贝那普利联用胺碘酮预防心房颤动复发改善左心房功能临床研究

目的:观察贝那普利在持续性心房颤动复律后维持窦性心律中的作用及其对左心房收缩功能的影响.方法:80例持续性心房颤动(持续超过7日)患者,药物或电复律后随机分为两组,Ⅰ组40例给予胺碘酮0.2 g每日1次;Ⅱ组40例给予贝那普利10 mg每日1次,胺碘酮0.2 g,每日1次;两组均连服6个月.分别于治疗后第1周、2周、1个月、2个月、4个月及6个月复查心电图或动态心电图,观察心房颤动复发情况;复律后次日及6个月后做UCG检查,观察左心房功能变化.结果:共71例完成治疗.随访6个月,心房颤动复发Ⅰ组34%(12/35),Ⅱ组为14%(5/36),两组比较差异有统计学意义(P＜0.05),Ⅱ组复律后次日及治疗6个月后,超声测量左心房内径由(43±12)mm缩小为(35±11)mm,治疗前与治疗6个月后比较差异有统计学意义(P＜0.01),而Ⅰ组上述指标比较差异无统计学意义(P＞0.05).结论:贝那普利加胺碘酮用于持续性心房颤动复律后维持窦性心律,较单用胺碘酮更有效,长期服用贝那普利可逆转左心房扩大,降低左心房压,有利于消除心房颤动复发的基础.     

Mechanisms of termination and prevention of atrial fibrillation by drug therapy

Atrial fibrillation (AF) is a disorder of the rhythm of electrical activation of the cardiac atria. It is the most common cardiac arrhythmia, has multiple aetiologies, and increases the risk of death from stroke. Pharmacological therapy is the mainstay of treatment for AF, but currently available anti-arrhythmic drugs have limited efficacy and safety. An improved understanding of how anti-arrhythmic drugs affect the electrophysiological mechanisms of AF initiation and maintenance, in the setting of the different cardiac diseases that predispose to AF, is therefore required. A variety of animal models of AF has been developed, to represent and control the pathophysiological causes and risk factors of AF, and to permit the measurement of detailed and invasive parameters relating to the associated electrophysiological mechanisms of AF. The purpose of this review is to examine, consolidate and compare available relevant data on in-vivo electrophysiological mechanisms of AF suppression by currently approved and investigational anti-arrhythmic drugs in such models. These include the Vaughan Williams class I-IV drugs, namely Na⁺ channel blockers, β-adrenoceptor antagonists, action potential prolonging drugs, and Ca²⁺ channel blockers; the “upstream therapies”, e.g., angiotensin converting enzyme inhibitors, statins and fish oils; and a variety of investigational drugs such as “atrial-selective” multiple ion channel blockers, gap junction-enhancers, and intracellular Ca²⁺-handling modulators. It is hoped that this will help to clarify the main electrophysiological mechanisms of action of different and related drug types in different disease settings, and the likely clinical significance and potential future exploitation of such mechanisms.     

Spectral analysis of chronic atrial fibrillation and its relation to minimal defibrillation energy

The average rate of fibrillatory activity may reflect the global activation pattern of AF. Electrical cardioversion is the most effective method of converting chronic AF to sinus rhythm. The aim of this study was to investigate the relation between the minimal defibrillation energy requirement and the dominant frequency of chronic AF. Twenty-nine patients with chronic AF (mean duration 57.9 +/- 7.7 months) underwent external electrical cardioversion. Before cardioversion, the frequency content of the 60-second AF in ECG lead V1 was quantified using digital signal processing. After band-pass filtering, QRST complexes were cancelled using a recursive lease squares algorithm. The resulting fibrillatory baseline signal was subjected to fast Fourier transform and was displayed as a power spectrum. The dominant AF frequency was found to range from 4.9 to 8.7 Hz (mean 6.7 +/- 0.9 Hz). Twenty-six patients had successful conversion of AF to sinus rhythm without immediate recurrence. There was a positive correlation between the minimal defibrillation energy and the dominant frequency of chronic AF (rho = 0.414, P = 0.035). Thus, power spectral analysis of AF using the surface ECG is feasible and may be useful in predicting the minimal shock energy required for successful cardioversion of chronic AF.     

Immunopathogenesis and biomarkers of recurrent atrial fibrillation following ablation therapy in patients with preexisting atrial fibrillation

Introduction: Recurrent atrial fibrillation (RAF) following ablation therapy occurs in about 50% of patients. The pathogenesis of RAF is unknown, but is believed to be driven by atrial remodeling in the setting of background inflammation. Structural, electrophysiological and mechanical remodeling has been associated with atrial fibrillation (AF). Inflammation and fibrotic remodeling are the major factors perpetuating AF, as mediators released from the atrial tissues and cardiomyocytes due to mechanical and surgical injury could initiate the inflammatory process. In this article, we have critically reviewed the key mediators that may serve as potential biomarkers to predict RAF.

