Naseer Ahmed
The Aga Khan University, Pakistan
Posters & Accepted Abstracts: J Cardiovasc Dis Diagn
Background & Aim: Heart failure followed by ischemiareperfusion injury is a major issue in heart transplantation. During last decade, multiple strategies have been used to control this important problem. It is well-known that fingolimod, a sphingosine 1Phosphate receptor modulator may cause anti-inflammatory, antioxidant and Tlymphocyte depletion leading to lymphopenia. Thus, it leads to a reduction in ischemiareperfusion injury and ultimately, prevention of heart failure. The aim is to investigate the preoperative effect of fingolimod was to evaluate cardioprotective role in heterotopic heart transplantation experimental model in comparison of placebo administration. Method: Male Sprague-Dawley (SD) rats (300-350 g) (n=30) treated with either fingolimod (1 mg/kg total body weight) or normal saline solution. Ischemia was applied for 60 minutes and reperfusion was followed for 24 hours and 1 week. Post heterotopic heart transplantation at 24 hours and 2 weeks all surviving rats were sacrificed. Blood and myocardial tissue were collected for analysis of myocardial biomarkers, inflammatory markers, oxidative stress and signaling pathways. Myocardial fibrosis was investigated using Massonâ??s trichrome staining, Fluorescein Activated Cell Sorting (FACS) to measure Tlymphocyte and TUNAL assay for level of apoptosis. Result: Following 60 minutes of ischemia, both saline treated and vehicle group showed significant myocardial injury following heterotopic heart transplantation. In fingolimod treated group, reduction of inflammation and oxidative stress have been observed significant as compared to salinetreated or vehicle group. FACS analysis showed a significant Tlymphocyte depletion in peripheral blood after fingolimod treatment, which was not observed after saline or vehicle treatment, on TUNAL assay significant reduction in apoptosis has been observed. Conclusion: The longterm survival improved in this study might be due to a cardioprotective role of fingolimod to prevent ischemia reperfusion injury in heterotopic heart transplantation model, which may be mediated by decreased inflammation, reactive oxygen species and the lymphocyte depletion shown in the FACS analysis leading to reduced apoptosis.
E-mail: naseer.ahmad@aku.edu
Cardiovascular Diseases & Diagnosis received 427 citations as per Google Scholar report
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