0.001). Plasma glutathione measures were not significant after multiplicity adjustment. PA lactate, the prespecified secondary endpoint, decreased by 0.45 mmol/L (95% CI, 0.20-0.71; p = 0.002). All participants completed RIC without clinically evident acute adverse events. These preliminary findings identify acute PA blood-cell glutathione and metabolic changes associated with RIC; however, the single-arm design precludes causal inference, and confirmation in randomized sham-controlled studies is warranted.