Areas covered: Damage associated molecular patterns, heat shock proteins, inflammatory cytokines, non-inflammatory markers, markers of inflammatory cell activity, and markers of collagen deposition and metabolism are evaluated as potential biomarkers with molecular treatment options in RAF.

Expert commentary: Establishing biomarkers to predict RAF could be useful in reducing morbidity and mortality. Investigations into the role of DAMPs participating in a sterile immune response may provide greater insight into the pathogenesis of RAF. Markers evaluating immune cell activity, collagen deposition, and levels of heat shock proteins show the greatest promise as potential biomarkers to predict RAF and develop novel therapies.     

慢性心房颤动的治疗

慢性心房颤动(房颤)的治疗主要是针对其快速心率和卒中/栓塞潜在危险,包括心率控制、抗栓治疗和尝试恢复窦性心律。虽然导管消融术可使部分慢性房颤患者恢复窦性心律,但是尚缺乏足够临床证据准确评价其疗效。因此,对于大部分慢性房颤患者,应严格遵循房颤治疗指南建议,积极控制心率,加强抗血栓治疗。     

Action potential remodeling in the human right atrium with chronic lone atrial fibrillation

It has been shown in animal experiments that recurrent induction of atrial fibrillation (AF) or long-lasting atrial pacing causes a shortening of the atrial effective refractory period (ERP) and action potential duration (APD) and a loss of their physiological adaptation to rate. Much remains to be clarified as to the electrical remodeling in human patients with chronic AF. We recorded monophasic action potentials (MAPs) from the right atrium at pacing cycle lengths (CLs) of 300, 333, 400, 500, 600, and 750 ms after external cardioversion in 13 patients with chronic lone AF. Their configuration was compared with those obtained from 13 control patients. APDs at 50% and 90% repolarization (APD50, APD90) at the shortest CL (300 ms) in control and AF patients were 131 +/- 14, 211 +/- 19 ms and 136 +/- 12, 210 +/- 22 ms, respectively (mean +/- SD). APDs in control patients increased linearly with increases of CL, reaching maximal values of 174 +/- 30 ms (APD50) and 277 +/- 38 ms (APD90) at a CL of 750 ms. In AF patients, the steady-state CL-APD relation was shifted downward and flattened at CLs > 500 ms; APD50 and APD90 at a CL of 750 ms were 158 +/- 19 ms, 232 +/- 28 ms, respectively. APD90s at CLs of 600 and 750 ms were significantly shorter in AF than in control patients. No statistically significant difference was obtained in APD50 between the two groups at any CL tested. MAP configuration in AF patients was characterized by an acceleration of the late repolarization. The difference between APD90 and APD50 (APD90-50) in control patients was increased with increases of CL, reaching a plateau at a CL of 600 ms. This CL dependent slowing of the late repolarization of MAPs was abolished in AF patients. The atrial ERP, measured at CLs of 400 and 600 ms, showed changes parallel to those of APD90. ERP at a CL of 600 ms in AF patients (224 +/- 13 ms) was significantly shorter than that in control patients (247 +/- 25 ms). We conclude that chronic lone AF leads to electrical remodeling in the human atrium, which causes a loss of rate response of the late repolarization of action potential, leading to a shortening of APD and ERP at slower heart rates.     

Effect of IKr blocker nifekalant on atrial action potential duration after successful internal cardioversion of chronic atrial fibrillation

BACKGROUND: Chronic atrial fibrillation (AF) is characterized by a marked decrease in the atrial effective refractory period (ERP) and in the ERP adaptation to rate as well as a decrease in the atrial conduction velocity. Little information is available about the ionic mechanisms underlying AF in humans. MATERIALS AND METHODS: We studied the effect of IKr blocker nifekalant on the rate-dependent changes in atrial action potential duration in 11 patients after successful internal cardioversion of chronic AF of >2 months duration and in 7 patients without AF. In AF patients, right atrial (RA) monophasic action potential (MAP) was recorded at pacing cycle lengths (CLs) of 800-250 ms before and after administration of nifekalant. In control patients, RAMAP was recorded at CLs of 600 and 350 ms before and after administration of nifekalant. RESULTS: Nifekalant significantly increased RAMAPD at 90% repolarization (RAMAPD90) at CLs of 800-300 ms in the AF patients. The increase in RAMAPD90 by nifekalant became significantly smaller at shorter CLs (42.5 +/- 12.4 ms at a CL of 600 ms vs 32.8 +/- 14.5 ms at a CL of 350 ms, P < 0.05). Effect of nifekalant on RAPMAPD was attenuated at CL of 600 ms in AF patients in comparison to control patients (increase in RAMAPD in control; 73.0 +/- 36.6 ms vs increase in RAMAPD in AF; 42.5 +/- 12.4 ms, P < 0.05); however, it was similar at a CL of 350 ms between control and AF patients. CONCLUSIONS: Electrophysiological effects of nifekalant are significantly attenuated in the chronically remodeled human atrium at slower heart rates, but the beneficial effect of RAMAPD prolongation by IKr blocker was well-preserved even at shorter CLs after chronic AF.     

