Remote preconditioning, perconditioning, and postconditioning: a comparative study of their cardioprotective properties in rat models

Abstract

OBJECTIVE:Ischemia reperfusion injury is partly responsible for the high mortality associated with induced myocardial injury and the reduction in the full benefit of myocardial reperfusion. Remote ischemic preconditioning, perconditioning, and postconditioning have all been shown to be cardioprotective. However, it is still unknown which one is the most beneficial. To examine this issue, we used adult male Wistar rat ischemia reperfusion models to compare the cardioprotective effect of these three approaches applied on double-sided hind limbs.METHODS:The rats were randomly distributed to the following five groups: sham, ischemia reperfusion, remote preconditioning, remote perconditioning, and remote post-conditioning. The ischemia/reperfusion model was established by sternotomy followed by a 30-min ligation of the left coronary artery and a subsequent 3-h reperfusion. Remote conditioning was induced with three 5-min ischemia/5-min reperfusion cycles of the double-sided hind limbs using a tourniquet.RESULTS:A lower early reperfusion arrhythmia score (1.50±0.97) was found in the rats treated with remote perconditioning compared to those in the ischemia reperfusion group (2.33±0.71). Meanwhile, reduced infarct size was also observed (15.27±5.19% in remote perconditioning, 14.53±3.45% in remote preconditioning, and 19.84±5.85% in remote post-conditioning vs. 34.47±7.13% in ischemia reperfusion, p<0.05), as well as higher expression levels of the apoptosis-relevant protein Bcl-2/Bax following global (ischemia/reperfusion) injury in in vivo rat heart models (1.255±0.053 in remote perconditioning, 1.463±0.290 in remote preconditioning, and 1.461±0.541 in remote post-conditioning vs. 1.003±0.159 in ischemia reperfusion, p<0.05).CONCLUSION:Three remote conditioning strategies implemented with episodes of double-sided hind limb ischemia/reperfusion have similar therapeutic potential for cardiac ischemia/reperfusion injury, and remote perconditioning has a greater ability to prevent reperfusion arrhythmia.

Remote Ischemic Conditioning

“…However, these are empiric choices, the optimal algorithm has not been identified, and it has been postulated that “hyperconditioning” (i.e., an as-yet undefined, excessive number of conditioning episodes) may be deleterious (33,34). With regard to timing, outcomes of the limited number of head-to-head comparisons revealed no apparent difference in efficacy of RIPC, remote preconditioning, and postconditioning (35,36). The paradigms of remote ischemic perconditioning and postconditioning may be particularly relevant, as they expand the potential scope for clinical translation of RIC.…”

Effects of Renal Ischemic Postconditioning on Myocardial Ultrastructural Organization and Myocardial Expression of Bcl-2/Bax in Rabbits

“…However, based on the information currently available regarding the mechanisms of preconditioning and postconditioning [51–55], we speculate that RI-PostC resulted in the renal release of various mediators, possibly including NO and adenosine, that acted on the heart to limit the damage associated with reperfusion. The cardiac signaling mechanisms activated by these mediators likely included the PKC pathway, reperfusion injury salvage kinase (RISK) pathway (PI3K/Akt and ERK signaling with downstream inhibition of GSK-3 β ), guanylate cyclase/cGMP pathway, and JAK/STAT3 pathway [51–55]. In turn, these pathways would act to reduce cellular and mitochondrial calcium overload and inhibit necrosis and apoptosis via alterations in Bcl-2/Bax expression, opening of the mitochondrial ATP channel, and inhibition of mPTP opening.…”

Protective effect of contralateral, ipsilateral, and bilateral remote ischemic preconditioning on spinal cord ischemia reperfusion injury in rats

“…The limb RIPC may stimulate the spinal cord tissue to adjust to a future ischemic occurrence (18). In addition, the previous study shows that limb RIPC are associated with the antiapoptotic proteins such as Bcl-XL and Bcl-2, and they promote cell survival (29).…”

“…There is a hypothesis that infarct size lonely does not reflect the protective effect of a neuroprotetive material (18). Some mechanisms that describe the effect of the RIPC on the reducing the infarct size including the actions of purine nucleoside (adenosine), and mitochondrial channel closure and openness (29).…”