Research On Detection Method, Mechanism And Medicine Interference Of Right Atrium In Chronic Atrial Fibrillation

Backgroud: Atrial fibrillation (AF) is always considered to be a left atrium associated disease. With the development of the research on the mechanism of AF and the advancement of radio-frequency ablation, attention was paid to the role of right atrium in the occurrence and maintenance of AF. Due to the methodology, however, the research on the structure, function and hemodynamics of right atrium remained relatively less than left atrium in any pathophysiologic state. Thus, it was necessary to approach new methods to study right atrium.Right atrium, similar to left atrium, has three main functions. First, it is just like a conservator that can collect and store the blood from superior and inferior vena cava during the systolic stage. Second, it works as a conduit that can transport the blood from vena cava to right ventricle during the early diastolic stage. Third, it is like a pump that can enhance ventricular filling at the late diastolic stage .In short, right atrium plays an important role in regulating right ventricular filling and maintaining global cardiac output at all pathologic and physiological stages. Right atrial special structures and the changes of matrix are closely related with the occurrence and development of arrhythmias.Atrial pressure-volume (area) relationship was considered the most exact and representative index that could reflect the changes of atrial functions and hemodynamics. Furthermore, acquirements of atrial pressure by catheterization being invasive, most data were obtained from animal experiments. Yet, echocardiography served as a non-invasive method to evaluate atrial structure, function and hemodynamics. So the research about atrium transits from experiment to clinic. According to automatic edge detection principle, acoustic quantification echnique could real-time display cavity area-time curve, capacity-time curve and differential curve .So AQ technique could non-invasively evaluate left atrial function. Nevertheless, whether AQ technique could evaluate right atrial structure, function and hemodynamics has not been reported.Primary pulmonary artery hypertension results in right ventricular dysfunction. While right atrium played an important role in maintaining right ventricular filling when right ventricle was in dysfunction. Hypertension could cause dysfunction of left ventricle and non-valvular atrial fibrillation, and the influence of hypertension on right heart system was unknown yet. Dernellis et al. found that patients with primary hypertension had impaired right atrial function by measuring tricuspid blood flow with pulsed wave Doppler. Yet, AQ technique evaluating right atrial structure, function in patients with primary pulmonary hypertension or primary hypertension has not been reported so far.Objectives: (1)To investigate the feasibility of AQ technique to evaluate right atrial function; (2)To observe the changing of right atrial structure and function in patients with pulmonary artery hypertension; (3)To determine the changing of right atrial structure and function in patients with primary hypertension.Methods: Subjects: Eighty-seven patients were included in this study. (l)Twenty of them were in control group including nine males and eleven females (average 35.21±14.60 years old), and they had no history of cardiovascular diseases and their examination results of laboratory examination, EKG and echocardiography were normal.(2) Seventeen patients with pulmonary hypertension, including six males and eleven females (average 38.82±13.43 years old), were enrolled in this experiment. Seven of them had primary pulmonary hypertension or pulmonary vascular diseases, ten with congenital heart diseases. And their diagnoses were made by echocardiography, surgery or CT examination. Also, they had no other heart associated diseases such as hypertension, coronary heart disease and diabetes.