Up-regulation of inositol 1,4,5 trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation

OBJECTIVES: We examined whether patients with atrial fibrillation (AF) have alterations in atrial inositol 1,4,5 trisphosphate receptors (IP3 receptors). BACKGROUND: Abnormal intracellular Ca2+ homeostasis occurs in chronic AF. The intracellular Ca2+ concentration is regulated by ryanodine and IP3 receptors. We recently reported alterations in ryanodine receptors in atrial tissue from patients in chronic AF. METHODS: We analyzed IP3 receptor expression in the right atrial myocardium from 13 patients with mitral valvular disease (MVD) with AF (MVD/AF), five patients with MVD who had normal sinus rhythm (MVD/NSR) and eight control patients with NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on atrial tissue. RESULTS: The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than it was in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above control (0.14 +/- 0.08). The relative expression level of IP3 receptor messenger RNA was significantly greater in the MVD/AF group (0.028 +/- 0.008) than it was in the control group (0.015 +/- 0.004, p < 0.01), but patients with MVD/AF did not differ from patients with MVD/NSR (0.020 +/- 0.006). The relative expression levels of IP3 receptor protein and messenger RNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mm Hg and right atrial pressure > or = 5 mm Hg. Inositol 1,4,5 trisphosphate receptors were over-expressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD. CONCLUSIONS: Since chronic mechanical overload of the atrial myocardium increased IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating or perpetuating AF.     

Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation.

OBJECTIVES: Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca2+ regulatory proteins in the atrial myocardium. BACKGROUND: Clinically, AF is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca2+ homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca2+ abnormalities are an important mediator of sustained AF. METHODS: We measured the maximum number of [3H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca2+-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR). RESULTS: In AF patients, 1) Bmax was significantly lower in each atrium (0.21+/-0.03 pmol/mg [right], 0.16+/-0.04 pmol/mg [left]) than in the right atrium (0.26+/-0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10(-2)+/-1.28 x 10(-2)) and right (1.70 x 10(-2)+/-1.78 x 10(-2)) atrium than in the right atrium of NSR patients (6.11 x 10(-2)+/-2.79 x 10(-2)); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 x 10(-2)+/-4.01 x 10(-2)) and right (7.71 x 10(-2)+/-3.56 x 10(-2)) atrium than in the right atrium (12.60 x 10(-2)+/-3.92 x 10(-2)) of NSR patients. CONCLUSIONS: These results provide the first direct evidence of abnormalities in the Ca2+ regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF.     

Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm

An abnormal distribution of the gap junction occurs in chronic atrial fibrillation (AF). There are conflicting data regarding changes in connexins (Cxs) in experimental models of AF. We examined whether patients with chronic AF have alterations in atrial Cxs. We analyzed the expression of Cx40 and Cx43 in the right atrial myocardium from 10 patients with mitral valvular disease (MVD) who had AF (MVD/AF), 10 patients with MVD who were in normal sinus rhythm (MVD/NSR), and 10 control patients in NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained before surgery, and an electrophysiologic examination was performed during the operation. An immunohistochemical study was performed on atrial tissue. The relative expression level of Cx40 protein was significantly lower in MVD/AF patients (6.5 +/- 4.6) than in either MVD/NSR patients (17.7 +/- 8.9, p <0.05) or controls (24.7 +/- 11.1, p <0.01). The relative expression level of Cx40 messenger ribonucleic acid was also significantly lower in MVD/AF patients (0.23 +/- 0.13) than in MVD/NSR patients (0.47 +/- 0.26, p <0.01) or controls (0.47 +/- 0.17, p <0.01). For Cx43 protein and messenger ribonucleic acid, there was no significant difference in relative expression levels among the 3 groups. Interestingly, the level of serine-phosphorylated Cx40 was approximately 52% greater in MVD/AF patients than in controls. In MVD/AF patients, the immunoreactive signal of Cx40 was significantly lower than in controls. There was no significant difference in the connective tissue-volume fraction among the groups. Thus, downregulation of Cx40 and abnormal phosphorylation of Cx40 may result in abnormal cell-to-cell communication and alteration in the electrophysiologic properties of the atrium, leading to the initiation and/or perpetuation of AF.     

