| ObjectiveAtrial fibrillation (AF) is the most common atrial arrhythmia, which could cause hemodynamic instability, increasing mortality of heart disease patients, for instance, dilated cardiomyopathy, heart failure and myocardial infarction. Mural thrombus formation is the common complications of AF, if the thrombosis fall off would cause critical illness, such as cerebral thrombosis and pulmonary embolism. There are many classification definitions of AF, paroxysmal AF, permanent AF and chronic persistent AF often used in clinical. Paroxysmal AF with the deterioration of the illness and disease progression in delay can be developed into the persistent AF. In several studies, age susceptibility, racial differences and regional differences of atrial fibrillation have been confirmed. Incidence of atrial fibrillation in China near 0.65%, higher than international level. Therapies of AF are mainly anti-arrhythmic drugs and radiofrequency ablation, however, there is still a high recurrence rate. With the intensification of the aging process, expenditure for the treatment of AF and its associated complications will continue to rise. Therefore, the further study of AF, looking for more effective clinical treatments are very important. This part, right atrium (RA) was stimulated by three different frequencies, we analyzed the cardiac electrophysiological changes of the 3 groups, discussing if there are any differences in acute canine AF models induced by 500bpm and 1000bpm.MethodExperimental dogs were randomly divided into 3 groups. Group A:RA pacing by 500bpm, n=8; Group B:RA pacing by 1000bpm, n=8; Group C:RA pacing by the rate which 5% higher than own heartbeat, n=4. After animal anesthesia, forelimb placement and retention catheter, endotracheal intubation, non-invasive mechanical ventilation, monitoring of vital signs. Placed electrodes in heart and pulmonary vein, using Lead-7000 electrophysiology instrument stimulated and recorded electrophysiological data. Determined based and after stimulated 2h,4h,6h,8h, 10h, 12h electrophysiological data, analyzed AF induction rate, duration and effective refractory period (ERP) of the 3 groups, then calculated the dispersion of effective refractory period (dERP) between right atrial, left superior pulmonary vein (LSPV) and left inferior pulmonary vein (LIPV).ResultNineteen dogs finish the 12-hour experiment. One dog had ventricular fibrillation, drop of blood pressure, oxygen saturation decreased, with electrical cardioversion, intravenous epinephrine, rescue invalid.AF induced rate analysis:compared with RA induced rate, there was grouping effect between 3 groups, Wald χ2=81.987, P=0.000. Group A vs Group C, Wald χ2 =11.077, P=0.001; Group B vs Group C, Wald χ2=71.465, P=0.000; Group A vs Group B, Wald χ2=26.276, P=0.000. There was also time effect during 12 hours repeated measurements, Wald χ2=1138.386, P=0.000. Each time point compared with Oh of Group A,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,6h,8h, 10h and 12h showed significant difference, P<0.05. Compared with LSPV induced rate, there was grouping effect between 3 groups, Wald x2=74.383, P=0.000. Group A vs Group C, Wald χ2=13.037, P=0.000; Group B vs Group C, Wald χ2=71.808, P=0.000; Group A vs Group B, Wald x2=12.628, P=0.000. There was also time effect during 12 hours repeated measurements, Wald χ2=562.583, P=0.000. Each time point compared with Oh of Group A,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,6h,8h, 10h and 12h showed significant difference, P<0.05. Compared with LIPV induced rate, there was grouping effect between 3 groups, Wald χ2=11.374, P=0.003. Group A vs Group C, Wald χ2=0.267, P=0.605; Group B vs Group C, Wald χ2=2.718, P=0.099; Group A vs Group B, Wald x2=10.9293 P=0.001. There was also time effect during 12 hours repeated measurements, Wald χ2 =824.580, P=0.000. Each time point compared with Oh of Group A,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,4h,6h,8h, 10h and 12h showed significant difference, P<0.05.AF duration analysis:compared with RA duration, there was grouping effect between 3 groups, Wald x2=101.069, P=0.000. Group A vs Group C, Wald x2=41.633, P=0.000; Group B vs Group C, Wald χ2=101.036, P=0.000; Group A vs Group B, Wald χ2=3.680, P=0.055. There was also time effect during 12 hours repeated measurements, Wald χ2=2292.418, P=0.000. Each time point compared with Oh of Group A,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,4h,6h, 8h, 10h and 12h showed significant difference, P<0.05. Compared with LSPV duration, there was grouping effect between 3 groups, Wald χ2=82.645, P=0.000. Group A vs Group C, Wald χ2=20.431, P=0.000; Group B vs Group C, Wald x2 =80.467, P=0.000; Group A vs Group B, Wald χ2=4.843, P=0.028, There was also time effect during 12 hours repeated measurements, Wald χ2=3357.463, P=0.000. Each time point compared with Oh of Group A,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h, 6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Compared with LIPV duration, there was grouping effect between 3 groups, Wald x2 =11.806, P=0.003. Group A vs Group C, Wald χ2=3.418, P=0.064; Group B vs Group C, Wald x2=11.799, P=0.001; Group A vs Group B, Wald χ2=1268, P=0.260. There was also time effect during 12 hours repeated measurements, Wald χ2=1344.760, P=0.000. Each time point compared with Oh of Group A,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B, 2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05.ERP analysis:compared with RA ERP, there was grouping effect between 3 groups, Wald χ2=200.818, P=0.000. Group A vs Group C, Wald x2=30.563, P=0.000; Group B vs Group C, Wald χ2=192.706, P=0.000; Group A vs Group B, Wald χ2 =35.928, P=0.000. There was also time effect during 12 hours repeated measurements, Wald χ2=881.937, P=0.000. Each time point compared with Oh of Group A,2h,4h, 6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Compared with LSPV ERP, there was grouping effect between 3 groups, Wald χ2=13.599, P=0.001. Group A vs Group C, Wald x2=1.506, P=0.220; Group B vs Group C, Wald x2=10.472, P=0.001; Group A vs Group B, Wald x2=9.625, P=0.002. There was also time effect during 12 hours repeated measurements, Wald x2=825.339, P=0.000. Each time point compared with Oh of Group A,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, lOh and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,2h,4h, 6h,8h, 10h and 12h showed significant difference, P<0.05. Compared with LIPV effective refractory period, there was no grouping effect between 3 groups, Wald χ2 =1.893, P=0.388. There was also time effect during 12 hours repeated measurements, Wald χ2=1249.679, P=0.000. Each time point compared with Oh of Group A,2h,4h, 6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05.Analysis of dERP:there was grouping effect between 3 groups, Wald x2=27.342, P=0.000. Group A vs Group C, Wald χ2=26.575, P=0.000; Group B vs Group C, Wald χ2=10.975, P=0.001; Group A vs Group C, Wald χ2=0.324, P=0.569. There was also time effect during 12 hours repeated measurements, Wald χ2=18.363, P=0.005. Each time point compared with Oh of Group A, 10h showed significant difference, P<0.05. Each time point compared with Oh of Group C,2h,4h,6h,8h, 10h and 12h showed significant difference, P<0.05.Conclusion(1) Atrial fibrillation were successfully induced by 3 kinds of pacing, and caused different degrees of atrial electrical remodeling. The induction rate and duration time of AF showed an increasing trend with the prolonging of time. In 12 hours stimulation, ERP general showed shorten trend, the shortest ERP showed during 6-hour to 10-hour, then showed extension of a certain degree.(2) RA pacing by 1000bpm stimulation caused more significant electrophysiological changes than 500bpm pacing and 5% higher than own heartbeat pacing. In addition to this change of atrial electrical remodeling, there may be involved in nerve reconstruction. Speculated that different level neuroplasticity caused by different pacing way, and 1000bpm was significantly. The Second Part ANS Change of Acute Canine AF Model Induced by Frequencies Dependent Electrical Stimulation ObjectHeart is regulated by the external autonomic nerve and inner autonomic nerve. Autonomic nerve system (ANS) consists of sympathetic nerve and vagus nerve. A large number of studies have shown that ANS plays an important