Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model
During heart transplantation, donor heart leads to reduced oxygen supply resulting in low level of high energy phosphate (HEP) reserves in cardiomyocyte. Lower HEP is one of the underlying reasons of cell death due to ischemia. In this study we investigated the role of Fingolimod (FTY720) in heart t...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6548 |
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| author | Naseer Ahmed Javeria Farooq Soban Sadiq Sultan Ayoub Meo Azam Jan Faisal H. Cheema Giuseppe Faggian Alessio Rungatscher |
| author_facet | Naseer Ahmed Javeria Farooq Soban Sadiq Sultan Ayoub Meo Azam Jan Faisal H. Cheema Giuseppe Faggian Alessio Rungatscher |
| author_sort | Naseer Ahmed |
| collection | DOAJ |
| description | During heart transplantation, donor heart leads to reduced oxygen supply resulting in low level of high energy phosphate (HEP) reserves in cardiomyocyte. Lower HEP is one of the underlying reasons of cell death due to ischemia. In this study we investigated the role of Fingolimod (FTY720) in heart transplantation ischemia. Eight groups of Sprague-Dawley rats (<i>n</i> = 5 for each subgroup) were made, A1 and C1 were given FTY720 1 mg/kg while B1 and D1 were given normal saline. The hearts were implanted into another set of similar rats after preservation period of 1 h at 4–8 °C. Significantly higher Left ventricular systolic pressure (LVSP), dP/dT maximum (<i>p</i> < 0.05), dP/dT minimum (<i>p</i> < 0.05) were recorded in the FTY720 treated group after 24 h of reperfusion while after 1 h of reperfusion, there were no significant differences in LVSP, maximum and negative dP/dT, and Left ventricular end diastolic pressure (LVEDP) between the control and the FTY720-treated transplant groups. Coronary blood flow (CBF) was enhanced (<i>p</i> < 0.05) in the FTY720 treated group after 1 and 24 h. ATP <i>p</i> < 0.001, <i>p</i> < 0.05 at 1 and 24 h, ADP <i>p</i> < 0.001, <i>p</i> > 0.05 at 1 and 24 h, and phosphocreatine <i>p</i> < 0.05, <i>p</i> > 0.05 at 1 and 24 h were better preserved by FTY720 treatment as compared to control group. The study concluded that pretreatment of grafted hearts with FTY720 improved hemodynamics, CBF, high energy phosphate reserves, reduces the peroxynitrite level and poly (ADP ribose) polymerase (PARP) inhibition that prevents ischemia-reperfusion injury. |
| first_indexed | 2024-03-10T16:30:22Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:30:22Z |
| publishDate | 2020-09-01 |
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| spelling | doaj.art-119677edc40145f886f6d5c99648aefa2023-11-20T12:54:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118654810.3390/ijms21186548Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation ModelNaseer Ahmed0Javeria Farooq1Soban Sadiq2Sultan Ayoub Meo3Azam Jan4Faisal H. Cheema5Giuseppe Faggian6Alessio Rungatscher7Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi 74800, PakistanDepartment of Biological and Biomedical Sciences, The Aga Khan University, Karachi 74800, PakistanFaculty of Medicine, Imperial College London, London SW72AZ, UKDepartment of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi ArabiaDepartment of Cardiac Surgery, Rehman Medical Institute, Peshawar 25000, PakistanDepartment of Biomedical Sciences, University of Houston College of Medicine, Houston, TX 77004, USADepartment of Surgery, Cardiac Surgery Division, University of Verona Medical School, 37129 Verona, ItalyDepartment of Surgery, Cardiac Surgery Division, University of Verona Medical School, 37129 Verona, ItalyDuring heart transplantation, donor heart leads to reduced oxygen supply resulting in low level of high energy phosphate (HEP) reserves in cardiomyocyte. Lower HEP is one of the underlying reasons of cell death due to ischemia. In this study we investigated the role of Fingolimod (FTY720) in heart transplantation ischemia. Eight groups of Sprague-Dawley rats (<i>n</i> = 5 for each subgroup) were made, A1 and C1 were given FTY720 1 mg/kg while B1 and D1 were given normal saline. The hearts were implanted into another set of similar rats after preservation period of 1 h at 4–8 °C. Significantly higher Left ventricular systolic pressure (LVSP), dP/dT maximum (<i>p</i> < 0.05), dP/dT minimum (<i>p</i> < 0.05) were recorded in the FTY720 treated group after 24 h of reperfusion while after 1 h of reperfusion, there were no significant differences in LVSP, maximum and negative dP/dT, and Left ventricular end diastolic pressure (LVEDP) between the control and the FTY720-treated transplant groups. Coronary blood flow (CBF) was enhanced (<i>p</i> < 0.05) in the FTY720 treated group after 1 and 24 h. ATP <i>p</i> < 0.001, <i>p</i> < 0.05 at 1 and 24 h, ADP <i>p</i> < 0.001, <i>p</i> > 0.05 at 1 and 24 h, and phosphocreatine <i>p</i> < 0.05, <i>p</i> > 0.05 at 1 and 24 h were better preserved by FTY720 treatment as compared to control group. The study concluded that pretreatment of grafted hearts with FTY720 improved hemodynamics, CBF, high energy phosphate reserves, reduces the peroxynitrite level and poly (ADP ribose) polymerase (PARP) inhibition that prevents ischemia-reperfusion injury.https://www.mdpi.com/1422-0067/21/18/6548fingolimod (FTY720)cardiac functioncoronary blood flowhigh energy phosphatespoly (ADP ribose) polymerase |
| spellingShingle | Naseer Ahmed Javeria Farooq Soban Sadiq Sultan Ayoub Meo Azam Jan Faisal H. Cheema Giuseppe Faggian Alessio Rungatscher Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model International Journal of Molecular Sciences fingolimod (FTY720) cardiac function coronary blood flow high energy phosphates poly (ADP ribose) polymerase |
| title | Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model |
| title_full | Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model |
| title_fullStr | Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model |
| title_full_unstemmed | Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model |
| title_short | Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model |
| title_sort | fingolimod fty720 preserves high energy phosphates and improves cardiac function in heterotopic heart transplantation model |
| topic | fingolimod (FTY720) cardiac function coronary blood flow high energy phosphates poly (ADP ribose) polymerase |
| url | https://www.mdpi.com/1422-0067/21/18/6548 |
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