Altered patterns of gene expression in response to chronic atrial fibrillation

To obtain greater insight into atrial remodeling at the molecular level we analyzed the changes in gene expression in human atrial tissue between patients with chronic atrial fibrillation (AF) and those with normal sinus rhythm (NSR). cDNA microarray analysis was used to identify genes differentially expressed during sustained AF of more than 6 months (n = 9, mean age, 45 +/- 12, 6 males and 3 females) as compared to those with NSR (n = 9, mean age, 47 +/- 13, 6 males and 3 females). Western blot analysis was performed to confirm the altered gene expression and to establish the changes in protein expression. DNA gel electrophoresis to establish DNA ladder formation, which was associated with apoptosis in response to chronic AF, was performed. Microscopic findings were observed via electron microscopy. In the microarray analysis, out of 8,167 candidate genes, 66 genes showed a significant change in the expression level in the patients with chronic AF, which was in contrast to those with NSR. Among those, 31 genes were consistently down-regulated and 35 up-regulated more than 2-fold. The relative amounts of the Bcl-2 and p27 in the atrial tissue were decreased and angiotensin II type 2 (AT2) receptor and p21 were increased in the patients with chronic AF as compared to those with NSR. The atrial cardiomyocytes in chronic AF showed a prominent DNA ladder, which is a biochemical hallmark of apoptosis. The expression of Bcl-2, AT2 receptor, p21, and p27 were consistent with a significant role in the apoptosis of cardiac myocytes in the patients with chronic AF.     

The L-type Ca2+-channel subunits alpha1C and beta2 are not downregulated in atrial myocardium of patients with chronic atrial fibrillation

OBJECTIVE: Electrical remodeling as well as atrial contractile dysfunction after the conversion of atrial fibrillation (AF) to sinus rhythm (SR) are mainly caused by a reduction of the inward L-type Ca(2+) current (I(CaL)). We investigated whether the expression of L-type Ca2+-channel subunits was reduced in atrial myocardium of AF patients. METHODS: Right atrial appendages were obtained from patients undergoing coronary artery bypass graft surgery (CAD, n = 35) or mitral valve surgery (MVD, n = 37). Seventeen of the CAD patients and 18 of the MVD patients were in chronic (>3 months) AF, whereas the others were in SR. The protein expression of the L-type Ca2+-channel subunits alpha1C and beta2 was quantified by western blot analysis. Furthermore, we measured the density of dihydropyridine (DHP)-binding sites of the L-type Ca2+ channel using 3H-PN220-100 as radioligand. RESULTS: Surprisingly, the alpha1C and the beta2-subunit expression was not altered in atrial myocardium of AF patients. Also, the DHP-binding site density was unchanged. CONCLUSION: The protein expression of the L-type Ca2+-channel subunits alpha1C or beta2 is not reduced in atrial myocardium of AF patients. Therefore, the reduced I(CaL) might be due to downregulation of other accessory subunits (alpha2delta), expression of aberrant subunits, changes in channel trafficking or alterations in channel function.     

Inositol-1,4,5-trisphosphate and ryanodine-dependent Ca2+ signaling in a chronic dog model of atrial fibrillation

Ca2+ signaling regulation plays an important role in triggering and/or maintaining atrial fibrillation (AF). Little is known about the relationship of the inositol-1,4,5-triphosphate receptors (InsP3Rs) and ryanodine receptors (RyRs) in left atrium to chronic AF. In this study, we investigated the expression and function of InsP3R1, InsP3R2 and RyR2 in a chronic dog model of AF. AF was induced in 6 dogs by rapid right atrial pacing for 24 weeks, and a sham procedure was performed in 5 dogs (control group). The intact left atrial myocytes were used to examine the expression and function of InsP3Rs, RyRs by BODIPY(O,R) TR-X ryanodine, heparin-fluorescein conjugate, and were stimulated by caffeine, ATP to release Ca2+ through RyRs, InsP3Rs separately. We also assessed the molecular components of left atrial tissue underlying the amount of RyR2, InsP3R1 and InsP3R2 determined by RT-PCR, immunohistochemistry and Western blot analysis. In the chronic AF group, the Ca2+ released through RyRs is not altered, but the Ca2+ released through InsP3Rs increased significantly. RyR2 distributed in cytosol of myocytes, cellular membrane; its expression significantly decreased in AF group compared to controls. InsP3R1 distributed in cytosol, InsP3R2 distributed not only in cytosol, cellular membrane, but also in nuclear envelope and intercalated discs. The InsP3R1 and InsP3R2 expression significantly increased in chronic AF group compared to controls. These results indicated that in a chronic dog model of AF, the expression and function of RyR2 down-regulated; on the contrary, the expression and function of InsP3R1, InsP3R2 up-regulated, and InsP3R2 may be the major InsP3Rs, which regulate intracellular or even intercellular Ca2+ signal transmission.     

