title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jing-Lin
authors.initials: JL
authors.lastname: Zhao
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Pei
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Sun
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: You
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007511:Ischemia / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D054086:KATP Channels / Q000378:metabolism*; D035002:Lower Extremity / Q000098:blood supply*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D013552:Swine; D013556:Swine, Miniature; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D054086:KATP Channels; D054460:rho-Associated Kinases