CardiothoracicProtection “Outside the Box” (Skeletal Remote Preconditioning) in Rat Model is Triggered by Free Radical Pathway
Introduction
Ischemic preconditioning (IPC) has been explored widely in various experimental models since 1986 [1], and it also has been observed in organs other than heart [2, 3, 4]. The concept of intraorgan “remote preconditioning” (RPC) has been advocated previously in that a brief period of ischemia in one region of the heart was able to reduce the infarct size of the different part of myocardium [5]. Liauw et al. [6] also demonstrated that RPC of one skeletal muscle could be practiced to protect the contralateral muscle from an ischemia-reperfusion (I/R) injury.
The concept of intraorgan RPC was extended to the interorgan RPC by Gho et al. [7]. Interorgan RPC protects against myocardial infarction through various mechanisms, such as adenosine and the central nervous system [7, 8]. Skeletal RPC, by rapid stimulation of the muscle combined with partial reduction of blood supply, also has been shown to elicit a protective effect by a reduction of infarct size [9]. Skeletal RPC appears to be a good way for myocardial protection, but some controversial data still exist [10, 11, 12]. Only muscle stimulation and reduced blood supply have a protective effect, and no further investigation concerning the proposed mechanism has been undertaken [9]. A human study in vivo in coronary artery bypass with cardiopulmonary bypass did not show a conclusive result in skeletal RPC [10]. A short period of limb ischemia could have an antiarrhythmic effect in isolated rat heart, which might be mediated through the norepinephrine receptor [12]. There was few in vivo data concerning the skeletal RPC, and no trigger mechanism concerning skeletal RPC has been studied.
We tested the hypothesis that short periods of limb I/R can induce RPC and reduce the infarct size in acute infarction model and that free radicals might be involved in the skeletal RPC and act as triggers. The expression of heat-shock protein (HSP) and the antioxidant enzymes were evaluated.
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Materials and methods
Wistar rats, weighting 200–300 g were used for this study. All animal experiments and care were performed in accordance with the “Guide for the Care and Use of Laboratory Animals” (published by National Academy Press, 1996). The Laboratory Animal Care Committee of our institution approved all protocols in this study.
Preliminary Result of Free Radicals Detected by CL
The results of free radicals in different groups with/without MPG infusion were shown in Fig. 2A for groups I to IV and Fig. 2B for groups with MPG (n = 9 for each groups). The CL count was not elevated in group I and III at all time points except for point C (P < 0.05, compared with point A and A′; Fig. 2A), which might be attributed to the prolonged experiment. The free radicals in group II and IV were not significantly elevated immediately after RPC (point A′ versus point A) but were
Discussion
This study proves that skeletal RPC can have the protective effect for subsequent myocardial infarction by reduction of the infarct size and the release of cardiac enzymes and that the skeletal RPC protective effect may be triggered by the free radicals, which can be abrogated by the free radical scavenger, MPG. We also highlight RPC-related cardioprotection in the in vivo model.
A prolonged coronary occlusion model (ranging from 90 min to 2 h) was applied to delineate the intraorgan
Conclusion
The application of the skeletal RPC technique using a four-cycle 10-min I/R model before an elicited myocardial infarction could result in reduction of the elicited infarct size and also a reduction in the level of myocardial enzyme release. The protective effect seems to be triggered by free radicals. HSP and antioxidant enzymes were associated partially involved in the RPC process.
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