(3) The rest were fifty hypertensive patients that were excluded with secondary hypertension, graded I or II class, including thirty-five males and fifteen females (average 52.24±6.86 years old). Their blood pressure met the criteria of WHO/ISH hypertension diagnosis, which was diastolic pressure≥90mmHg ( 1mmHg =0.133Kpa) and systolic pressure≥140 mmHg .And the history of diseases was 0.5-32 years (average 12.81±10.3 years).Experimental approach: The patients, quietly breathing, underwent echocardiographic evaluation in the left recumbent position, including M mode, 2-D, Doppler, and AQ curves, which were simultaneously accompanied with II lead electrocardiogram recorded. The averages were obtained by calculating them in all patients over 3-5 cardiac cycles. (1) M-mode and two-dimensional echocardiography: Parasternal long axis view and apical four-chamber view were taken. (2)Tricuspid flow frequency spectrum: Transtricuspid flow profile was assessed by 2-D guided continuouswave Doppler from the apical 4-chamber view by positioning a 3-mm-sized sample volume between the tips of the tricuspid leaflets in diastole and recording at a sweep velocity of 100 mm/s. Then pulmonary systolic pressure was estimated. (3)Superior vena flow spectrum: After the apical four-chamber view being taken, PW sampling volume, guided by color Doppler, was positioned at about 1cm inside superior vena entrance level to get superior vena cava best flow spectrum. (4)Right atrial volume curve: When apical four-chamber view being well displayed, second harmonic imaging, automatically average and AQ system were started, then the control button of total gain, time gain compensation (TGC) and lateral gain compensation (LGC) were regulated to make AQ curve closely aligning with right atrial endocardium and draw total right atrial interested region. AQ technique could real-time display right atrial volume-time curve and its differential curve.Parameters: Parameters of M-mode and two-dimensional echocardiography:(1)right ventricular anterior wall thickness (RVAM, mm); (2)interventricular septal thickness (IVS, mm); (3)right ventricular end diastolic diameter (RVED, mm); (4)right atrial length (RAL, mm) and transverse diameter (RAT, mm); (5)right ventricular ejection fraction (RVEF). Parameters of Doppler echocardiography: (1) transtricuspid E/A ratio; (2) Reverse A wave peak velocity of superior vena frequency spectrum (Ar, cm/s);(3) pulmonary arterial systolic pressure (mmHg). Parameters of right atrial volume curve: (1)right atrial volume at right ventricular end-diastolic stage (EDV, ml); (2)right atrial volume at right ventricular end-systolic stage (ESV, ml); (3)right atrial end-rapid emptying volume (EREV, ml);(4)right atrial rapid emptying volume (RE, ml): RE=ESV-EREV; (5)right atrial active contraction emptying volume (AE, ml): AE=EREV-EDV; (6)right atrial reservoir volume (RV, ml): RV=ESV-EDV, also RV is right atrial total emptying volume; (7)right atrial rapid emptying fraction (REF, %): REF=RE/RV×100%; (8)right atrial active contraction emptying fraction (AEF, %): AEF=AE/RV×100%; (9)peak filling rate (PFR, ml/s); (10)peak rapid emptying rate (PRER, ml/s); (11) peak atrial emptying rate (PAER, ml/s); (12)PRER/PAER.Results: The changes of right atrial functions in patients with pulmonary hypertension: (1) Results of two dimensional and Doppler echocardiography: Compared with control subjects, RVAW, IVS, RVED and right atrial inner diameter were increased significantly (P<0.05～0.01) and right ventricular systolic function was significantly decreased (P<0.001) in patients with pulmonary hypertension. And A wave peak flow velocity of superior vena cava flow spectrum was significantly increased (P<0.001). The pulmonary arterial systolic pressure was 93.81±22.88 mmHg in patients with pulmonary hypertension. (2)The results detected by AQ technique: Compared with control subjects, the parameters which could reflect the changes of volume, such as ESV, EDV, EREV and AE, were significantly increased (P<0.05～0.01) in patients with pulmonary hypertension, and right atrial RV and PFR were increased significantly (P<0.05-0.01). And REF of right atrium was significantly decreased (P<0.05). Yet PRER had no significant difference (P>0.05). AEF and PAER of right atrium were significantly increased (P<0.05～0.01) in patients with pulmonary hypertension.The changes of right atrial functions in patients with primary hypertension: (1) Results of two dimensional and Doppler echocardiography: Compared with control subjects, RVAW and IVS were significantly increased (P<0.01) and tricuspid flow frequency spectrum showed E/A<1 in patients with primary hypertension. (2) The results detected by AQ technique: Compared with control subjects, the parameters which could reflect the changes of volume, such as ESV, EDV, EREV, RE and AE, were significantly increased (P<0.05-0.01) in patients with primary hypertension. And right atrial RV and PFR were increased significantly (P<0.01). Yet PEF, AEF and PRER of right atrium had no significant difference (P>0.05). PRER/PAER