Effects Of Autonomic Blockade On Cardiac Electrical Remodeling Induced By Short-term Rapid Pacing From Pulmonary Veins

Atrial fibrillation is the most common continual arrhythmia in clinic. Its morbidity will be obviously higher as age grows and it doubled every 10 years. In 50s, it is about 0.9% and up to 10% in those people above the age of 80. AF can lead to changes of cardiac electrophysiological function and these changes conduce to the onset and maintenance of AF. This course is called cardiac electrical remodeling, the abbreviation is ER. The main symptoms of ER are the decrease of atrial effective refractory period (AERP), the decrease of atrial effective refractory period frequence adaptability and increase of dispersion of effective refractory. The mechanism of ER is not well known nowadays. Generally accepted viewpoint is: the calcium overload is the priming factor of ER. The shortening of AERP and APD and the loss of AERP frequency adaptability are due to the alteration of gene expression of L-type calcium channel, Na+ channel and some kinds of potassium channels(I_to , I_ksus, I_katp). The alteration of gene expression alters the current flowof these ion channels.Automatic nervous system (ANS) plays an important role in the onset and maintenance of AF. But the effect of ANS on ER of AF is unknown and there are few researches about the impact of AF on sinus node function. By using rapid pacing canine model and blocking the ANS respectively or simultaneously , the research observes the effect on AERP, AERP frequency adaptability and sinus node function caused by nerve blocked and discuss the role of ANS in ER induced by AF, therefore it provide a new approach for prevention and reverse of AF electric remodeling.Healthy adult canines are taken as study objection. Animal models were paced through pulmonary veins rapidly to simulate acute ER induced by focal AF originated from PVs. On this base, vagus nerve and/or sympathetic nerve are blocked. The following items were observed dynamically: (1) the effect of rapid pacing on the AERP, AERP frequency adaptability, sinus node recovery time (SNRT) and corrected SNRT (CSNRT). (2) the effect of autonomic blockade on the AERP, AERP frequency adaptability, sinus node recovery time (SNRT) and corrected SNRT (CSNRT). (3) the effect of autonomic blockade on the variation of AERP, AERP frequency adaptability, sinus node recovery time (SNRT) and corrected SNRT (CSNRT) induced by rapid pacingthrough PVs.Methods: 24 healthy adult dogs were divided randomly into 4 groups: control group, atropine group, metoprolol group and atropine plus metoprolol group. First, basic atrial effective refractory period (AERP) was measured (pacing cycle length, PCL=400ms, 350ms). Secondly, stimulate pulmonary veins for ten minutes at the maximum frequency of 1:1. Then AERP was measured immediately in 0, 5,10,15 and 20 minutes respectively. When thisprotocol was finished, dogs were given a 30 minutes rest. Then, the second protocol was continued. SNRT and CSNRT were measured at baseline, and repeat after drug injection. Rapid pacing from pulmonary vein was performed for 10 minutes again, after which SNRT and CSNRT were measured again.Results: (1) Compared to control group, atropine, metoprolol and atropine plus metoprolol all prolongs AERP. Compared to control group, AERP frequency adaptability in atropine group and metoprolol group has no significant change. (2) Compared to control group, SNRT and CSNRT are shortened in atropine group but prolonged in metoprolol group atropine plus metoprolol shorten SNRT and CSNRT. (3) After 10 minutes rapid pacing, SNRT and CSNRT increased significantly in all groups, compared to pre-pacing state. (4) After 10 minutes rapid pacing, AERP, both 350ms and 400ms, were decreased if compared to pre-pacing state. (5) After 10 minutes rapid pacing, AERP frequency adaptability have significant decrease, compared to pre-pacing state. (6) Compared to control group: the degree of prolongation of SNRT in atropine group was decreased. Compared to control group the degree of prolongation of CSNRT in atropine group was decreased. (7)Compared to control group, the degree of AERP decrease in atropine group and atropine plus metoprolol group were significantly decreased. And the recovery were promoted.Conclusion: (1) The model of rapid pacing from PVs can simulate the effect of pulmonary veins originated AF on cardic electrophysiology. (2) The short-term rapid pacing for only 10 minutes from pulmonary veins resulted in the decrease of AERP and AERP frequency adaptability. Autonomic blockade could not stop this effect. (3) Vagus nerve blockade could decrease the degree of the acute atrial electric remodeling induced by short-term rapid pacing from pulmonary vein. (4) Rapid pacing for only 10 minutes alters sinus node function, result in sinus node electrical remodeling. Parasympathetic blockade...