慢性心房颤动患者心房肌浆网钙离子ATP酶及罗纳丹受体mRNA表达变化的研究

研究慢性心房颤动 (简称房颤 )患者Ca2 + 调节蛋白 肌浆网Ca2 + ATP酶及罗纳丹受体 (RyR)mRNA表达的改变 ,探讨房颤时心房肌细胞钙超载的原因及其在房颤发生和维持中的作用。选择 2 0例风湿性心脏病 (以二尖瓣狭窄为主 )接受瓣膜置换术者 ,于术中插管前取右心耳组织约 10 0mg ,采用逆转录 聚合酶链式反应技术 ,测定肌浆网Ca2 + ATP酶及RyR2 mRNA的变化。结果 :房颤者肌浆网Ca2 + ATP酶及RyR2 mRNA水平较窦性心律者明显下调 (分别为 0 .85 4± 0 .2 0 7vs 1.832± 0 .379,P <0 .0 0 1;1.4 12± 0 .319vs 2 .2 5 0± 0 .4 6 8,P <0 .0 5 ) ,且与临床血流动力学参数及性别、年龄无显著相关性。结论 :房颤患者肌浆网Ca2 + ATP酶及RyR2 mRNA表达水平下调 ,表明心房肌浆网钙离子调节蛋白可能参与房颤的发生或维持     

风湿性心脏病慢性心房颤动患者钙转运调控蛋白和钙激活中性蛋白酶基因转录的表达改变

目的测定心房肌钙转运调控蛋白和钙激活中性蛋白酶(calpain1)的mRNA表达,探讨风湿性心脏瓣膜病(风心病)心房颤动(房颤)患者心房肌电重构和结构重构以及心功能下降的分子生物学机制及其在房颤发生、维持中的作用。方法采集风心病窦性心律组患者12例和房颤组患者16例的右心耳组织,应用半定量逆转录-聚合酶链反应(RT-PCR)方法,测定心房肌钙转运调控蛋白和calpain1的mRNA表达水平。结果与窦性心律组相比,房颤组L-型电压依赖钙通道a1c亚基(LVDCCa1c)、肌浆网Ca2+-ATP酶、兰尼碱受体(RYR2)的mRNA表达水平明显下调(均为P<0.01),三磷酸肌醇受体(IP3R1)的mRNA表达水平上调(P<0.05),房颤组心房肌calpain1的mRNA表达水平上调(P<0.05),且与LVDCCa1c的mRNA表达呈负相关(r=-0.583,P<0.05)。结论房颤患者心房肌钙转运调控蛋白和calpain1转录水平调控失衡可能是心房肌电重构和结构重构以及心功能下降的分子生物学机制之一,与房颤的发生和维持有关。     

Left atrial appendage function and abnormal hypercoagulability in patients with atrial flutter

STUDY OBJECTIVES: The prevalence of thromboembolism might be higher than previously recognized in patients with atrial flutter (AFL) based on findings of transesophageal echocardiography (TEE). To evaluate the potential prothrombotic state in patients with AFL, TEE findings and hemostatic markers were compared among patient groups with AFL, normal sinus rhythm (NSR) and chronic nonvalvular atrial fibrillation (AF). DESIGN AND SETTINGS: Cross-sectional study at a university hospital. METHODS: In 28 patients (mean age, 63 years) with AFL, 58 patients (mean age, 66 years) with AF, and 27 patients (mean age, 61 years) with NSR who underwent TEE, plasma levels of markers for platelet activity (platelet factor 4 and beta-thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex and prothrombin fragments 1 and 2) and fibrinolytic status (d-dimer and plasmin-alpha(2)-plasmin inhibitor complex) were determined. RESULTS: Left atrial appendage (LAA) blood flow velocity in patients with AFL was higher (p < 0.05) than that in patients with AF, but was lower (p < 0.05) than that in patients with NSR (AF, 25 +/- 2; AFL, 44 +/- 4; NSR, 60 +/- 4 cm/s). Dense left atrial spontaneous echo contrast (SEC) was found in 4 patients (14%) with AFL and 16 patients (28%) with AF. There was no significant difference in plasma levels of hemostatic markers between the AFL group and the NSR group. AFL patients with impaired LAA function (LAA flow < 30cm/s, dense SEC, or both), however, showed higher level of d-dimer and beta-TG than those without impaired LAA function (d-dimer, 1.9 +/- 0.6 microg/mL vs 0.4 +/- 0.1 microg/mL; beta-TG, 73 +/- 17 ng/mL vs 33 +/- 5 ng/mL, p < 0.05). CONCLUSIONS: Patients with AFL as a whole are not in the prothrombotic state as compared with those with AF. However, patients with AFL and impaired LAA function are at potentially high risk for thromboembolism and might require anticoagulation.     

