Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo |
| |
| Authors: | R Huhn A Heinen MW Hollmann W Schlack B Preckel NC Weber |
| |
| Institution: | 1. Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha 410078, PR China;2. Department of Biochemistry and Molecular Biology, Changsha Medical College, Changsha 410219, PR China;3. Shaoyang Municipal Center for Disease Control and Prevention, Shaoyang 422000, PR China;1. Service d''Hématologie clinique et de Thérapie cellulaire, Bordeaux, Pessac, France;2. Service d''Hématologie, Institut Paoli-Calmettes, Marseille, France;3. Service d''Immuno-Hématologie, Hôpital Robert Debré, Paris, France;4. Service d''Hématologie, Hôpital de l''Hôtel-Dieu, Nantes, France;5. Service de Greffe de Moelle, Hôpital Saint-Louis, Paris, France;6. Service d''Immuno-Hématologie, Hôpital Saint-Louis, Paris, France;1. Institute of Immunology PLA & Department of Immunology, Third Military Medical University, Chongqing 400038, China;2. Function Center, North Sichuan Medical College, Nanchong 637100, Sichuan, China;3. Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China;4. Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400038, China;1. Unidad de Investigación, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;2. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain;3. Laboratorio Central, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;4. Centro para la Investigación Biomédica de Canarias, Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;5. Servicio de Nefrología, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain;1. Department of Cardiology, Hospital Universitari i Politècnic La Fe, Valencia, Spain;2. Department of Phsyiology, Hospital Universitari i Politècnic La Fe, Valencia, Spain;3. Research Center, Hospital Universitari i Politècnic La Fe, Valencia, Spain;4. Department of Cardiovascular Surgery, Hospital Universitari i Politècnic La Fe, Valencia, Spain;1. Departments of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA;2. Department of Experimental Oncology, Cross Cancer Institute, Edmonton, Canada;3. Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas, USA |
| |
| Abstract: | Background and aimsHyperglycaemia blocks sevoflurane-induced postconditioning, and cardioprotection in hyperglycaemic myocardium can be restored by inhibition of the mitochondrial permeability transition pore (mPTP). We investigated whether sevoflurane-induced postconditioning is also blocked in the prediabetic heart and if so, whether cardioprotection could be restored by inhibiting mPTP.Methods and resultsZucker lean (ZL) and Zucker obese (ZO) rats were assigned to one of seven groups. Animals underwent 25 min of ischaemia and 120 min of reperfusion. Control (ZL-/ZO Con) animals were not further treated. postconditioning groups (ZL-/ZO Sevo-post) received sevoflurane for 5 min starting 1 min prior to the onset of reperfusion. The mPTP inhibitor cyclosporine A (CsA) was administered intravenously in a concentration of 5 (ZO CsA and ZO CsA + Sevo-post) or 10 mg/kg (ZO CsA10 + Sevo-post) 5 min before the onset of reperfusion. At the end of reperfusion, infarct sizes were measured by TTC staining. Blood samples were collected to measure plasma levels of insulin, cholesterol and triglycerides.Sevoflurane postconditioning reduced infarct size in ZL rats to 35 ± 12% (p < 0.05 vs. ZL Con: 60 ± 6%). In ZO rats sevoflurane postconditioning was abolished (ZO Sevo-post: 59 ± 12%, n.s. vs. ZO Con: 58 ± 6%). 5 mg and 10 mg CsA could not restore cardioprotection (ZO CsA + Sevo-post: 59 ± 7%, ZO CsA10 + Sevo-post: 57 ± 14%; n.s. vs. ZO Con). In ZO rats insulin, cholesterol and triglyceride levels were significant higher than in ZL rats (all p < 0.05).ConclusionInhibition of mPTP with CsA failed to restore cardioprotection in the prediabetic but normoglycaemic heart of Zucker obese rats in vivo. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
