| Background:Acute myocardial infarction is a serious threat to human health.Reperfusion therapy is the most important therapy for saving the dying myocardial cells and improving the prognosis,while reperfusion injury and reperfusion arrhythmia accompanied with reperfusion itself will make a discount.So it is necessary to control the reperfusion injury and reperfusion arrhythmia and to make more benefits.Atrovastatin has more beneficial effects beyond cholesterol reduction.There are more evidences to support that statins has anti-arrhythmic effects and can improve clinical outcomes.Gap Junction protein Connexin43 determines the electrical conducting speeds and it has an intimate relationship with reperfusion arrhythmia.Whether Atrovastatin postconditioning in ischemia/reperfusion can affect the Cx43 expression and distribution and then affect the cardiac electrical parameters and reperfusion ventricular arrhythmia is still unclear.Objectives:To observe 1.The short-time effects on QRS duration and inhibitory effect on ventricular reperfusion arrhythmia of atrovastatin in acute anterior STEMI patients after primary percutaneous coronary intervention;2.The effects of atrovastatin on ischemia/reperfusion ventricular myocardial QRS duration,LVEDP,LVDP and reperfusion ventricular arrhythmia.3.The effects of atrovastatin on expression and distribution of ischemia/reperfusion ventricular myocardial Cx43;4.The effect of the core protein of RISK signal pathway PI3K and mitochondrial-dependent potassium channel(KATP)in atrovastatin postconditioning.Methods:1.Acute anterior myocardial infarction?STEMI?patients undergoing primary percutaneous coronary intervention were randomly given routine dose atrovastatin and high dose atrovastatin.ECG and continous electrocardiogrphic monitoring were taken to observe the short-time effects on QRS duration and inhibitory effect on ventricular reperfusion arrhythmia of atrovastatin in acute anterior STEMI patients after primary percutaneous coronary intervention;2.Isolated rat ischemia/reperfusion models with Langendorff perfusion system and ligation of the coronary arteries were made.Isolated heart with multi-channel physiological instrument electrocardiographic monitor and pressure monitor were connected to record the ECG,LVEDP,LVDP and ventricular arrhythmia.The rats were divided into 8 groups by different interventions at the onset of reperfusion stage,Control group,ischemic postconditiong group,atrovastatin postconditioning group,atrovastatin with LY-294002 group,LY-294002 group,atrovastatin with 5-HD group,5-HD group and alcohol group.Effects of such interventions on the QRS duration,LVEDP,LVDP and ventricular arrhythmia score were evaluated.3.Gene expression of Cx43 with RT-PCR,expression of Cx43,P-Cx43,P-AKT with western blot and immunohistochemistry were measured.4.PI3K inhibitor LY-294002 and KATP channel inhibitor 5-HD were added to evaluate the mechanism of atrovastatin on the expression and distribution of Cx43.Results:1.In all the patients with acute anterior STEMI,QRS durations were decreased compared to it at administrarion in the two groups?p<0.01?.Shortening of ORS duration was more evident in the high atrovastatin dose group than in the routine dose group?11.09±2.19 vs 9.8±2.6,p<0.01?.Both the score of ventricular arrhythmia durning operation and 24hours after primary PCI were lower in high atrovastatin dose group than in the routine dose group.1?0,2?,2?1,2?to 1?0,2?,2?1,3?,?p<0.01?.2.Compared to ischemia/reperfusion group,atrovastatin had the same effect with ischemic postconditioning on the shortening of QRS duration,decrease of LVEDP and increase of LVDP in the early reperfusion stage;3.Atrovastatin and ischemic postconditioning had the same effect on increasing the gene and protein expression of Cx43,Atrovastatin could also influence the distribution of Cx43 and made it more regular.4.When PI3K inhibitor LY-294002 and KATP channel inhibitor 5-HD were added into the perfusate at the onset of reperfusion stage,such effects of atrovastatin on the expression and distribution of Cx43 were disappered.Conclusions:1.The present study showed that intensive dose of atrovastatin?80mg?in patients with STEMI undergoing primary angioplasty has more intensive effect in shorting the QRS duration and antiarrhythmic effect than routine dose of atrovastatin?20mg?group.2.The QRS duration of isolated rat hearts get longer in ischemic period,and then it can get shorter in reperfusion period.Atrovastatin has the same effect with ischemic postconditioning on the shorten of QRS duration,decrease of LVEDP and increase of LVDP in the reperfusion stage;Atrovastatin has the same effect with ischemic postconditioning on inhibition of reperfusion ventricular arrhythmia.The effects of atrovastatin can be attributed to the activation of PI3K/AKT and mitochondril ATP dependent potassium channel(KATP).3.Atrovastatin and ischemic postconditioning has the same effect to increase the gene and protein expression of Cx43 and P-Cx43.Electrical remodeling can be improved by atrovastatin.4.Both RISK signaling pathway and mitochondrial KATP are the key link in the atrovastatin postconditioning on Cx43 and electrical remolding. |
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