Role Of Inflammation In Initiation And Maintenance Of Atrial Fibrillation In Goat

Objective Atrial fibrillation(AF) is the most common sustained arrhythmia in clinical practice,and the prevalence of AF is strongly age-dependent.AF is associated with an increased mortality and morbidity from stroke and thromboembolism,heart failure and impaired quality of life.Therefore attention has been directed towards understanding the underlying pathophysiology of this condition,to provide novel insights into improving the therapeutic management of this condition.There are emerging data to support a significant association between inflammation and the development,recurrence and perpetuation of AF. For example,AF patients are always accompanied with an elevation of CRP level, and AF may be induced by the active inflammatory process.In addition,the increasing data supports a reduction in the development of AF by 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors (statins) use which provides an anti-inflammatory action.However,the causality of AF and inflammation remains controversial.This study was designed to determine the relationship between AF and inflammation in goat sterile pericarditis model and atrial tachypacing model,to analyze the role of inflammation on the atrial electrophysiological properties,and to assess the effect of atorvastatin on AF.Methods 1.Fifteen adult male goats were randomly divided into control, pericarditis,and atorvastatin groups.Atorvastatin was administered orally(60 mg/day) beginning 1 week before the operation until the end of the study in atorvastatin group.The chest was opened through the left fourth intercostal space, and pericardial electrodes patches were sutured on the left atrium(LA) and right atrium(RA).The sterile pericarditis model was established in pericarditis and atorvastatin groups.At baseline,24,48,72 hours and 7,14,21 days after the operation,atrial effective refractory period(ERP),ERP rate adaptation, conduction velocity(CV),and duration of induced AF,and hs-CRP,IL-6,TNF-αlevels were measured.2.Fifteen adult male goats were randomly divided into control,atrial tachypacing(ATP),and atorvastatin groups.Atorvastatin was administered orally(60 mg/day) beginning 1 week before ATP until the end of the study in atorvastatin group.All goats were instrumented with epicardial electrodes patches on LA and RA.Goats in ATP and atorvastatin groups were subjected to atrial tachypacing(ATP) at 400～450 bpm.At baseline,24,48,72 hours and 7, 14 days after tachypacing onset,ERP,ERP rate adaptation,CV,and duration of induced AF,and hs-CRP,IL-6,TNF-αlevels were measured.Results1.(1) Levels of hs-CRP,IL-6 and TNF-αelevated significantly after the operation in pericarditis and atorvastatin groups(p＜0.05) with a peak elevation of hs-CRP, IL-6 and TNF-αlevels at 48～72 hours after the operation,and were higher than that in control group(p＜0.05).Atorvastatin group had a lower hs-CRP,IL-6 and TNF-αlevels than pericarditis group(p＜0.05).(2) ERP and ERP rate adaptation of pericarditis goats decreased significantly after the operation(p＜0.05).Atorvastatin group had a longer ERP and a higher ERP rate adaptation than pericarditis group (p＜0.05).There was significant negative correlation between ERP and hs-CRP level in pericarditis group.(3) There was no significant change in CV in all groups after the operation.(4) The inducibility of AF in LA and duration of AF in pericarditis and atorvastatin groups increased after the operation(p＜0.05).And pericarditis group had a longer duration of AF than atorvastatin group(p＜0.05). The inducibility of AF in RA unchanged before and after the operation in all groups.2.(1) ERP of LA in ATP and atorvastatin groups decreased gradually(p＜0.05) and reached a steady state at 7 days.Atorvastatin group had a longer ERP in LA than ATP group since 48 hours after tachypacing onset(p＜0.05).There was no difference in ERP in RA between ATP and atorvastatin group.(2) ERP rate adaptation in ATP group decreased gradually(p＜0.05) and was lower than that in atorvastatin group(p＜0.05).(3) There was no significant change in left and right atrial CV in all groups.(4) Levels of hs-CRP,IL-6 and TNF-αin ATP group elevated gradually(p＜0.05) and was higher than that in control group(p＜0.05). Atorvastatin group had a lower hs-CRP,IL-6 and TNF-αlevels than ATP group (p＜0.05).(5) The inducibility of AF in LA and duration of AF in ATP and atorvastatin groups increased gradually(p＜0.05) and were all higher than that in control group(p＜0.05).The inducibility of AF in LA at 14 days in ATP group was 100%.The inducibility of AF in LA in atorvastatin group was lower than ATP group since 48 hours after tachypacing onset(p＜0.05).The inducibility of AF in RA unchanged in all groups.Atorvastatin group had a shorter AF duration than ATP group(p＜0.05).Conclusion Inflammation may promote AF by shortening atrial ERP and adaptation of ERP to rate,which might be a potential "substrate".And the elevation of hs-CRP,IL-6,TNF-αinduced by atrial tachyarrhythmia suggests that AF may induce an inflammatory process.Consequently,inflammation resulted from AF will aggravate atrial electrical remodeling further,promote "AF begets AF" together with AF,and ultimately facilitate the perpetuation of AF. Inflammation plays an important role in the initiation and maintenance of AF. Atorvastatin can attenuate AF promotion by inhibiting inflammation both in goat sterile pericarditis model and atrial tachypacing model.This indicates that atorvastatin may prevent AF post-cardiacsurgery and recurrence of AF.