P137Lack of effect of remote ischemic perconditioning in rats with type 1 diabetes in vivo

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Abstract

Aims: It is well established that preconditioning effectively protects from myocardial ischemia-reperfusion (IR) injury. It has been suggested that co-morbidities including diabetes may impair the cardioprotective effect of preconditioning. More recently also remote ischemic perconditioning (RIPerc), which is a clinically more feasible mode of cardioprotective treatment, has been shown to reduce infarct size. It is not known, however, whether RIPerc is affected by co-morbidities. The objective of this study was to investigate whether signaling mechanisms and the cardioprotective effect of RIPerc are influenced by presence of diabetes.

Methods: The study was performed on non-diabetic and diabetic Sprague-Dawley rats. Diabetes was induced by streptozotocin (55 mg/kg iv) given 4 weeks before IR experiments. The rats were subjected to 30 min left coronary artery ligation followed by 2 h reperfusion with or without RIPerc induced by bilateral femoral artery occlusion for 15 min during the last 15 min of coronary artery occlusion (n=6-7 in all groups).

Results: RIPerc reduced infarct size (expressed in percentage of the area at risk) in non-diabetic rats from 68±2% to 46±4% (P<0.001). This effect was associated with increased expression of phosphorylated (ser 1177) eNOS expression and reduced activity of Rho kinase and arginase. Infarct size in rats with type 1 diabetes subjected to IR was 68±1%. In contrast to control rats, RIPerc did not affect infarct size in type 1 diabetic rats (infarct size 63±2%). Furthermore, expression of phosphorylated eNOS, Rho kinase activity and arginase activity was unaffected by RIPerc in diabetic rats.

Conclusion: RIPerc fails to protect from myocardial IR injury in rats with type 1 diabetes. Furthermore, upstream signaling events contributing to the cardioprotection induced by RIPerc are unaffected in diabetic rats. This finding may have important implications for the efficacy of cardioprotective treatment in diabetes.

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