Received November 15, 2007
Revised December 14, 2007
Accepted after revision March 19, 2008
Cardiovascular Control [210]
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Brief femoral artery ischaemia provides protection against myocardial ischaemia / reperfusion injury in rats: the possible mechanisms
Mohd Shahid 1,
Mohammad Tauseef 2,
Krishna K Sharma 3,
Mohammad Fahim 3*
1 Tulane University Health Sciences Centre
2 University of Illinois at Chicago
3 University of Delhi
* To whom correspondence should be addressed. E-mail: vpciphysiology{at}yahoo.com.
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Abstract |
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Brief femoral artery ischaemia provides protection against myocardial ischaemia / reperfusion injury in rats: the possible mechanisms
Present study was conducted to examine the role of nitric oxide (NO), mitochondrial ATP sensitive K+ channels (mitoK+ATP channels) and reactive oxygen species (ROS) and their interdependence in the brief femoral artery ischaemia-induced myocardial preconditioning. To assess myocardial injury, myocardial infarction was induced by LAD coronary artery occlusion/reperfusion in anaesthetized rats and was assessed by TTC staining. Left ventricular function was assessed by LVEDP and LV(dP/dt)max. Serum CK-MB and LDH were determined by colourimetric kits. Remote preconditioning (RPC) was induced by 15 min occlusion of femoral arteries followed by 10 min of reperfusion just before LAD occlusion. Brief femoral artery ischaemia produced 61 %, 57 % & 72 % reduction in myocardial infarct size, elevated serum LDH and CK-MB activity respectively and also significant improvement in LVEDP and LV(dP/dt)max as compared to control. Pretreatment with 5-hydroxydecanoate (5-HD) or L-NAME or N-acetylcystein (NAC) blocked this protective effect of femoral artery ischaemia, independently. Moreover, L-arginine or diazoxide infusion before coronary artery occlusion markedly reduced the myocardial infarction and improved the left ventricular function. This effect of L-arginine was found to be abolished by the blockade of mitoK+ATP channels with 5-HD, and similarly, the effect of diazoxide was blocked in the presence of a ROS scavenger, NAC. The results suggest that brief femoral artery ischaemia-induced RPC is mediated by increased NO synthesis, opening of mitoK+ATP channels and increased ROS production altogether. Moreover, it appears that NO is working upstream and acts via activation of mitoK+ATP channels which subsequently increases the production of ROS in this effect.
Key Words:
Cardiovascular, Heart, Ischaemia
