Early, successful restoration of myocardial perfusion after a ST-segment elevation myocardial infarction (STEMI) is the most effective way to reduce final infarct size and improve clinical outcome. However, experimental and clinical data have shown that reperfusion per se may have harmful effects, the “myocardial reperfusion injury” is identified as a target for cardioprotection. Molecular hydrogen (H2) is the most lightweight gas and abundant chemical element in the universe. Recent evidence has shown that H2 is a potent antioxidant, antiapoptotic and anti-inflammatory agent and so may have potential medical applications in cells, tissues and organs.
The antioxidant advantages of H2 gas include: a high bio-membrane penetration and intracellular diffusion capability which enable it to reach subcellular compartments like mitochondria; selectively scavenging the deleterious hydroxyl radical while preserving other important reactive oxygen and nitrogen species for normal signaling regulation. The efficacy of molecular H2 for prevention and treatment of various diseases, with underlying pathological conditions of ischemia-reperfusion injury, has been reported by numerous non-clinical and clinical studies.
Preliminary studies have shown that H2 gas inhalation reduced infarct size and mitigated adverse left ventricular (LV) remodeling in a rat model, and a recent phase I clinical study in Japan has shown that H2 inhalation during primary percutaneous coronary interventions (pPCI) is feasible and safe and may also promote LV reverse remodeling.
The HI-STEMI (Inhaled HYdrogen for myocardial preservation in patients with ST-Elevation Myocardial Infarction admitted in the emergency room) project aims to evaluate the efficacy of a H2 inhalation on top of standard care when compared to standard care alone, on LV function and remodeling in reperfused STEMI. The primary efficacy endpoint is the global LV function assessed as ejection fraction (EF) changes from pPCI (day 1) to 6 months later. LV will be evaluated by echocardiography with imaging data independently analyzed in a central core echo lab.
As a secondary outcome, the project aims to estimate the concentration of cardiac troponins, CK-MB/CK, and natriuretic peptides after pPCI; the incidence of ≥70% resolution of ST-segment elevation 1hr after pPCI; early LVEF change at day 4; LV end-diastolic volume at 3 months; MI size by cardiac magnetic resonance at 4 days after pPCI and at 6 months; the rehospitalization rate for cardiovascular reasons; the risk of cardiovascular death, heart failure, and cardiogenic shock at 6 months.
