BACKGROUND: Myocardial reperfusion therapy remains the most effective strategy to limit infarct size and improve clinical outcome. However, reperfusion injury is still inevitable, and a number of strategies have been developed to ameliorate its lethal outcome. The beneficial roles of ischemic postconditioning (Ipost) have regained more interest in targeting myocardial reperfusion phase to improve cardioprotection. AIMS: This study was to determine whether acute or chronic treatment with atorvastatin affects cardioprotection when it was combined with Ipost. RESULTS: Acute or chronic atorvastatin treatment significantly reduced infarct size and recovered contractile dysfunction during reperfusion. When Ipost was combined with atorvastatin treatment, chronic, but not acute, atorvastatin therapy attenuated the cardioprotective effects of Ipost. Chronic, but not acute, atorvastatin treatment also abolished Ipost-induced phosphorylation level of Akt and endothelial nitric oxide synthase (eNOS). CONCLUSIONS: Chronic atorvastatin treatment could interfere with cardioprotective effects of Ipost on limiting infarct size and contractile dysfunction, possibly via inhibition of Akt and eNOS activity. This study suggests that Ipost should be used carefully when atorvastatin is taken by patients with AMI.
BACKGROUND: Myocardial reperfusion therapy remains the most effective strategy to limit infarct size and improve clinical outcome. However, reperfusion injury is still inevitable, and a number of strategies have been developed to ameliorate its lethal outcome. The beneficial roles of ischemic postconditioning (Ipost) have regained more interest in targeting myocardial reperfusion phase to improve cardioprotection. AIMS: This study was to determine whether acute or chronic treatment with atorvastatin affects cardioprotection when it was combined with Ipost. RESULTS: Acute or chronic atorvastatin treatment significantly reduced infarct size and recovered contractile dysfunction during reperfusion. When Ipost was combined with atorvastatin treatment, chronic, but not acute, atorvastatin therapy attenuated the cardioprotective effects of Ipost. Chronic, but not acute, atorvastatin treatment also abolished Ipost-induced phosphorylation level of Akt and endothelial nitric oxide synthase (eNOS). CONCLUSIONS: Chronic atorvastatin treatment could interfere with cardioprotective effects of Ipost on limiting infarct size and contractile dysfunction, possibly via inhibition of Akt and eNOS activity. This study suggests that Ipost should be used carefully when atorvastatin is taken by patients with AMI.
Authors: Ellen N Sutter; Anna E Mattlage; Marghuretta D Bland; Kendra M Cherry-Allen; Elinor Harrison; Swati M Surkar; Jeffrey M Gidday; Ling Chen; Tamara Hershey; Jin-Moo Lee; Catherine E Lang Journal: Transl Stroke Res Date: 2018-08-07 Impact factor: 6.829