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Comparison of cardioprotective efficacy resulting from a combination of atorvastatin and ischaemic post‐conditioning in diabetic and non‐diabetic rats
Author(s) -
Fan Ying,
Yang Shusen,
Zhang Xiukun,
Cao Yang,
Huang Yonglin
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12014
Subject(s) - atorvastatin , medicine , enos , statin , diabetes mellitus , protein kinase b , ischemia , endocrinology , nitric oxide , cardiology , nitric oxide synthase , apoptosis , chemistry , biochemistry
Summary The aim of the present study was to investigate whether the combination of acute or chronic atorvastatin treatment with ischaemic post‐conditioning ( IP ost) 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 IP ost; (iii) acute statin treatment (50 μmol/L atorvastatin during reperfusion) without IP ost; (iv) acute statin treatment plus IP ost; (v) chronic statin treatment (10 mg/kg atorvastatin per day for 2 weeks) without IP ost; and (vi) chronic statin treatment plus IP ost. 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, IP ost did not limit infarct size or recover contractile dysfunction. Acute atorvastatin treatment with IP ost 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 IP ost 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 IP ost had a greater protective effect within hearts from diabetic rats, but chronic statin treatment with IP ost 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.