Empirical Study Of Time Dependence Nerve Remodeling In A Canine Model Of Atrial Fibrillation Produced By Pacing 48 Hours Right Atrial

Objectives: To investigate the effect of 48 hours atrial fibrillation induced by high right atrium pacing on remodeling of atrial nerve,structure and electrical as well as on the function of left ventricular in canine. Methods: Establishing atrial fibrillation model induced by a rapid right atrial pacing (600 beats/min), left ,right atrium size and left ventricular ejection fraction were measured and atrial effective refractory period(AERP) after AF 0,6,12,18,24,30,36,42,48 hours respectively, echocardiogram and the changes of atrial architectonic ; Immunocytochemical staining of cardiac nerves was performed using anti– growth-associated protein 43 (GAP43) and anti–choline acetyltransferase (CHAT) and anti–tyrosine hydroxylase (TH) antibodies.To comprehend nerve sprouting and nerve remodeling by these indexes;After 48 hours,single myocytes were isolated by Langendorff perfusion apparatus and enzymatic dissociation. The current of L-type calcium channel was recorded by patch clamp technique in the whole cell mode. Results:1.With the time continue,left,right atrium transverse diameter gradually increased, but have no significant difference (P>0.05).Left ventricular function significantly decreased 21.4%,22.8%,25.5% and 31.4% on AF 12 hour,24 hour,36 hour and 8 hour compared with that AF 0 hour.( P<0.05).2. It can be seen that atrial muscle cells endocytoplasmic reticulum is broaden, bioblast is engorge and deposit of glycogen in electronmicroscope; HE stain in right atrium tissue of AF suggest that atrial muscle cells disarray and compartment of atrial muscle cells are widen; Right atrium tissue of control group are structural integrity and arraial regularity. Masson stain in AF and control group can see a small quantity deposit of collagen fibers and deposit of glycogen.3. In dogs with AF,the density of GAP43-positive,CHAT-positive and TH-positive nerves in the left and right atrium and left and right auricular appendage which was significantly (P<0.05) higher than the nerve density in control tissues; Furthermore, in dogs with AF, the right atrium had significantly higher nerve density of GAP43-positive and CHAT-positive than the left atrium(P<0.05). Microscopic examinations revealed an inhomogeneous distribution of cardiac,but the left,right atrium and left,right auricular appendage had no significantly higher nerve density of TH-positive .4.After 48 hours atrial fibrillation,ICa-L peak current density of AF group was significantly reduced in different clamp voltage, peak current density was -3.7±0.50PA/PF(n=15),the density of ICa-L current was significantly decreased than control group-5.74±0.20PA/PF(n=13) (P < 0.05). Conclusion: 1. 48 hours AF induced by a rapid right atrial pacing (600 beats/min)can cause electrical and functional remodeling; 2. Ultramicrostructure and histologically of right atrium have changes in 48 hours AF group; 3. Significant nerve sprouting and nerve remodeling are higher in the right atrium than in the left atrium in a canine model of sustained AF produced by 48 hours right atrial pacing; 4. The density of ICa-L current is significantly decreased in 48 hours AF group.