持续性心房颤动患者心房肌细胞L型钙通道电流变化的研究

目的比较窦性心律(窦律)患者和持续性心房颤动(房颤)患者心房肌细胞L-型钙通道电流密度及通道电压依赖的激活和失活特性变化。方法应用两步酶解法获得单个人体心房肌细胞,采用常规全细胞膜片钳技术记录L-型钙通道电流,观察18例窦律患者和12例持续房颤患者右心房肌L-型钙通道电流密度及动力学特性变化。结果(1)持续房颤组与窦律组相比,L-型钙通道电流密度降低,测试脉冲从-40~0mV时的L-型钙通道电流密度分别为(-4.58±0.39)pA/pF(n=21)和(-1.32±0.19)pA/pF(n=12),两组比较P<0.01。(2)动力学特性:窦律组与持续房颤组比较,通道激活曲线参数半数最大激活电压(V1/2)、斜率因子(K)以及失活曲线参数半数最大失活电压(V1/2)、斜率因子(K)差异均无统计学意义。结论持续房颤患者心房肌细胞L-型钙通道电流密度明显降低,其通道动力学特性变化差异无统计学意义。L-型钙通道电流密度的变化是房颤时“心房电生理重构”离子机制之一。     

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort.

OBJECTIVE: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. METHODS: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca(2+) and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca(2+)-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na(+)/Ca(2+)-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. RESULTS: In 72 muscle preparations of SR patients contractile force was 10.9+/-1.8 mN/mm(2) compared to 3.3+/-0.9 mN/mm(2) (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na(+)/Ca(2+)-exchanger was upregulated by 67% in atria of AF patients. CONCLUSIONS: AF-induced atrial contractile dysfunction is not due to beta-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca(2+)-channel and an increased Ca(2+) extrusion via the Na(+)/Ca(2+)-exchanger seem to be responsible for the depressed contractility in remodeled atria.     

心房颤动患者心房肌浆网ryanodine受体、1,4,5-三磷酸肌醇受体mRNA表达变化的研究

目的：研究心房颤动（房颤）患者肌浆网钙释放通道：ranodine受体（ryanodine receptor type2,RyR2)及1，4，5－三磷酸肌醇受体（1，4，5－trisphosphate rinositol receptor,IP3R1)mRNA表达的改变，探讨房颤时心肌细胞浆Ca^2 超负荷的原因，方法：38例风湿性心脏病二尖瓣狭窄接受外科手术者，手术时取右心房及右心耳各约100mg,通过逆转录－聚合酶链反应技术，以GAPDH为内参照，测量RyR2及IP3R1mRNA的变化，结果：房颤患者肌浆网RyR2和IP3R1mRNA较窦性心律者上调，心房不同部位无差别，地高辛，卡托普利，美托洛尔等药物对RyR2和IP3R1mRNA水平表达无明显影响，结论：房颤患者RyR2和IP3R1上调，说明心肌细胞浆Ca^2 超负荷与肌浆网钙库的释放增加有关。     

Effects of ryanodine receptors block on spontaneous initiation of atrial fibrillation in the intact canine heart