was decreased significantly (P<0.01) and PAER was increased significantly (P<0.01).Conclusions: (1) Acoustic quantification technique can non-invasively evaluate right atrial structural and functional changing under the conditions of pathophysiology. (2) In patients with pulmonary hypertension atrial structure and functions altered significantly, including dilated right atrium, impaired right atrial conduit function and compensatory enhancement of right atrial booster pump and reservoir functions, to facilitate right ventricular filling. (3) In hypertensive patients significant alterations of atrial structure and functions consist of dilated right atrium, decreased right atrial conduit function and compensatory enhancement of right atrial booster pump and reservoir functions. Background: Non-drug therapy to atrial fibrillation (AF) has been a hot spot in electrophysiological fields recently. With the development of pulmonary vein electric isolation aiming at triggering foci and atrial linear ablation around pulmonary vein aiming at the matrix maintaining AF, the success rate of treating AF with radiofrequency catheter ablation has been greatly increased since 1998 especially 2002. At present, the achievement rate of treating paroxysmal AF with radiofrequency ablation stays from 80% to 90%, but the achievement rates of treating persistent AF and permanent AF are still lower and a certain recurrent rate is also existent, as well as a low long-term achievement rate, yet the morbidity of chronic persistent AF is significantly higher than paroxysmal AF. Therefore, how to improve the achievement rate of treating chronic persistent AF with radiofrequency ablation is widely concerned and then the mechanism of AF becomes a hot spot. Recently Yamane etc. has reported a case of AF which originated from superior vena cava and was successfully cured with radiofrequency ablation. Crista terminalis is an important source of some AF. Some study showed that there were two regions of unidirectional block on the posterior border of crista terminalis and demarcation between crista terminalis and pectinate muscles, so reentrant cycle formed to cause atrial flutter as the electricity conduction of right atrium couldn't track the block regions. If the range of blocking region became smaller, the reentrant cycle would then become smaller and instable, and diffuse around to result in atrial fibrillation. Consequently, right atrium played an important role in the occurrence of AF.The experimental and clinical research confirmed that the structure remodeling of left atrium played an important role in maintaining AF. Further study revealed that isolating pulmonary vein and the left atrial posterior wall around that (pulmonary vein vestibulum) by radiofrequency ablation would dramatically improve the success rate of curing AF patients with anatomical heart diseases. However, whether AF could cause right atrial structural remodeling was unknown yet. And if right atrial structural remodeling was serious to some extent, right atrial matrix remodeling itself could maintain AF. So AF couldn't be eliminated by treating left atrium alone with radiofrequency ablation, which might be one of the reasons for so low success rate of treating chronic AF at present.The research on left atrial structural remodeling in patients with AF confirmed that the main components of atrial remodeling were the fibrosis of atrial myocardial extracellular matrix and atrial enlargement. Matrix metalloproteinase-9 (MMP-9) and its endogenous tissue inhibitor of metalloproteinase-1 (TIMP-1) were important protease systems that regulate the synthesis and degradation of extracellular matrix collagen. Lately the research on patients with AF showed that the alterations of MMPs/ TIMPs expression were associated with atrial myocardial extracellullar matrix remodeling and atrial enlargement. However, whether the alterations of MMPs/ TIMPs expression were the mechanism of right atrial structural remodeling remained unclear. At present, little is known about the factors regulating and influencing MMPs/TIMPs in AF patients. Previous studies confirmed that the activation of renin-angiotensin system (RAS) and intracellular calcium (Ca²⁺ ) overload were the basic pathophysiological mechanisms of electrical and structural remodelings in AF. As a result, it suggested that the activation of RAS and intracellular Ca²⁺ overload might be important pathways of activating MMPs/ TIMPs during AF.In recent years, a series of clinical studies showed that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) could prevent AF to a certain extent by inhibiting RAS, but its mechanism has not been elucidated yet. This study investigated the effects of ACEI on the expression of MMPs/TIMPs and its effects on atrial structural remodeling through administration of ACEI on the animal models with AF. Also, it provided a theoretical basis for preventing and treating AF with non-traditional anti-arrhythmic drugs. The first part of this topic has confirmed the feasibility of evaluating right atrial structural and functional changes by AQ technique, but the application of AQ technique to evaluate the changes of right atrium in animals with AF has not been reported.Objectives: (1)To evaluate the dynamic changes of right atrial structure and functions using echocardiography and AQ technique in the process of establishing animal models with AF; (2)To observe the changes of right atrial ultrastructure and extracellular matrix; (3)To detect the effects of RAS activation on right atrial structural remodeling; (4)To determine the effects of MMP-9/TIMP-1 on right atrial structural remodeling; (5)To investigate the regulating effects of RAS activation and intracellular Ca²⁺ overload on MMP-9/TIMP-1; (6)To explore the parallel relationship between molecular biological changes and right atrial structural and functional changes; (7)To observe the influence of ACEI on MMP-9/ TIMP-1 of right atrium; (8)To assess the protective effect of ACEI on right atrial structure.Methods: (1) First, dog models with chronic atrial fibrillation were estabalished by rapid atrial pacing. (2) The changes of right atrial area and mitral, tricuspid refluxing and refluxing degree were monitored by echocardiography before pacing and after rapid atrial pacing for 1 week, 4 weeks and 8 weeks. (3) Right atrial pressure was monitored before and after rapid atrial pacing. (4) Right atrial myocardium AngII was determined by radioimmunoassay. (5) Intracellular Ca²⁺ concentration in right atrial myocardium was detected by three-electrode DC plasma photoelectric spectrometry. (6) The structure and collagen content of right atrial myocardium were observed and quantified by conventional HE and Masson staining. (7) The ultrastructure of right atrial myocardium was observed using transmission electron microscopy (TEM). (8) The mRNA expressions of ACE, MMP-9 and TIMP-1 were determinded by reverse transcription polymerase chain reaction (RT-PCR) in right atrial myocardium. (9) The protein levels of MMP-9 and TIMP-1 were analyzed by western blot. (10) The spatial distributions of MMP-9 and TIMP-1 were determined by immunohistochemistry.Results:(1) The establishment of animal models with AF: One dog of rapid atrial pacing group was dead after 12 hours, and the autopsy found that the electrode in right atrial appendage entered into right ventricle, suggesting that the cause of its death was ventricular fibrillation by rapid pacing. Four weeks after surgery, another dog manifested abdominal distension and sign of ascites was positive. And its food intake and action were decreased obviously. Ultrasonic examination found that one 26mm×21mm low density echogenic mass at the top of atrial electrode and there were a lot of pleural effusion and ascites. The autospy confirmed that the cause was thrombogenesis at the top of electrode. Eight weeks after surgery, another dog's pacemaker stopped releasing pulse when ECG examination was taken. One dog in treating group was dead because the pacing electrode entered ventricle causing ventricular fibrillation. So the four dogs mentioned above were not included in this experiment. Eventually, pacing group and treatment group each had 8 dogs completed the entire experiment. Before rapid atrial pacing, AF could not been provoked among all dogs by programming stimulation and/or burst stimulation. After this experiment AF was not provoked among 6 dogs in control group by programming stimulation and /or burst stimulation. Two dogs of pacing group respectively emerged paroxysmal AF at 1 week and 4 weeks after rapid atrial pacing. Electrophysiologic examination was carried out at 8 weeks after rapid atrial pacing, two dogs (25%) emerged spontaneous AF; AF were provoked among 4 dogs (50%)by programming stimulation, among 2 dogs (25%) by burst stimulation. It suggested that we had successfully established chronic AF models. One dog of treatment group emerged paroxysmal AF at 1 week after operation, two dogs emerged AF by programming stimulation at 8 weeks after