The Mechanism Of Atrial Fibrillation On Sympathetic Nerves System

Atrial fibrillation (AF) is the most common arrythmia found in clinical treatment and is one of the most important reason for heart failure and stroke. Many cardiac electro physiologists focus on it in China and internationally. The therapy of AF includes two parts: medication and operation. However, both of these treatments are not the best ways since both result in some syndromes and high recrudescence. Therefore, the treatment and prevention of AF is a great challenge in the cardiac clinical field.The mechanism of AF is complex. Some studies of AF model in basic state have found re-entering, triggering and remodeling mechanisms taking place. These different mechanisms of AF occur in different kinds of diseases. The remodeling mechanism includes constructional remodeling, ionic remodeling, functional remodeling and nerve remodeling. Early clinical studies found constructional remodeling to be an important factor of AF leading to enlargement and increased pressure of the atrium. The ionic remodeling is an electro-physiological characteristic that shorten (AERP), slow conduction and repolarization heterogeneity, which lead to instability of APD. The study showed Ito, Ica, L and INa decreased in AF.Recently, scientists found that the autonomic nerve system affect AF triggering and maintaining. The autonomic nerve system releases hormones to the receptors through ionic channeling and thus affect the cardiac electrical activity. Through triggering, re-entering mechanisms and high myocardial excitement, AF would occur.Recently, people have recognized the importance of remodeling mechanism in the occurrence and progression of AF. To study remodeling mechanism in molecular level is not only to unveil the mechanism of AF occurrence, maintaining and evolvement but also help us to understand how and what medicine to use and to enable us to select the best method to treat AF. It may also give us theoretical basis of understanding of AF medication and surgery.To sum up, presently these studies do not have the last word on results and methods because of the lack of explanations on abnormal phenomena. This study sets up an animal model of AF and investigates a series of research in the effect of sympathetic nerve on the moleculear level and macrocosmic level. This study would show how the sympathetic nerve system contribute to AF.Abstract 1 Effects of Autonomic Nerves System on Paroxysmal Atrial Fibrillation Originating from the Pulmonary VeinObjective: The recent study of Atrial Fibrillation(AF) mechanism is one of the focus within the study of arrythmia. Most of the clinic and basic study discovered different AF mechanism, and approximately 90% of the AF triggered from the pulmonary vein. Right now in China and internationally much research has been done on vagal effect on AF trigger and continuing AF. On the other hand, there has been relatively little research on sympathetic nerve effect. Therefore, my research was on the application of sympathetic nerve stimulator and blockage, using quick acting atrial and LPSV to detect the mechanism of AF by the influence of sympathetic nerve.Method: 13 dogs to be compared by itself, each dog to be experimented 3 times to determine the beginning conditions of ERP in atrial, LSPV in (DMP), and the inducibility of AF and AFCL. Secondly, inject Iso to stimulate sympathetic nerve, then third, to inject Metrolol to block it. Each time check ERP, LSPV and the inducibility and AFCL.Results: 1) After different drugs intervention, atrial and pulmonary effective refractory period(ERP), ERP dispersion and coefficient of variation of ERP :After intravenous Iso, ERP of LA, HRA, LSPV-P, LSPV-M and LSPV-D are shorter than ERP of under the baseline state. After intravenous metoprolol, ERP of LA, HRA, LSPV-P are longer than ERP of under the baseline state, while there are no significant different in ERP of LSPV-M and LSPV-D. Under the baseline state, atrial and pulmonary ERP dispersion (20.1±11.2) ms; After intravenous Iso, ERP dispersion (32.2±10. 2)ms is longer than ERP dispersion of under the baseline state. After intravenous metoprolol, ERP dispersion is (19.2±8.3)ms, There are no significant different under the baseline state. 2) After different drugs intervention, the inducibility of artial fibrillation(AF): Total inducibility of AF is (50.15)% in S1S1 stimulating, the inducibility of AFin LSPV-D is lower than the inducibility of HRA?LA?LSPV-M?LSPV-P in S1S1 and S1S2 stimulating. After intravenous metoprolol, total inducibility of AF is (50.15)% in S1S1 stimulating. Total inducibility(67.06%)of AF in LA, HRA, LSPV is highest in intravenous Iso than in the baseline state (50.15%) and in intravenous metoprolol(48.11%) in S1S1 stimulating. After different drugs intervention, total inducibility(16.94%)of AF in LA, HRA, LSPV is highest in intravenous Iso than in the baseline state (4.09%) and in intravenous metoprolol(3.74%)in S1S2 stimulating. 