To study the possible role of intracellular Ca2+ overload in initiation of cholinergic-dependent atrial fibrillation (AF), we tested the effects of ryanodine in canine models of AF. In anesthetized open-chest dogs (n=10) AF was induced by two methods: (I) perfusion (9 ml/min) with normal Tyrode solution containing acetylcholine (ACh) into the sinus node artery (SNA) and (II) stimulation of the right vagal nerve (VS, 5 sec train). AF was induced in all dogs: by perfusion with ACh (3.7-/+1.5 mcM) into the SNA in 97-/+3% of attempts and by VS in 78-/+6% of attempts. Intravenous infusion of ryanodine (5 mg/kg) did not prevent induction of AF during ACh perfusion (84-/+5%, NS) but completely prevented the induction of AF by VS (4-/+3%, p<0.001). Atrial activation mapping (112 unipolar electrodes) did not show any significant differences between the beginning of ACh-dependent AF in control and after ryanodine treatment. Ryanodine significantly reduced both systolic and diastolic arterial pressures but had no effect on heart rate, atrial effective refractory period (AERP) and conduction velocity for one hour after infusion. Ryanodine, itself, did not exert antivagal activity, so after ryanodine treatment in the presence of VS (8 Hz) the reduction of AERP and the deceleration of heart rate were similar to that in control. These data suggest that ryanodine can suppress the initiation of AF induced by VS but not AF induced by ACh perfusion. We can conclude that the initiation of AF during ACh perfusion unlikely relates to triggering activity induced by intracellular Ca2+ overload. In addition, we suggest that besides ACh some 'unclear' ryanodine sensitive factor(s) contribute to the initiation of AF induced by VS.     

Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease

TIVES: We postulated a change of angiotensin II receptor subtype expression in patients with lone atrial fibrillation (AF) and AF with underlying mitral valve disease (MVD) both compared with sinus rhythm (SR). BACKGROUND: Atrial fibrillation is a progressive disease associated with electrical and structural remodeling. Angiotensin II (ANGII) is involved in the process of myocardial remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2 (AT(1) and AT(2)). METHODS: Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with or without underlying MVD. The AT(1) and AT(2) protein levels were measured by quantitative Western blotting techniques. RESULTS: The AT(1) protein level in the LA was significantly increased in patients with AF (all forms) compared with SR (p < 0.05), whereas AT(2) expression was not significantly altered. Comparison of the subgroups revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or without MVD. Additionally, investigations of ANGII receptor subtypes in the RA did not exhibit any significant changes either in AT(1) or in AT(2) in patients with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor subtype expression in LA. CONCLUSIONS: Atrial fibrillation is associated with an up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the AT(2) expression in the atrium. Because we found an enhanced expression of AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of AF in the LA.     

Linear lesions provide protection from atrial fibrillation induction with rapid atrial pacing

INTRODUCTION: In the animal model, segmentation of the atria with radiofrequency-generated linear lesions (LL) using the loop catheter has been shown to be highly effective in terminating chronic atrial fibrillation (AF). This study addresses the question whether the same lesion set also would prevent reinduction and sustainability of AF. METHODS AND RESULTS: We studied two groups of dogs. The AF group included eight dogs in which the atria were paced until chronic AF was present. After 6 months of sustained AF, the dogs were converted to normal sinus rhythm (NSR) by the creation of LL in both atria. Rapid atrial pacing was restarted 6 months later and continued for 4 weeks. In the NSR group, there were nine dogs in NSR without inducible AF at baseline. LL were created, and after 6 months rapid atrial pacing was applied for 4 weeks. Rhythm status was monitored weekly. Transthoracic echocardiography was performed at baseline, before linear lesion placement, and before pacing/repacing. At the conclusion of the study, the hearts were excised and examined. The lesions were stained, and their quality was assessed. AF was induced in a much shorter interval in the dogs in which AF had previously been present than in NSR dogs (8 +/- 5 days vs 25 +/- 13 days; P < 0.05). LL prevented sustainability of AF induced via rapid pacing once the pacing stimulus was stopped. Incomplete lesions were associated with increased inducibility of atrial tachycardia and AF. CONCLUSION: In this animal model of AF, LL are not only capable of terminating chronic AF, but also lead to self-termination of AF once the rapid pacing is stopped. Self-termination of AF after induction with rapid pacing was not observed in this AF model in the absence of LL. In the dogs with 6 months of AF, the presence of AF led to increased atrial susceptibility to AF induction by rapid pacing, even with LL and after 6 months of recovery. Incomplete LL allows induction of atrial tachycardia and AF.     