role in AF. Noradrenaline (NE) and acetylcholine (Ach) as the main neurotransmitter of ANS play a regulating function of heart. Acute animal experiments suggest the neurotransmitter concentrations has time-dependent. Clinical studies have confirmed that normal levels of NE and Ach are different with AF patients. This part mainly determined neurotransmitter contents during the experimental process in serum and myocardial tissue, combined with the neural signal analysis results which we recorded from the experiment. Discussed the difference of neural reconstruction between the 3 groups.MethodExperimental dogs were randomly divided into 3 groups. Group A:RA pacing by 500bpm, n=8; Group B:RA pacing by 1000pm, n=8; Group C:RA pacing by the rate which 5% higher than own heartbeat, n=4. After animal anesthesia, forelimb placement and retention catheter, endotracheal intubation, non-invasive mechanical ventilation, monitoring of vital signs. Placed electrodes in heart and pulmonary vein, using Lead-7000 electrophysiology instrument stimulated and recorded electrophysiological data. Determined based and after stimulated 2h,4h,6h,8h, 10h, 12h electrophysiological data, analyzed AF induction rate, duration and ERP of the 3 groups, then calculated the dERP between right atrial, LSPV and LIPV.Tested NE and Ach contents of peripheral venous blood, base and after stimulated 1h,2h,3h,4h,5h, 6h,7h,8h,9h, 10h,11h and 12h, also tested neurotransmitter contents in the RA organization at the end of 12 hours stimulation.ResultsSerum level of NE analysis:there was no grouping effect between 3 groups, Wald χ2=5.555, P=0.062. There was also time effect during 12 hours repeated measurements, Wald χ2=119.689, P=0.000. Each time point compared with Oh of Group A,3h,4h,5h,8h,9h and 10h showed significant difference, P<0.05. Each time point compared with Oh of Group B, 1h,2h,3h,4h,5h,8h,11h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C,2h,3h, 4h and 5h showed significant difference, P<0.05.Serum level of Ach analysis:there was grouping effect between 3 groups, Wald χ2=13.913, P=0.001. Group A vs Group C, Wald χ2=0.097, P=0.755. Group B vs Group C, Wald χ2=6270, P=0.012. Group B vs Group A, Wald x2=11-029, P=0.001. There was also time effect during 12 hours repeated measurements, Wald x2=28.388, P=0.005. Each time point compared with Oh of Group A, 1h,2h,3h,4h,5h,6h,7h,8h and 9h showed significant difference, P<0.05. Each time point compared with Oh of Group B, 1h,2h,3h,4h,5h,6h,8h, 10h, 11h and 12h showed significant difference, P<0.05. Each time point compared with Oh of Group C, 1h,3h,4h,5h,6h, 10h, 11h and 12h showed significant difference, P<0.05.Compared NE and Ach of right atrial tissues:there was grouping effect of noradrenaline between 3 groups, Group A, Group B vs Group C showed significant difference, P<0.05. Group B vs Group A showed significant difference, P<0.05. There was grouping effect of acetylcholine between 3 groups, Group B vs Group A, Group C showed significant difference, P<0.05, Group A and Group C was no difference, P>0.05.Conclusion(1) The 3 groups serum levels of NE and Ach shown different changes and these kinds of changes seem to have time dependence. It was suggested that serum levels of NE and Ach may show AF duration and ANS action when the AF was onset.(2) 1000bpm shown significant changes in both serum and myocardial tissue, prompted that the mechanism of AF induced by 1000bpm was closely related to neural activation.(3) Compared with neural signals analysis which recorded in preliminary experiment, serum levels of neurotransmitter could match the signal change in 500bpm and 1000bpm stimulation.