Image-Guided Hydrogen Gas Delivery for Protection from Myocardial Ischemia-Reperfusion Injury via Microbubbles

Cardiomyocyte death induced by ischemia-reperfusion is a major cause of morbidity and mortality worldwide. Hydrogen (H₂), as an antioxidant, has been shown to have great potential in preventive and therapeutic applications against lethal injury that occurs from ischemia-reperfusion. However, H₂ is sparingly soluble in water, resulting in its poor bioavailability in blood and damaged tissues. Here, we have developed an ultrasound-visible H₂ delivery system by loading H₂ inside microbubbles (H₂-MBs) to prevent myocardial ischemia-reperfusion injury. Using this system, the concentration of H₂ in unit volume can be greatly improved under normal temperature and pressure conditions. H₂-MBs can be visually tracked with ultrasound imaging systems and can effectively release their therapeutic gas. In vivo systemic delivery of H₂-MBs in myocardial ischemic rats at the start of reperfusion resulted in a significant reduction of infarct size and pathological remodeling. Further analysis showed that this approach markedly inhibited cardiomyocyte apoptosis and reduced myocardial inflammation and oxidant damage in myocardial ischemia-reperfusion rats. These results indicate that H₂-MBs are a promising visual delivery system for H₂-based therapeutic applications.