The Delayed Protect Effect Of ACEI Pretreatment On Ischemic Reperfusion Heart

The prevention and cure of ischemic/reperfusion injury has been become predominant topic in cardiovascular research domain.Ischemic preconditioning (IP)is the strongest protective mechanism and complicate cell defence phenomena in vivo.IP existence in not only organ level but also cell level.IP can ptrtect cardiomyocytes ,vascular smooth muscle cells or endothelial cells.The detect of IP established a new domain for protect ischemic myocardium and visit its mechanism.Previous research have been illustrated that hypoxia preconditioning and is chemic preconditioning had similar effects.The cardioprotective effect of IP was subsequently found to be a biphasic phenomenon, with an early phase of protection that develops within minutes from the initial ischemic insult and a late (or delayed) phase that becomes apparent 12 to 24 hours later. Because of this, and because of its sustained duration, considerable interest has recently focused on the late phase and on its clinical relevance. If the mechanism of this adaptive metamorphosis is elucidated, then it should be possible to exploit it to protect the ischemic myocardium in patients. Presenrly to practice injury preconditioning has been not accepted in clinic for it can produce damage.Now the research of induce preconditioning has transferred from ischemic,biologic,physics and chemistry to pharmalogical.Pharmalogical preconditioning bring about cardioprotective effect for excitaed or mimic endogenous materials.Angiotensin converting enzyme inhibitor (ACEI)can produce pharmalogic preconditioning effect.It have been widely reported that ACEI induce or reinforce early cardioprotective effect,and few reported induce delay cardioprotective effect. Being a new type ACEI,fosinopril have widely clinic application and investigate value for act power,last longer,preclude bi-pathway and malresponse lightly.Up to date fosinopril late preconditioning protective effect is not reported.At present the reports are found in neither effect and mechanism of calcium transfer , L type calcium channel and sodium calcium exchanger in ACEI late preconditioning nor ACEI delay protective effect in endothial cell ischemic reperfusion(hypoxia/reoxygention) injury.For detect the upper topic,we created the ischemic reperfusion injury model for myocardial cells and endothial cells.Captopril and fosinopril were applicated to experiment.Our research should provid experiment foundation and themry background for its contra ischemic/reperfusion injury.Ⅰ。Delay protective effect of ACEI preconditioning on ischemic reperfusion myocardial cellsOur previous research showed that fosinopril had delay cardioprotective effects and alleviate ischemic reperfusion injury. The cardioprotective effects manifest (1) relieve ischemic reperfusion myocardial cells nrcrosis and apoptosis,myocardial stunning,arrhythmia.(2)ameliorate ischemic reperfusion myocardial cells electrophysiological parameter abnormal changes,attenuate conductive propert among ischemic myocardial cells,relieve repolarization disorder between normal and ischemic myocardial cells,these electrophysiological mechanism maybe decrease arrhythmia.Our next experiment intend to illustrate the effect of calcium reansfer,L type calcium channel ,sodium calcium exchanger exist in ischenix reperfusion injury and ACEI late preconditioning.1. Influence of captopril late preconditioning on hypoxia/reoxygention myocardial cells [Ca2+]i Using neonatal rat to establish culture ventricular myocytes ischemic reperfusion model, FLUO-3 is adopted to fluorescent probe, we study the effect of captopril late preconditiong on myocytes [Ca2+]i on single cell level by flow cytometry technique.The result showed as follow:(1)under normal oxygen condition, myocytes [Ca2+]I is significant difference with hypoxia(414.08±37.40 vs 789.42±9.05, P<0.05),this means calcium overload exist in hypoxia/reoxygention myocytes.(2)myocytes [Ca2+]I of hypoxia preconditioning and captopril preconditioning are significant difference with hypoxia/reoxygention...