title: Comparison of cardioprotective efficacy resulting from a combination of atorvastatin and ischaemic post-conditioning in diabetic and non-diabetic rats.
abstract: The aim of the present study was to investigate whether the combination of acute or chronic atorvastatin treatment with ischaemic post-conditioning (IPost) exerts differential effects within the hearts of diabetic and non-diabetic rats. Diabetic and non-diabetic rats were randomly assigned to one of six groups: (i) a non-conditioned group; (ii) a group subjected to IPost; (iii) acute statin treatment (50 μmol/L atorvastatin during reperfusion) without IPost; (iv) acute statin treatment plus IPost; (v) chronic statin treatment (10 mg/kg atorvastatin per day for 2 weeks) without IPost; and (vi) chronic statin treatment plus IPost. The hearts from rats in each group were subjected to 30 min global ischaemia, followed by 120 min reperfusion. Infarct size, haemodynamics and Akt and endothelial nitric oxide synthase (eNOS) expression were examined. In hearts from diabetic rats, IPost did not limit infarct size or recover contractile dysfunction. Acute atorvastatin treatment with IPost limited infarct size and recovered contractile dysfunction in hearts from both diabetic and non-diabetic rats and further activated Akt and eNOS signalling pathways to enhance these protective effects in hearts from diabetic rats. Chronic statin treatment with IPost neither reduced infarct size nor increased recovery of myocardial dysfunction in hearts from both diabetic and non-diabetic rats; this may be associated with inhibition of Akt and eNOS phosphorylation. The combination of acute atorvastatin treatment with IPost had a greater protective effect within hearts from diabetic rats, but chronic statin treatment with IPost failed to protect against reperfusion injury in hearts from either diabetic or non-diabetic rats. These findings will be important for the design of future clinical investigations.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China. fanying1@medmail.com.cn
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Shusen
authors.initials: S
authors.lastname: Yang
authors.forename: Xiukun
authors.initials: X
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt