Abstract 4366427: Sphingosine-1-Phosphate Treatment Optimizes Cardiolipin Profile in Transplanted Right Ventricular Murine Myocardium

Abstract

Background: The success of cardiac transplant is limited by ischemia reperfusion injury and resultant primary graft dysfunction which can be right, left, or biventricular. Few studies focus solely on right ventricular dysfunction. Ex vivo heart perfusion (EVHP) is a novel, alternative preservation strategy to the current standard, cold static preservation (CSP). Our group has defined EVHP with hypothermic, acellular perfusate containing the sphingolipid, sphingosine-1 phosphate (S1P), as superior to CSP at promoting post-transplant cardiomyocyte mitochondrial function and resultant ventricular performance. The effects of EVHP with S1P treatment on recipient lipidomic profiles post-transplantation remains undefined. Hypothesis: Unique lipidomic profiles will exist for transplanted right ventricular murine myocardium compared to healthy controls. S1P treatment will improve lipidomic derangements associated with cardiac transplant. Methods: Wild-type C57BL/6 murine hearts were explanted and stratified by 90-minute preservation method: no-transplant control (Group 1), CSP (Group 2), EHVP (Group 3), and EVHP with 1 μM S1P treatment (Group 4). Group 2-4 hearts were heterotopically transplanted onto the cervical vessels of recipient mice for 120-minutes of reperfusion prior to assessment of right ventricular myocardium by mass spectrometry. Results: Groups 2-4 demonstrated significant differences from controls in lipid profile across several key groups. Specifically, levels of many acylcarnitines, cardiolipins, and sphingomyelins decreased in groups 2-3 compared to group 1 controls. Compared to groups 2-3, group 4 tissues had higher levels of many linoleic acid containing cardiolipins and lower levels of most docosahexaenoic acid containing cardiolipins (Table 1). Conclusion: Ischemia and reperfusion injury in cardiac transplant alters the lipid profile of right ventricular myocardium in mice. Depletion of linoleic acid containing cardiolipins and accumulation of docosahexaenoic acid containing cardiolipins is associated with mitochondrial dysfunction and metabolic syndrome. S1P treatment increases linoleic acid containing cardiolipins and decreases docosahexaenoic acid containing cardiolipins which may be beneficial for mitochondrial function in cardiac transplant.