Remote periconditioning reduces myocardial no-reflow by the activation of K ATP channel via inhibition of Rho-kinase

Abstract

Remote periconditioning is induced by brief cycles of ischemia and reperfusion of a remote organ applied during sustained myocardial ischemia. It remains unknown whether the remote periconditioning reduces myocardial no-reflow. The adenosine triphosphate-sensitive potassium (K ATP) channel opening and inhibition of Rho-kinase may be the important mechanism of protection against myocardial no-reflow. Therefore, this study was sought to assess the effect of remote periconditioning on myocardial no-reflow and explore the possible mechanism. Methods Coronary ligation area and area of no-reflow were determined with pathological means in 58 mini-swines randomized into 7 study groups: 9 controls, 8 in remote periconditioning, 8 in hydroxyfasudil (a specific inhibitor of Rho-kinase)-treated, 9 in glibenclamide (K ATP channel blocker)-treated, 8 in remote periconditioning and glibenclamide, 8 in hydroxyfasudil and glibenclamide and 8 sham-operated. The ischemia and reperfusion model was created with 3 h of left anterior descending artery occlusion followed by 2 h of reperfusion. Results Compared with the control group, remote periconditioning decreased Rho-kinase activity ( P < 0.01), increased coronary blood volume ( P < 0.05), decreased area of no-reflow (from 82.3 ± 3.9% to 45.5 ± 5.7% of ligation area, P < 0.01) and reduced necrosis size (from 98.5 ± 1.3% to 74.7 ± 6.3% of ligation area, P < 0.05). Hydroxyfasudil had the same effect on the above parameters as remote periconditioning. Glibenclamide abrogated the effect of remote periconditioning or hydroxyfasudil on area of no-reflow and necrosis area, but not Rho-kinase activity. Conclusion Remote periconditioning can reduce myocardial no-reflow after ischemia and reperfusion. This beneficial effect could be due to its activation of K ATP channel via inhibition of Rho-kinase.