3) sympathetic nerve effect on atrial fibrillation cycle length(AFCL): Bursting HRA(S1S1=100 ms)for inducing AF, AFCL is no significant different (P>0.05) in intravenous Iso than in S1S1 stimulating. AFCL is no significant different (P>0.05)in sympathetic nerve blocking state than in S1S1 stimula- ting. Bursting LA(S1S1=100 ms)for inducing AF, AFCL is more significant different (P<0.05) in intravenous Iso than in S1S1 stimulating. AFCL is no significant different (P>0.05) in sympathetic nerve blocking state than in S1S1 stimulating. Bursting LSPV in distant (-D), medial (-M) and proximal (-P) (S1S1=100ms) for inducing AF, AFCL is more significant different (P<0.01) in intravenous Iso than in S1S1 stimulating. AFCL is no significant different (P>0.05) in sympathetic nerve blocking state.Conclusion:1) Stimulating sympathetic nerve would induce the paroxysmal atrial fibrillation and persistent AF, while ERP of LA, HRA, LSPV are shorter than ERP of the baseline state; ERP of LA, HRA, LSPV are longer after sympathetic nerve was blocked, ERP dispersion of LA, HRA decrease while AF continued.2) The ERP within the pulmonary veins isn't same, such as LSPV. The ERP of LSPV-P is shorter than LSPV-D, which maybe contribute to reentry activity and atrial fibrillation. AFCL and ERP of LA, HRA, LSPV are homologous shorter, AERP is positive correlation with AFCL.3) Rapid pacing atrium and pulmonary veins would induce the paroxysmal atrial fibrillation with or without sympathetic nerve stimulating. Pulmonary veins present descending and blockade conduction, which may play bidirectional conduct role in heart conduction system.4) High sympathetic nerve tone decrease ERP of the atria and pulmonary veins, increase the dispersion and variation of ERP, which may promote the inducibility of atrial fibrillation. It suggests the effect of sympathetic nerve on electrophysiological properties and remodeling of pulmonary veins is as same as atria. Metrolol would prevent the remodeling of pulmonary veins from pulmonary venis are paced rapidly.5) The autonomic nerve blockade contribute to decrease the atrial fibrillation trigger from pulmonary veins. Both sympathetic nerve and vagal nerve are concerned with the remodeling of atria and pulmonary veins.Abstract 2 Effects of Isoproterenol on action potential and calcium current of cardiac myocytes in canineObjective: To study the effect of alkaloids of Isoproterenol (ISO) on the action potential and the calcium current in canine' s cardiac myocytes.Methods Using whole cell recording patch clamp technique, the AP and L-type calcium channel current (ICa, L) were studied in canine's atrial myocytes.Results: ISO (10nmol/L) prolonged the action potential duration (APD) and APD90 by 34. 4%, but the plateau of the action potential lowered. ISO(1μmol/L) shortened APD and APD90 by 32. 1%. ISO (10nmol/L and 1μmol/L) can induce after depolarization(EAD and DAD) and Triggered activity. ISO (10nmol/L and 1μmol/L) increased ICa, L 36. 7% and 49. 3%, respectively.Conclusion: ISO developed an enhancement effect on calcium current, and Ca2+ influx induce sarcoplasmic reticulum (SR) Ca2+ released, which probably was one of mechanisms underlying initiation of atrial arrhythmia.Abstract 3 Effects of Isoproterenol on C-reactive Protein, B-type Natriuretic Peptide of Paroxysmal Atrial Fibrillation in CanineObjective To explore the significance of C-reactive protein, B-type natriuretic peptide in the occurrence and development of atrial fibrillation(AF). Methods: The canine model of atrial fibrillation was established by rapid pacing of the upper right atrium. Blood samples were collected by jugular vein at 0 h, 4 h, 12 h, 24 h after atrial fibrillation. Radioimmunoassay and immune colorinetric method were used to measure the serum C-reactive protein, B-type natriuretic peptide levels.Results: At 12h, 24h after AF, the serum CRP levels were (7.21±1.75)mg/L and (9.78±1.80)mg/L respectively, higher than that of control group (4.21±1.92)mg/L; While there was no significant difference at hour 4 compared with control group. the serum BNP levels were (89.23±15.32)μg/L?24 h(101. 42±17.44)μg/L respectively, significantly higher than that of control group(50.12±15.97)μg/L; While there was no significant difference at hour 4 compared with control group. After ISO,at12h, 24h AF, the serum CRP levels were (10.23±1.54mg/L) and (12.13±1.74mg/L) respectively, higher than that of control group (6.32±1.56mg/L); while at 12h BNP was decreased significantly from (89.23±15.32μg/L) to (68.54±15.20μg/L).Conclusion: The serum CRPand BNP levels were significantly higher with AF continus, indicated that inflammation may contribute to AF triger and persistent. The BNP was increased at AF. ISO may increase the serum CRP levels but decrease the BNP .