| Background and objectives: The normal heart structure and function ensures the integrity of myocardial cells, sequential electrical conduction and mechanical contraction, when the heart is attacked by some damages from inside or outside, it modulates itself to some extent against the injury, we call this adaptive capacity as myocardial remodeling. It is activated by the cell-cell signal transduction and leads to remodeling of myocardial cells, extracellular matrix and vascular endothelium, the research on these procedures could help clarify the development of heart disease, and then take some appropriate measures to delay or reverse the lesion. Cardiac gap junctions are the basal structure of electrical conductivity, without the ordial array and quantities of gap junctions, it will result in decreasing stability of cardiac electrophysiology and the occurrence of arrhythmias. The studies on atrial arrhythmias in recent years have shown that the size of atrial diameter, the atrial pressure, the dysfunction of endothelium, gap junction protein modification plays a vital role in the development and maintenance of atrial fibrillation(AF), what is more, in the vagus nerve-mediated atrial fibrillation(vagal AF), how the vagus nerve fibers modulate the atrial substrate metabolism, the relationship between them are still unclear. Atrial Collagen Volume Fraction(CVF) calculates the content of collagen fibers among intercellular substance and indicates atrial fibrosis. This research is based on removal or retention of cardiac vagus nerve and rapid atrial pacing animal models, to analyze the quantity of atrial Connexin(Cx)40, Cx43mRNA and their heterogeneity of spatial distribution and atrial CVF. We aim to elucidate the probable mechanism of cardiac vagal nerve which originates from the superior vena cava and aortic root fat pad(SVC-Ao fat pad), and that of atrial fibrillation inducing atrial electrical and structural remodeling.Methods: 24 mature healthy mongrel dogs are randomly divided into sham operation group(S group, n=8), SVC-Ao fat pad removal group (R group, n=8) and SVC-Ao fat pad reserved group (Re group, n=8). Anesthesia in the dogs was induced with sodium pentobarbital, (15mg/kg, peritoneal injection.) At the right third intercostal space incision, revealed the junction between the roots of aorta and superior vena cava sufficiently, where there is a fat pad called SVC-Ao fat pad, and it is the origin of vagus in heart. The difference between R group and Re group is whether excise that fat pad. R group animals were excised SVC-Ao fat pad, not but the Re group animals. Then, sutured one unipolar epicardial pacing lead (Capsure, 4965, Medtronic) to the high right atrial epicardium and the other end connected to a pulse generator (Electrical Engineering, Fudan University ) implanted in a subcutaneous pocket and programmed to pace the right atrium at 500-650 bpm with 0.2 ms pulse at two times threshold current. The pacemaker was turned off at the end of the operation and restarted after animals recovered from the wound and successively paced for 6 weeks, leaving the other eight dogs experienced sham operation and raised for 6 weeks as control. After 6 weeks, all dogs were sacrificed, left atrium(LA), right atrium(RA), left atrial appendage(LAA), right atrial appendage(RAA) and atrial septum(AS) were collected and frozen in liquid nitrogen for quantifying the expression of Cx40, Cx43mRNA by Real-time quantitative Reverse Transcription Polymerase Chain Reaction(RT-PCR) or stained with HE and Masson Trichrome.Results: (1) The incidence of atrial fibrillation: The incidence of persistent atrial fibrillation events in SVC-Ao fat pad reserved group was 5/7(71.4%), and lasted for 52.0±6.2min. (2) The expression of Cx40mRNA: The quantity of Cx40mRNA in removal group(3.89±0.73) and reserved group(4.15±0.77) was more than sham operation group(3.36±0.76, P<0.05), but there was no significant difference between these two experimental groups(P>0.05); meanwhile, in sham operation group, there was no significant difference on Cx40mRNA expression at LA, RA, RAA and AS locations, but lower than that of LAA(P<0.01); in SVC-Ao reserved group, the expression of Cx40mRNA was significantly higher at LAA and RAA(P<0.05). (3) The expression of Cx43mRNA: The expression in reserved group was significantly reduced at LA, RA, LAA and RAA while significantly increased at AS compared with sham operation group. Without the consideration of spatial distribution, the expression significantly decreased in reserved group(2.59±1.15) but increased in removal goup(5.62±2.45), which compared with sham operation group(4.32±1.87, P<0.05). (4) The Collagen Volume Fraction: Spatial distribution of collagen fibers as well as CVF between sham operation and removal groups was similar(P>0.05), CVF was significantly higher in reserved group compared with removal group, especially at LAA and AS locations(P<0.05). Conclusions: (1) The cardiac vagus nerve originated from SVC-Ao fat pad mediates the atrial electrical remodeling, which facilitates the provocation and maintenance of atrial fibrillation events, however, this effect is attenuated by denervation. (2) Rapid chronic atrial pacing can change the contents of Cx40,Cx43mRNA, their atrial spatial distribution as well, such structural heterogeneity that an important substrate for arrhythmia results in increasing the heterology of myocardial electric conduction; However, the excision of SVC-Ao fat pad, which is effective to reduce the incidence of atrial fibrillation by minimizing vagus nerve-induced atrial electrical remodeling. (3) There is obvious collagen deposition in atrial interstitial substance, which is accompany with myocardial hypertrophy, fragmentation and inflammatory infiltration, cardiac vagus nerve can modulate the fibrous tissue metabolism at different locations of atrium, removal of SVC-Ao fat pad attenuates atrial heterogeneity of structural remodeling after rapid pacing. |
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