(4) AF induced by 500bpm was based on atrial electrical remodeling, AF induced by 1000pm was based on atrial electrical remodeling and ANS remodeling, suggested that treatment plan of recover ANS balance should be considered when clinical treat a patient of fast frequency AF.The Third PartRAS Change of Acute Canine AF Model Induced by Frequencies Dependent Electrical StimulationObjectRenin-angiotensin system (RAS) as an important neurohormonal endocrine system, involved in the development and maintenance of various diseases, such as hypertension, myocardial infarction and heart failure. Numerous studies confirm that angiotensin Ⅱ (Ang II), angiotensin Ⅱ type 1 receptor (ATiR) and angiotensin II type 2 (AT2R) receptor play an important role in the course of AF, participate in atrial remodeling, promoting fibrosis and inflammatory factor and so on. The major research of this part, we tested renin and Ang Ⅱ concentrations of myocardial tissue and serum. Tested proteins and RNA expression of angiotensin receptor 1 and angiotensin receptor 2. Discussed the renin-angiotensin system activation level of three different frequency electrical stimulation.MethodExperimental dogs were randomly divided into 3 groups. Group A:RA pacing by 500bpm, n=8; Group B:RA pacing by 1000bpm, n=8; Group C:RA pacing by the rate which 5% higher than own heartbeat, n=4. After animal anesthesia, forelimb placement and retention catheter, endotracheal intubation, non-invasive mechanical ventilation, monitoring of vital signs. Placed electrodes in heart and pulmonary vein, using Lead-7000 electrophysiology instrument stimulated and recorded electrophysiological data. Determined based and after stimulated 2h,4h,6h,8h, 10h, 12h electrophysiological data, analyzed AF induction rate, duration and ERP of the 3 groups, then calculated the dERP between right atrial, LSPV and LIPV. Tested renin and Ang Ⅱ contents of peripheral venous blood, base and after stimulated 1h,2h,3h, 4h,5h,6h,7h,8h,9h, 10h, 11h and 12h, also tested renin, Ang Ⅱ, AT1R and AT2R proteins and RNA expression of right atrium organization at the end of 12 hours stimulation.ResultsSerum level of renin analysis:there was grouping effect between 3 groups, Wald X2= 25.018, P=0.000. Group A vs Group C, Wald x2= 0.066, P=0.797; Group B vs Group C, Wald x2=18.524, P=0.000; Group B vs Group A, Wald x2= 9.546, P=0.002. There was also time effect during 12 hours repeated measurements, Wald x2=37.132, P=0.000. Each time point compared with Oh of Group A, 1h,2h,3h,4h,5h,6h,9h, 10h and 11h showed significant difference, P<0.05. Each time point compared with Oh of Group B,2h,3h,4h,7h,8h,11h and 12h showed significant difference, P<0.05. Each time point compared with Oh of group C,4h showed significant difference, P<0.05.Serum level of Ang Ⅱ analysis:there was no grouping effect between 3 groups, Wald x2=2.426, P=0.297. There was also time effect during 12 hours repeated measurements, Wald x2=356.198, P=0.000. Each time point compared with Oh of Group A,3h,4h,5h,6h,7h,8h,9h, 10h, 11h and 12h showed significant difference, P<0.05.Each time point compared with Oh of Group B, 1h,2h,3h,4h,5h,6h,7h,9h, 10h, 11h and 12h showed significant difference, P<0.05. There was no time effect in Group C,P>0.05。Compared renin, Ang Ⅱ, AT1R and AT2R proteins expression of RA tissue: compared with Group C, renin, Ang Ⅱ, AT1R and AT2R proteins expression of Group A and Group B had significant difference, P=0.000. Compared Group B with Group A, there was also significant difference, P=0.000.Compared renin, Ang II, AT1R and AT2R RNA expression of RA tissue: compared with Group C, renin and Ang II RNA expression of Group A and Group B had significant difference, P<0.05. There was also significant difference between Group A and Group B, P<0.05. Compared with Group B, AT1R RNA expression of Group A and Group C had clearly difference, P<0.05. There was no significant difference between Group A and Group B, P>0.05. Compared with Group C, AT2R RNA expression of Group A and Group C did not have significant difference, P>0.05, but, there was significant difference between Group B and Group A, P<0.05.Conclusion(1) RAS changes caused by 1000pm pacing were more significant than 500bpm pacing and 5% higher than own heartbeat pacing.(2) The serum level of renin got time-dependent. The renin and Ang Ⅱ contents of serum and myocardial were not match very well, that may caused by local renin-angiotensin system and enzymatic reaction.(3) Translation and expression of ATiR and AT2R were different between 500bpm and 1000pm, prompted that Ang Ⅱ receptors had different changes with different frequency pacing. |
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