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Colchicine Reduces Incidence Of Atrial Arrhythmias In Rabbit Sterile Pericarditis Models Through Anti-inflammatory And Reducing Expression Of Kir3.4mRNA.

Posted on:2014-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:X ChenFull Text:PDF
GTID:2234330398477613Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
BackgroundThere is a high incidence of atrial fibrillation (AF) after cardiac surgery, for instance,the incidence of AF is about30percents after Cardiac Artery Bypass Grafting(CABG) and almost up to64percents after Rheumatic heart valve replacement. Its complications such as stroke, peripheral vascular embolization, heart failure brought about the high morbidity and high fatality rate,and then greatly damage the patient’s quality of life, increase the family and social medical burden.The occurrence of AF after heart surgery is considered to be related to local or systemic inflammatory reaction after cardiac surgery for quite a long time.The latest research suggests that colchicine can safely and effectively used in the treatment and prevention of acute pericarditis and recurrent pericarditis. Current research has shown that,after heart surgery, lymphocytes or mononuclear cells infiltration could be found by interatrial septum endocardium biopsy.The occurrence of AF after heart surgery is associated with persistent inflammation reaction.As an anti-inflammatory drug, Colchicine, has been used in the treatment of pericarditis for a long time. In2011AHA2011science conference, colchicine was highlighted because in COPPS research subgroups it reduced the risk of AF incidence nearly half, and shortened hospital stay.AF incidence in dog sterile pericarditis atrial fibrillation models is quite high both at home and abroad,and the changes of pathophysiological and acute reaction period protein (CRP) in these models is the same as these of patients after heart surgery.At present, study suggested the use of colchicine can reduce postoperative recurrence of atrial fibrillation after radio AF frequency ablation.But there are rarely related reports on the mechanisms and the targets of how colchicine reduce AF incidence or recurrence after cardiac surgery or AF radio frequency ablation. So we can stay the changes of local atrial inflammatory reaction electrical remodeling in rabbits through the establishment of rabbit sterile pericarditis atrial fibrillation models, and then we explore their relationships with the incidence of AF. Then we may understand the mechanisms and the targets of how colchicine reduce AF incidence or recurrence after cardiac surgery or AF radio frequency ablation and its effects on electrical remodeling and structural remodeling. The study may do some new and beneficial explorations to the prevention and treatment of AF after cardiac surgery or AF radiofrequency ablation.Objective:To observe how colchicine influences the incidence of atrial arrhythmias in the rabbit sterile pericarditis models,and to explore its possible mechanisms.Methods:Sterile talcum powder was perfused on the left and right atrium surfaces of the rabbit in order to establish sterile pericarditis model, the pacemaker electrode was then seamed in the left atrium surface.So the pacemaker could be implanted under the abdominal subcutaneous tissue,which was used to provide high frequency short time stimulation. The36healthy adult male rabbits were randomly divided into three groups, control group, pericarditis group and colchicine group,12of each group.All of the rabbits in the three groups were undergoing thracotomy in the left sternum margin between the Second and third intercostals.Suspending the pericardium, then cutted it off. A pacemaker electrode was seamed in the surface of each rabbit’s left autium,then the pacemaker electrode went across the subcutaneous tissue of the abdomen where a pacemaker capsule bag was made.The left and right autriums of both the pericarditis group and colchicine group were perfused by1to2grams of sterile talcum powder, but the control group not. All of the rabbits were given high frequency short time stimulations (Stimulus frequency was640times per minute, stimulation time was60seconds)on the first,second,third and fifth day after operation.At the same time the body surface electrocardiograms and the duration of atrial arrhythmias were recorded, and the rates of atrial arrhythmias of each group were calculated.On the fifth postoperative day,when all the observations were done, all the rabbit would be killed respectively by group. One part of the right autriums of the rabbits would be dyed by HE to see if there were any inflammatory cells among the atrial muscle tissues.While the last parts were used to do fluorescence quantitative PCR detections to test the expression levels of atrial muscle cell KAch channel kir3.4mRNA.Statistical methods:(x±s) was adopted in measurement data., one-way ANOVA,t test or Wilcoxon rank test were used in comparisons among groups. Fisher’s exact test is used for the test of incidence and positive rate. P<0.05for significant differences.Results:1. Compared with control group, fast arrhythmia incidence increased significantly (P<0.01) in pericarditis group; Compared with pericarditis group, fast atrial arrhythmia incidence was decreased by45.4%(P<0.01), inflammatory cells infiltration rate decreased54.5%(P<0.05) in colchicine group5days after surgery.2. Compared with control group, the lasting time of fast atrial arrhythmia increased significantly (P<0.01) in pericarditis group; Compared with pericarditis group,,the lasting time of fast atrial arrhythmia was significantly decreased in colchicine group5days after surgery (.P<0.05)3. Five days after surgery,inflammatory cells infiltration was found in9cases (82%) in pericarditis group, which was significantly higher than control group (1case (10%), P<0.01) analysed by FISHER’s exact test; inflammatory cells infiltration was found in3cases (27%) in colchicine group, which was significantly reduced compared with the pericarditis group (P<0.05).4. Compared with Group B, the kir3.4mRNA expression level of Group significantly reduced (P<0.05). Conclusion:Colchicine can reduce the incidence of atrial arrhythmias in the rabbit sterile pericarditis model. The possible mechanism may be colchicine can alleviate atrial muscle tissue inflammation reaction and reduce the expression of Kach channel kir3.4mRNA.
Keywords/Search Tags:Atrial fibrillation, Sterile pericarditis, Potassium channel, Colchicine
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