Role of intravenous admnistration of Glutathione Sodium Salt in the prevention of reperfusion injury in patients with stemi treated with primary angioplasty. GSH2014 trial

BACKGROUND: Timely recanalization of infarct related artery along with effective myocardial cell reperfusion represents a major challenge in the management of STEMI. The reperfusion of coronary arteries could induce further cardiomyocyte death by generating oxidative stress, which itself can mediate myocardial damage through several different mechanisms. Based on experimental and clinical studies, interventions to treat reperfusion injury by antioxidants were considered to be an appropriate therapeutic option. AIM OF THE STUDY: To explore wheter glutathione sodium salt in addition to standard treatment can reduce oxidative status and consequently improve myocardial microculation reducing infarct related area and ventricular remodeling in consecutive STEMI patients. MATERIALS AND METHODS: 49 patients underwent primary angioplasty and were enrolled in GSH2014 multicenter randomized placebo-controlled trial. Patients were randomized to receive standard therapy plus glutathione sodium salt (2.5 gr ev of /die) or placebo administered before PCI and in the 3 days following the procedure. RESULTS: considering the basal levels in the treated group vs. the placebo occurred: - after revascularization, a significant percentage decrease of intracoronary levels of H202 (-24.7±55.2 vs. 45±97.3 %, p=0.0031), 8-isoPGF2-alfa production (2.3±44.2 vs. 30.6%±44, p=0.028) as well as a statistical increase in HBA (64.6±112.1 vs. 18.5±56.7 %, p=0.072); - on the 5th day after primary angioplasty, a significant decrease in H202 (-38.4±22.3 vs. -2.5±48.4 %, p=0.0015) and 8-isoPGF2-alfa production (-19.5±21.4 vs. 37±120.5 % uM, p=0.028) as well as a statistical increase in NO bioavailability (145.7±111.4 vs. 47.2±100 % uM, p=0.0019) and HBA levels (46.9±28.1 vs. 13.8±54.1 % uM, p=0.009). The intracoronary percentage reduction of 8-isoPGF2-α in the GSH group vs. placebo correlated with the Timi Frame Count post procedure (p = 0.012; R = 0.55); furthemore the percentualdecrease, from peak levels at at the five days, of high-sensitive cardiac troponin T [-21.2±12.7 vs. 12.4±23.1 pg/ml (p=0.00)], were correlated with H202 production (R=0.4, p<0.042). The GSH Group vs. placebo showed a significant increase in patients (54.8 vs. 25%) with BLUSH (≥ 2) post treatment; among them the 12.5% vs. 0% of the placebo group had a BLUSH of 3 (p = 0.04). CONCLUSION: Intravenous GSH infusion improves microcirculatory and cellular perfusion and prevent reperfusion injury. Standard therapy and GSH infusion represents a novel pharmacologic treatment to reduce the estension of myocardial ischemia and to improve prognosis of patients undergoing primary PCI.