Combined postconditioning with ischemia and α7nAChR agonist produces an enhanced protection against rat myocardial ischemia reperfusion injury

Background Inflammation is one of important mechanisms for myocardial ischemia reperfusion injury （IRI）.Ischemia postconditioning （IPOC） can protect the heart against IRI by inhibiting inflammation,but its cardioprotection is weaker than that of ischemia preconditioning.Recently,the α7 subunit-containing nicotinic acetylcholine receptor （α7nAChR） agonist has shown anti-infiammatory effects in many diseases related to inflammation.This randomized controlled experiment was designed to evaluate whether combined postconditioning with IPOC and the α7nAChR agonist could produce an enhanced cardioprotection in a rat in vivo model of acute myocardial IRI.Methods Fifty Sprague-Dawley rats were randomly divided into five equal groups：sham group,control group,IPOC group,α7nAChR agonist postconditioning group （APOC group） and combined postconditioning with IPOC and α7nAChR agonist group （combined group）.Hemodynamic parameters were recorded during the periods of ischemia and reperfusion.Serum concentrations of troponin I （Tnl）,tumor necrosis factor α （TNF-α） and high-mobility group box 1 （HMGB-1） at 180 minutes after reperfusion were assayed in all groups.At the end of the experiment,the infarct size was assessed from excised hearts by Evans blue and triphenyl tetrazolium chloride staining.Results As compared to the sham group,the infarct size in the other four groups was significantly increased,serum levels of Tnl,TNF-α and HMGB1 in the control group and TNF-α,HMGB1 in the IPOC group were significantly increased.The infarct size and serum concentrations of TNF-α,HMGB1 and Tnl in the IPOC,APOC and combined groups were significantly lower than those in the control group.As compared to the IPOC group,the infarct size in the combined group was significantly decreased,serum concentrations of Tnl,TNF-α and HMGB1 in the APOC and combined groups were significantly reduced.Although the infarct size was significantly smaller in the combined group than in the APOC group,serum levels of TNF-α and HMGB1 were significantly higher in the combined group than in the APOC group.Conclusions In a rat in vivo model of acute myocardial IRI,combined postconditioning with IPOC and the α7nAChR agonist can produce enhanced protection against myocardial IRI by increasing the anti-inflammatory effect.

Remote ischemia conditioning-an endogenous cardioprotective strategy from outside the heart

Objective A general review was made of studies involving： （1） The experimental evidence of remote ischemic preconditioning （RIPC） and relative clinical studies, （2） The experimental and clinical evidences of remote ischemic postconditioning （RIPOC）, （3） The potential mechanistic pathways underlying their protective effects.Data sources The data used in this review were mainly from manuscripts listed in PubMed that were published in English from 1986 to 2010. The search terms were ＂myocardial ischemia reperfusion injury＂, ＂ischemia preconditioning＂,＂ischemia postconditioning＂, ＂remote preconditioning＂ and ＂remote postconditioning＂.Study selection （1） Clinical and experimental evidence that both RIPC and RIPOC produce preservation of ischemia reperfusion injury （IRI） of myocardium and other organs, （2） Studies related to the potential mechanisms, by which remote ischemic conditioning protects myocardium against IRI.Results Both RIPC and RIOPC have been shown to attenuate myocardial IRI in laboratory animals. Also, their cardioprotective effects have appeared in some clinical studies. Except the external, the detailed internal mechanisms of remote ischemic conditioning have been generally described. Through these descriptions better protocols can be developed to provide improved cardioprotective procedures.Conclusions Remote ischemic conditioning is an endogenous cardioprotective mechanism from outside the heart that protects against myocardial IRI and represents a general form of inter-organ protection. Remote ischemic conditioning may have an immense impact on clinical practice in the near future.