pacing, and the other 6 dogs did not emerged AF by programming and burst stimulation. (2)Echocardiographic data comparison: â‘ The influence of rapid atrial pacing on atrial diameter: One week after pacing, right atrial areas were extremely significantly increased (P<0.001) compared with that before pacing in pacing group and the inner diameter was further increased with time going on. Eight weeks after pacing, the inner diameter was significantly increased (P<0.05) compared with that of 1 week after pacing, and there was no difference compared with that of 4 weeks after pacing (P>0.05). And right atrial areas of pacing group were extremely significantly increased after pacing 1, 4, 8 weeks compared with those of control group at the same time respectively (P<0.001). One and four weeks after pacing, right atrial areas of treatment group trended to enlarge compared with those of control group before pacing, but the difference had no significance(P>0.05), and compared with pacing group, right atrial areas of treatment group were significantly decreased (P<0.01～0.001). Eight weeks after pacing, right atrial areas of treatment were significantly decreased (P<0.001) compared with pacing group, but significantly increased compared with control group (P<0.05).â‘¡ The influence of rapid atrial pacing on mitral and tricuspid flow frequency spectrum: Color Doppler showed that mitral and tricuspid regurgitations took place in pacing groups in the process of pacing and it was more serious with the pacing time increased. And only one dog in control group had light mitral regurgitation in the experiment. Eight weeks after pacing, eight dogs in AF group had moderate-heavy mitral regurgitations and 8 dogs had light-moderate tricuspid regurgitations. And 4 dogs in treatment group had mitral regurgitations (light～moderate) and tricuspid regurgitations (3 dogs, light), the degree was lighter than that of AF group.â‘¢ The influence of rapid atrial pacing on right atrial volume: Compared with control group, ESV, EDV and EREV of AF group began to increase and EF and CV were decreased (P<0.05) 4 weeks after pacing, and ESV, EDV and EREV were significantly increased (P<0.001), while EF and PAER decreased significantly (P<0.001) and also CV was decreased significantly (P<0.05) 8 weeks after pacing, the other parameters had no significant changes in pacing progress. In atrial fibrillation group, compared with before pacing, right atrial AQ parameters each had no significant changes 1 week after pacing (P>0.05); ESV, EREV and EDV were significantly increased (P<0.05) and EF was significantly decreased (P<0.05) 4 weeks after pacing, and ESV, EREV and EDV were significantly increased (P<0.001) while EF and PAER were significantly decreased (P<0.001) 8 weeks after pacing. Compared with 1 week after pacing, ESV, EREV and EDV were significantly increased (P<0.01) and EF and PAER was significantly decreased (P<0.01) 8 weeks after pacing. And other parameters had no statistical significance. However, eight weeks after pacing, the increase of ESA, ESV, EDV and EREV and the decrease of EF in treatment group were less than those in pacing group (P<0.05). It suggested that captopril had significant protection on atrial structural and functional changes such as atrial enlargement, increased volume and decreased contraction caused by atrial rapid pacing. (3)The influence of rapid atrial pacing on right atrial pressure: Before rapid atrial pacing, there was no statistical significance between right atrial pressure in AF group and that in control group(3.17±2.52 mmHg VS 4.95±3.24 mmHg, P>0.05). Eight weeks after pacing, right atrial pressure in AF group was significantly increased compared with control group (7.09±1.13 VS 4.50±1.51 mmHg, P<0.01) , and right atrial pressure in treatment group was significantly decreased compared with that in AF group (5.28±1.96 mmHg VS 7.09±1.13 mmHg, P <0.05) , but was still higher than that in control group (5.28±1.96 mmHg VS 4.95±3.24 mmHg, P>0.05 ) . (4)The changes of intracellular calcium concentration in right atrial myocardium: Compared with control group, intracellular calcium concentration in right atrial myocardium was significantly increased by 36.18% in AF group (37.68±10.45 ug/mg VS 27.67±4.46 ug/mg, P<0.05). And compared with pacing group, calcium concentration was significantly decreased in treatment group (29.88±1.47 ug/mg VS 37.68±10.45 ug/mg, P<0.05), and it was still higher than that in control group(29.88± 1.47 ug/mg VS 27.67±4.46 ug/mg, P>0.05) . (5)Angiotensin