The Time-dependent Study On Connective Tissue Growth Factor And Nerve Remodeling In Atrial Fibrillation

Objective: To dynamically observe the mechanism of connective tissue growthfactor and nerve remodeling in the atrial fibrillation rabbit models. Methods:1)Ninety-six rabbits were randomly divided into2groups: control group (n＝48) were notpaced, AF group (n＝48) underwent rapid atrial pacing, and each group were divided into6subgroups,4h group,8h group,12h group,16h group,20h group and24h group (n＝8,respectively). The changes of AF inducibility, effective refractory period (ERP), dispersionof ERP, rate-adaptation of AERP and heart rate variability (HRV)were examined beforepacing and after pacing.2) Left and right atrial diameter and left ven-tricular ejectionfraction (EF) were examined by cardiac ultrasonography. Plasma concentration of CTGFwas detected by enzyme-linked immunosorbent assay.3) The changes of CTGF and nervegrowth factor(GAP-43, ChAT, TH) was detected by immunohistochemistry. Results:1)After pacing8h, atrial fibrillation inducibility was significantly increased, duration of AFwas significantly prolonged, AERP was significantly shortened, dispersion of AERP wassignificantly decreased and the rate-adaptation of AERP was significantly increased.2)The left and right atrial volume were enlarged with the pacing prolonging, but there wasno significance(P＞0.05). The EF at pacing12h was significantly decreased (P＜0.05).3)The plasma and tissue CTGF levels at pacing16h were significantly progressivelyincreased (P＜0.05).4) HRV frequency domain, the LF and HF at pacing8h and12h weresignificantly increased (P＜0.05), the increading of LF and HF reached a peak at16h andgradually discreased later. In AF group, the LF/HF was increased to the highest values (P＞0.05) at4h, and then decreased to the lowest values(P＞0.05).5) GAP-43, TH andChAT positive nerve density in left and right atria were significantly increased atpacing12h (P＜0.05) and then gradually increased. However, the TH-positive nervedensity in right atrium was higher than the left atrium, but the difference was not significant (P＞0.05). Conclusion:1) Atrial electrical remodeling occurred after rapidatrial pacing8hours.2) Cardiac function decreased, atrial structure changed after rapidatrial pacing8hours.3) CTGF increased after rapid atrial pacing16hours,whichindicating myocardial fibrosis.4) Neural remodeling occurred after rapid atrial pacing16hours, and vagal nerve tone was dominant.5) The changes of CTGF and HRV wereconsistent, which may be used to predict the myocardial fibrosis development of atrialfibrillation.