Experimental Study On Relationship Between Ageing And Atrial Fibrillation

Objective To investigate the ageing-related changes of electrophysiological properties of atria, pulmonary vein(PV), and vena cava(VC) in healthy canine; to evaluate the effects of aging on tissue remodeling of atria and veins and, on gap-junction protein of atrial myocardium and mycardial sleeves and also on cell microstructure in atria and PVs. Based on above studies, the potential relationship between the ageing-related changes of atria and veins and the onset of AF was to be determined.Methods Fifteen healthy mongrel dogs(weight 14.3 to 24.2kg, ranged from 0.75 to 10 years) were divided in to three groups: young, adult, and elderly dogs.1. Multielectrode catheters, for local electrical stimulation and electrogram recording were transvenously or transseptally introduced into the hearts and positioned at PVs, atria, and vena cavas(VC) respectively. The parameters at different places of atria and the veins which included in ERP, CV, WL, vulnerability of atria, adaptability, and conduction delay were measured and compared. Correlations between the parameters and age were analyzed.2. At the end of the electrophysiological study, chests of the dogs were opened and the atria with PVs and VCs were cut off along the atrioventricular ring. Diameter of PVs, length and thickness of myocardial sleeves were measured respectively. The sections were stained with either hematoxylin and eosin stains or with picrosirius-red. Relative contents of myocardial collagen(type of I andIII) were calculated by pathological image analysis system, and the type of I and III collagen would be compared with each other. The slides through immunofluorescence histochemistry processes were examined by confocal microscopy, and areas of the fluorescent light spots which represented Cx40 and Cx43 were calculated and analyzed by image analysis system. Electron microscopy Small tissue samples (1mm3) from the free wall of atria and the tip of myocardial sleeves of PVs were cut off and fixed, and ultrastructures were visualized using a transmission electron microscope.Results1 .Electrophysiological properties The duration of the P wave in elderlycanine was significantly longer than in the others, P<0.05. Left atrial ERP showed a aging-related increase, especially at old age, P<0.01, but the PV-ERP prolonging occurred only at old age, P=0.01. Both left atrial ERP and PV-ERP presented significant correlation with aging, and the r of LA-ERP was 0.79, PO.001, r of PV-ERP =0.735, P=0.001. In old dogs, CV was slower than in young, and a negative correlation lived in atria and aging, P<0.001. In PVs, activity conducting longitudinally was more faster than conducting transversally, P<0.05. However, CV in veins did not show correlation to aging, but the value of difference between transversal CV and longitudinal CV had a positive correlation with aging in PV, r=0.65, P=0.004. In old dogs, conduction delay in PVs developed frequently after premature stimulating, P<0.001, and the frequency adaptation was not as good as of RA, so as to PV compared with SVC, P<0.01. AF load presented a trend of increase as aging advanced.2. Anatomical-histologic analyses and Electron microscopy Of all the 15 dogs, the gross anatomy had no significant difference, there were 58 PVs measured in this study. Myocardial sleeves were seen in 94.83% PVs and 86.67% PVs presented 4 main branches. The thickness and extension of myocardial sleeves of superior PV and mean diameter of ostium of PV were more than inferior PV(P<0.05). Histology revealed a significant aging-related significant increase in interstitial atrial fibrosis (Type of I collagen) of both atria and PVs, P<0.05, or 0.001, however, the aging-related increase in type of Illcollagen was not so much .In contrast, aging-related increase of the ratio of I /III collagen showed only in LA, P< 0.05, not in PV. Both Cx40 and Cx43 were presented throughout the atrial and myocardial sleeve myocytes, but Cx43 was predominantly presented at myocytes and, Cx40 was scarcely seen at myocytes of PVs. A aging-related decrease of Cx43 expression was seen in atria and PVs, PO.01. The aging-related changes of ultrastructure were mainly focused on the presentations of mitochondria distortion, prolonging, and multiplying, and intercalated disc remodeling, as well as small fiber hyperplasia in PVs.Conclusion1 .Aging significantly prolongates ERP of atria and raise the dispersion of ERP, then promotes degradation of frequency adaptation of atria and PVs. CV in...