II content of right atrial myocardium: Compared with control group, the concentration of AngII in right atrial myocardium was significantly increased by 51.94% (11.38±3.77 pg/mg VS 7.49±1.65 pg/mg, P<0.05) in AF group. And compared with AF group, the concentration of Angll in right atrial myocardium was significantly decreased in treatment group (7.12±1.01 pg/mg VS 11.38±3.77 pg/mg, P<0.05) ,and it was a little lower than that in control group (7.12±1.01 pg/mg VS 7.49±1.65 pg/mg, P>0.05 ) . (6) Structural changes of right atrial myocardium: Atrial myocardium sections from controls showed normally structured cardiomyocytes, which were surrounded by a small amount of connective tissue. The nuclei were big and legible. Connective tissue network was in the myocardia. Yet fibroblasts in the interstice were regular-sized and moderate-numbered. Sections from AF dogs showed enlarged myocardia were disarranged, the nuclei were in irregular size and obvious heteromorphism. Some myofilaments were disrupted and collagen tissues were accumulated among the myofilaments to broaden the gaps between cardiomyocytes. The amount of myofibroblasts in interstitium was increased. In treating dogs the structure of atrial myocardium was almost the same as that in control except for a slight rise in the amount of connective tissue. Masson stain showed that collagen tissue was appropriate arranged among cardiomyocytes in controls. The appearance of the connective tissue framework of the myocardium was unchanged. Samples from AF dogs showed, however, that collagen tissue disarranged and disrupted in some area increased markedly. While in treating dogs collagenous fibers were slightly increased and disarranged, but exhibited an intact collagen network. The quantitative analysis showed that the content of collagen in right atrial myocardium was significantly increased in AF group compared with control group (27.75±7.83 VS 19.23±3.67, P<0.05). Compared with AF group, the content of collagen in right atrial myocardium was significantly decreased in treating group (20.47±3.99 VS 27.75±7.83, P<0.05), but it was still higher than that of control group (20.47±3.99 VS 19.23±3.67,P>0.05). (7) Ultrastructural changes of atrial myocardium: â‘ At the ultrastructural level, atrial myocytes from controls showed a highly organized sarcomeric structure with rows of uniform-sized mitochondria between them.â‘¡The myofibrillae in myocardium were arranged regularly with no ruptur.â‘¢ The mitochondria were enlarged and considerable, and the cristae were tightly arranged like 'Z' shape. â‘£ The sarcoplasmic reticulum were in large size and a large number. ⑤ The endochylema was enriched.â‘¥A typical distribution of heterochromatin in the form of clusters at the nuclear memrane was present in all cardiomyocyte nuclei. The nucleoli can be easily observed.⑦Intercalated disc were normally structured.⑧ Atrial granules were mainly confined to the perinuclear area. Atrial myocytes from AF dogs showed characteristic changes as below: â‘ Contractile material was depleted (myolysis). The myofibrillae in myocardium were arranged irregularly with ruptures. The disapperance of sarcomeres was often limited to the vicinity of the nuclei but also frequently involved the entire cytosol, in which only fragments of sarcomeres were present.â‘¡Typical changes in size and shape of mitochondria were seen in area depleted of sarcomeres. Many mitochondria had become elongated and in different sizes. The cristae were arranged along the long axis. â‘¢The sarcoplasmic reticulum became swelling, disrupted, and decreased in number. â‘£The nuclear membrane was not smooth and the segmented nucleus could be seen. And the heterochromatins were dispersed uniformly throughout the nucleoplasm. ⑤ Intercalated discs were discontinued and indistinct.â‘¥Huge amount of glycogen accumulated the myolytic space in almost all cells that underwent myolysis, even formed "glycogen lake" . ⑦ Atrial granules were increased and scattered widely. Similar atrial myocytic structures were observed in treating dogs with alterations intermediate between the two groups above. (8)The mRNA transcription level of atrial myocardium: â‘  Compared with control group, the level of ACE mRNA of right atrial myocardium increased by 45.00% in AF group (0.29±0.08 VS 0.20±0.01, P<0.05), and compared with AF group, the level of ACE mRNA of right atrial myocardium trended to decrease in treatment group, but the difference had no statistical significance (0.27±0.07 VS 0.29±0.08, P>0.05) .