Perfusion of a heart involves forcing blood or fluid through the organ. A recent study shows that perfusing a heart with MitoQ, an antioxidant targeted to treat mitochondria, before transplantation may block inflammation brought on by oxidative damage from ischemia-reperfusion injury. Researchers at the University of Cambridge and the National Institute for Health Research Cambridge Biomedical Research Center experimented with this technique using mice and identified major benefits in preventing free radical damage during transplantation.
The findings suggest that MitoQ could be essential in ensuring successful heart transplants.
“Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction,” wrote Anna J. Dare, MBBCh, PhD, in the article, “The Mitochondria-Targeted Anti-Oxidant MitoQ Decreases Ischemia-Reperfusion Injury in a Murine Syngeneic Heart Transplant Model.”
When a heart is taken from a donor, it is kept in cold storage until it can be transplanted into a recipient — typically a patient with cardiac failure. During the time of cold storage, the heart is deprived of oxygen. For every hour the heart is deprived of oxygen past the fourth hour of storage, the risk for primary graft failure (PGF) increases by 43% as a result of possible IR injury. Considering the heavy burden placed already on the organ donor list, it is important to ensure transplanted hearts are protected from IR injury.
During the study, the research team flushed mouse hearts with one of three solutions: storage solution, storage solution with MitoQ, or storage solution with decyltriphenylphosphonium, a non-oxidant negative control molecule. The hearts were then placed in cold storage for 30 minutes or four hours. Finally, the hearts were transplanted into another set of mice, which were analyzed for beating score, inflammatory markers, and cardiac oxidative damage.
Looking at the results, the team determined that MitoQ is able to prevent IR injury. Hearts perfused with MitoQ experienced less oxidative damage than those perfused with the negative control, decyltriphenylphosphonium. This correlated into less inflammation early after transplantation and a higher beat score. Whereas thirty minutes of cold storage did not affect graft beat score, four hours significantly reduced the score; these results were reversed by MitoQ but not by either negative control.
“Together, our data show that increased mitochondrial oxidative damage is a major contributor to poor graft outcome in the early post-transplant period and that this can be prevented by MitoQ,” wrote Dr. Dare. It may be good practice to perfuse hearts with MitoQ before cold storage, but additional tests are necessary before this can become an accepted standard practice.