M2 and M3-muscarinic acetylcholine receptors remodelling in patients with a dilated atrium

BACKGROUND: Studies have shown that autonomic tone plays an important role in the pathogenesis of atrial fibrillation (AF) and remodelling of I(K, ACh) in chronic AF serves as a compensatory mechanism for the AF. The relation between atrial size and AF has been established. We investigated the remodelling of muscarinic receptors in patients with dilated atrium and assessed the relationship between the muscarinic receptor remodelling and the dilated atrium. METHODS: A small piece of the tip of the right atrial appendage was obtained from 19 patients in sinus rhythm (SR), 28 patients with mitral stenosis and 10 patients with chronic AF (AF > 6 months). Western-blot was used to determine the expression of M2 and M3 receptors. RESULTS: Patients with mitral stenosis and chronic AF had a larger left atrial diameter than patients in SR. The densities of the M2 receptor in patients with mitral stenosis (with AF and with SR) and chronic AF were lower than that in patients with SR (0.54 +/- 0.08 vs. 0.29 +/- 0.06, 0.26 +/- 0.05 and 0.28 +/- 0.06, P < 0.05). However, the densities of the M3 receptor in patients with mitral stenosis and chronic AF were higher than that in patients with SR (0.07 +/- 0.01 vs. 0.18 +/- 0.02, 0.17 +/- 0.01 and 0.15 +/- 0.01, P< 0.05). Furthermore, there was no significant difference in M2 and M3 receptors between AF and SR in patients with mitral stenosis. CONCLUSION: Remodelling of M2 and M3 receptors is not associated with AF, but with the dilated left atrium.     

Haemodynamics of induced atrial fibrillation: a comparative assessment with sinus rhythm, atrial and ventricular pacing

The haemodynamics and myocardial lactate consumption during induced atrial fibrillation (AF) were studied in 10 patients with paroxysmal AF. Their mean age (+/- SD) was 61 +/- 5 years and none had clinical evidence of ischaemic or rheumatic heart disease. Compared with sinus rhythm, the onset of AF was associated with a reduction in systolic blood pressure (152 +/- 13 mmHg) in AF vs 169 +/- 23 mmHg in sinus rhythm, P less than 0.01). There was no consistent change in cardiac output at the onset of AF compared with sinus rhythm, but the cardiac output was lower compared with regular atrial pacing at rates similar to those of induced AF (3.85 +/- 0.76 vs 4.38 +/- 0.89 l min-1, P less than 0.02). Compared with sinus rhythm or rate-matched atrial pacing, AF was associated with an elevated pulmonary arterial pressure (24.2 +/- 5.6 mmHg in AF vs 17.9 +/- 14.4 mmHg in sinus rhythm, P less than 0.01) and pulmonary arterial wedge pressure (18.6 +/- 5.6 vs 9.7 +/- 3.9 mmHg, P less than 0.01). The haemodynamic changes during AF were similar to those seen during regular ventricular pacing at an equivalent rate, although the latter was associated with a lower systolic blood pressure (152 +/- 13 mmHg in AF vs 136 +/- 25 mmHg in ventricular pacing, P less than 0.05) and higher right atrial pressure (8.2 +/- 4.4 vs 11.5 +/- 7.5 mmHg respectively, P less than 0.05), presumably due to the deleterious effects of cannon 'a' waves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased inflammatory cell infiltration in the atrial myocardium of patients with atrial fibrillation

Atrial fibrillation (AF) may be caused by structural and electrophysiological changes in the atria induced by inflammation. This study analyzed 35 adult patients with symptomatic severe mitral valve disease and moderate-to-severe tricuspid valve disease and without coronary artery disease who underwent valve operations for congestive heart failure; 18 patients had persistent AF and 17 patients had no history or electrocardiogram examination of AF before surgery. Atrial appendageal tissues obtained during surgery were evaluated for histopathological changes. The number of inflammatory cells identified as CD45-positive cells in the right atrial myocardium in the AF group (7.5 +/- 7.5 cells per high power field) was significantly higher than that of normal controls (2.7 +/- 1.5 cells per high power field, p = 0.0018). The number of inflammatory cells in the right atrial myocardium did not differ between the sinus group and normal controls (2.7 +/- 1.5 vs 2.6 +/- 2.2 cells per high power field, p >0.05). Additionally, the number of inflammatory cells in the atrial myocardium did not differ between the right and left atria in patients with AF (7.5 +/- 7.5 cells per high power field for right atria vs 7.1 +/- 4.2 cells per high power field for left atria, p = 0.7563). Moreover, correlation analysis revealed a significant association between the number of inflammatory cells in the right atrial myocardium and the number of inflammatory cells in the left atrial myocardium in patients with AF (r = 0.6145, p = 0.0067). In conclusion, inflammatory cell infiltration increases in the atrial myocardium of patients with AF.