â‘¡Compared with control group, MMP-9 mRNA of right atrial myocardium increased by 109.09% and the transcription level of TIMP-1 mRNA increased by 71.43% in AF group(MMP-9: 0.23±0.04 VS 0.11±0.009; TIMP-1: 0.12±0.02 VS 0.07±0.01, P<0.01), and MMP-9/TIMP-1 trended to decrease but had no statistical significance(1.99±0.68 VS 1.53±0.26, P>0.05) . Compared with AF group, MMP-9 mRNA in treatment group was significantly decreased (0.19±0.03 VS 0.23±0.04, P<0.05) , but the level of TIMP-1 mRNA had no significant changes (0.12±0.03 VS 0.12±0.02, P>0.05) , still it was higher than that of control group (0.12±0.03 VS 0.07±0.01, P<0.01) . (9)The western blot and immunohistochemical staining results of MMP-9 and TIMP-1: Compared with control group, the protein expression level of MMP-9 in right atrial myocardia was significantly increased in AF group (115.38±22.07 VS 84.75±20.32, P<0.05) . Compared with AF group, the protein expression level of MMP-9 in right atrial myocardia was significantly decreased in treatment group (90.37±18.50 VS 115.38±22.07. P<0.05). Compared with control group, the protein expression level of TIMP-1 trended to decrease in right atrial myocardia, but there was no statistical significance (99.38±17.10 VS 105.63±21.07,P>0.05) .And compared with AF group, the protein expression level of TIMP-1 in right atrial myocardia also had no statistical significance (103.94±15.02 VS 99.38±17.10, P>0.05) .To further determine the intracellular expression and histological locating characters of MMP-9 and TIMP-1, MMP-9 and TIMP-1 monoclonal antibodies were used to detect their expressions and cellular localization by immunohistochemical method. The result revealed that MMP-9, irregular reticular sparse brown granules, which were evenly-distributed in myocardial cytoplasm in control group and that MMP-9, irregular reticular brown granules, which were densely-distributed in myocardial cytoplasm in AF group. And TIMP-1, irregular reticular brown granules, which were evenly-distributed in myocardial cytoplasm in control group, but irregular reticular relative-sparse brown granules in AF group. MMP-9, irregular reticular sparse brown granules which were evenly-distributed in myocardial cytoplasm in treatment group and the distribution of TIMP-1 in myocardial cytoplasm in treatment group was the same as that in control group. (10)The relationships between molecular biological parameters and ultrasonic, hemodynamic parameters: Linear correlation analysis showed that the protein level of MMP-9 in right atrial myocardia was positively correlated with right atrial area (r =0.73, P<0.05) and the protein level of TIMP-1 had a positive correlation with right atrial pressure (r =0.81, P<0.05) . Ang II in right atrial myocardia was positively correlated with the content of collagen and the protein expression level of MMP-9 (r=0.86, P<0.01; r =0.82, P<0.05, respectively), and the calcium concentration of right atrial myocardia was positively correlated with the protein expression level of MMP-9 0=0.72, P<0.05) .Conclusions: (1) Atrial fibrillation models of right atrial rapid pacing caused right atrial structural remodeling, which referred to right atrial myocardial ultrastructural changes, right atrial interstitial fibrosis, enlargement of right atrium and alterations of right atrial functions. (2) Intracelluler calcium overload might result in the changes of the ultrastrutures in right atrial myocardial cells. (3) The activation of renin-angiotensin system was an crucial mechanism responsible for the extracellular matrix fibrosis of right atrium. (4) The imbalance of MMP-9/TIMP-1 system was an important molecular mechanism of the enlargement of right atrium. (5) Local angiotensin II elevation and calcium overload played important roles in the activations of MMP-9. (6) Angiotensin-converting enzyme inhibitor (ACEI)-captopril could generally inhibit structural remodeling of right atrium in dogs with AF, which included the improvement of right atrial ultrastructures, the alleviation of interstitial fibrosis of right atrium, the reduction of dilated right atrium and the renewal of right atrial functions. (7) The protective effect of captopril on the right atrium in AF dogs was that it could prevent the structural remodeling via inhibiting the activation of MMP-9 by blocking the renin-angiotensin system. (8) Acoustic quantification (AQ) technique supplied a significant method to monitor the dynamic changes of right atrial structures and functions in the process of establishing animal models with AF.