Protection “Outside the Box” (Skeletal Remote Preconditioning) in Rat Model is Triggered by Free Radical Pathway

Abstract

Remote preconditioning (RPC) for myocardial protection had been demonstrated in several organs, such as the kidney and mesentery artery. The aim of study was to investigate the effect of skeletal ischemia/reperfusion on coronary artery occlusion-induced myocardial infarction and to investigate the role of the free radicals. RPC was performed in rats by a repeated four-cycle 10-min ischemia-reperfusion of femoral artery. Four experimental groups were included: I, sham group; II, RPC only; III, infarction only; and IV, which incorporated both RPC and infarction. A chemiluminescence study showed significant elevation of free radicals in groups with RPC, and pretreated mercaptopropionyl-glycine (MPG), a free radical scavenger, abolished the production of free radicals. The infarct size was significantly reduced for group IV (24.7 +/- 8.8%) compared with group III (51.4 +/- 9.1%; P < 0.001), and the effect was abolished by pretreatment with MPG (49.2 +/- 6.3% in MPG + III versus 50.1 +/- 8.2% in MPG + IV; P > 0.05). Cardiac enzymes also revealed significant decrease in the level for group IV compared with group III, and the protective effect could be abolished by MPG. Western blotting of heat shock protein (HSP) revealed that consistent elevation of HSP 25 and 70 in groups II, III, and IV, and the elevation can be abrogated by pretreatment with MPG. The expression of the antioxidant enzymes, Mn-superoxidase dismutase and glutathione peroxidase, in the area of risk were consistently elevated in groups II, III, and IV, similar to HSP. The skeletal RPC in rats can produce a protective effect in an infarction model that may be triggered through free radical pathway, and the protective effect was associated with HSP and antioxidant enzymes.