The objective of this proposal is to examine a novel technique called improved Synchronization ModulationElectric Field (i-SMEF) in the protection of donor hearts and improvement of transplanted graft functions. We willapply the i-SMEF on donor hearts during static cold storage and evaluate the transplanted graft function followingheart transplantation in mice. Heart transplantation (HTx) remains the best therapeutic option for advanced-stage heart failure, as well asfor complex congenital heart disease, restrictive cardiomyopathy, and some infectious diseases. However, thelong-term survival rate of the heart graft has only shown a small improvement during the past decades, with amedian survival about 12.5 years. In addition, the maximal time for static cold storage is usually about 5 hours.Longer storage time is associated with higher rates of both early and late graft failure. The development of newstrategy for extension of storage time thereby increasing the donor pool and improvement of the transplantedgraft function are unmet needs. One of the prominent challenges in HTx is ischemia reperfusion injury (IRI) to the graft. IRI is a major factorfor both early and late graft failure and mortality. Following hypoxia, due to poor ATP supply, activity of theNa+/K+-ATPase (Na/K pump) slows down or stops, which is one of the earliest and critical impairments followingischemia. Reduction in the Na/K pump function disrupts the equilibrium of cellular ion concentrations, cell volumeand membrane potential, which can cause damage to all cellular components (e.g., mitochondria), apoptosisand necrosis. Therefore, maintaining the Na/K pump function following ischemia could be a vital initial strategyfor the protection or prevention of the ischemic injury. We have developed a novel technique, named the i-SMEF (patent pending, Chen and Liu), which can notonly maintain the pump functions, but also generate ATP molecules. Based on strong preliminary findings, we propose to test this technique in a mouse HTx model. We will testour hypothesis that application of the i-SMEF on donor hearts during cold storage protects against ischemicinjury and improves the transplanted graft functions.
Public Health Relevance Statement: The objective of this proposal is to examine a novel technique called improved Synchronization Modulation
Electric Field (i-SMEF) in the protection of donor hearts and improvement of transplanted graft functions. We will
apply the i-SMEF on donor hearts during static cold storage and evaluate the transplanted graft function following
heart transplantation in mice.
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