title: Vascular calcification abrogates the nicorandil mediated cardio-protection in ischemia reperfusion injury of rat heart.
abstract: The present study was aimed to determine the efficacy of nicorandil in treating cardiac reperfusion injury with an underlying co-morbidity of vascular calcification (VC). Adenine diet was used to induce VC in Wistar rat and the heart was isolated to induce global ischemia reperfusion (IR) by Langendorff method, with and without the nicorandil (7.5mg/kg) pre-treatment and compared with those fed on normal diet. The adenine-treated rats displayed abnormal ECG changes and altered mitochondrial integrity compared to a normal rat heart. These hearts, when subjected to IR increased the infarct size, cardiac injury (measured by lactate dehydrogenase and creatine kinase activity in the coronary perfusate) and significantly altered the hemodynamics compared to the normal perfused heart. Nicorandil pretreatment in rat fed on normal diet enhanced the hemodynamics significantly (P<0.05) along with a substantial reduction in the mitochondrial dysfunction (measured by high ADP to oxygen consumption ratio, respiratory control ratio, enzyme activities and less swelling behavior) when subjected to IR. However, this cardio-protective effect of nicorandil was absent in rat heart with underlying calcification. Our results suggest that, the protective effect of nicorandil, a known mitochondrial ATP linked K+channel opener, against myocardial reperfusion injury was confined to normal rat heart.
authors.affiliation: Vascular Biology Lab, SASTRA University, Thanjavur 613401, India.
authors.forename: Sriram
authors.initials: S
authors.lastname: Ravindran
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Jeyashri
authors.initials: J
authors.lastname: Murali
authors.affiliation: School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Amirthalingam
authors.affiliation: Thanjavur Medical College, Thanjavur 613004, India.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Gopalakrishnan
authors.affiliation: Vascular Biology Lab, SASTRA University, Thanjavur 613401, India. Electronic address: kurian@scbt.sastra.edu.
authors.forename: Gino A
authors.initials: GA
authors.lastname: Kurian
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D000067268:Isolated Heart Preparation; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020108:Nicorandil / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D017208:Rats, Wistar; D061205:Vascular Calcification / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil
keywords: Adenine (PubChem CID: 190); Langendorff perfused heart; Mitochondria; Myocardial ischemia-reperfusion; Nicorandil (PubChem CID: 47528); Vascular calcification