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.
Keywords: Hydrogen gas; drug delivery; microbubbles; myocardial ischemia−reperfusion injury; ultrasound imaging.