男性心房颤动类型对血浆脑钠肽水平的影响

目的 探讨各类型男性心房颤动与血浆脑钠肽含量的关系.方法 选择入院男性心房颤动患者58例,其中阵发性心房颤动35例(阵发性心房颤动组),持续性心房颤动14例(持续性心房颤动组),永久性心房颤动9例(永久性心房颤动组),于入院后24 h内完成超声心动图和(或)心电图检查,清晨安静平卧状态留取静脉血,采用放射免疫法检测脑钠肽含量.结果 男性永久性心房颤动组血浆脑钠肽平均水平[(2343.25±820.24)μg/L]]显著高于持续性心房颤动组[(576.43±223.07)μg/L]及阵发性心房颤动组[(632.74±103.93)μg/L],差异有统计学意义(t值分别为8.74,8.73,P均＜0.001),持续性心房颤动组与阵发性心房颤动组血浆脑钠肽水平差异无统计学意义(t值为0.59,P＞0.05).结论 脑钠肽不仅是反映早期心功能受损的敏感指标,而且与心房颤动有较密切的关系,尤其在永久性心房颤动患者明显升高.

Abstract：

Objective To explore the effect of different type of atrial fibrillation(AF) on plasma brain natriuretic peptide(BNP) level in male patients.Methods Fifty-eight hospitalized male patients with AF were enrolled,including 35 cases with paroxysmal AF,14 cases with persistent AF,and 9 cases with permanent AF.All subjects had the examination of echocardiography/electrocardiogram within 24 h after admission.Venous blood sample were collected in a quiet prostration state on the next early morning for BNP detection.The plasma BNP level was determined by radioimmunology-assay(RIA).Results The average level of plasma BNP in male patients with permanent AF(2343.25 ± 820.24)μg/L was significantly higher than those with persistent AF([576.43 ± 223.07]μg/L,t=8.74,P＜0.001) and paroxysmal AF([632.74 ± 103.93]μg/L,t=8.73,P＜0.001),but there was no significant difference between the last two groups(t=0.59,P＞0.05).Conclusion BNP is a sensitive indicator of early heart function impairment related with AF,particularly elevates in male patients with permanent AF.     

Evidence for electrical remodelling of the atrial myocardium in patients with atrial fibrillation. A study using the monophasic action potential recording technique

Experimental studies have shown that remodelling of the atrial myocardium is linked to the occurrence and perpetuation of atrial fibrillation (AF). Clinical evidence, however, is insufficient. We recorded monophasic action potentials (MAP) during AF from one to three sites in the right atrium in seven patients with chronic AF (CAF) and in 11 patients with paroxysmal AF (PAF). The fibrillatory (FF) interval between two consecutive upstrokes of the MAP was measured using a computer-assisted manual method. The mean, median, 15th, 10th, 5th percentile and shortest FF intervals were calculated in each patient and used as estimates of the local atrial effective refractory period (AERP) during AF. In three patients burst pacing at 400 and 500 beats min(-1) was delivered during the MAP recording. In nine patients, the AERP was also tested using the extra stimulus technique during sinus rhythm. RESULTS: Thirty-eight recordings were obtained. The shortest FF interval was significantly shorter in patients with CAF as compared with that in patients with PAF (50+/-13 vs. 72+/-31 ms, P<005). Similar differences were seen in the mean, median, 15th, 10th, and 5th percentile FF interval. The AERP during sinusrhythm was significantly longer than the estimated AERPs (P<0 05 to P<0.01) in the nine patients. There was no significant difference in FF interval before and after the burst pacing in the three patients. CONCLUSION: The AERP was significantly shortened during AF, as compared with that during sinus rhythm, and the AERP shortening was more marked in patients with CAF than in patients with PAF. These clinical findings support the connection between the electrical remodelling and the occurrence and/ or perpetuation of the AF.     

心房颤动患者血清和组织miR-223及MMP-9的表达及临床价值

目的探索miRNA-223在房颤患者心房肌组织和血清的表达差异及miRNA-223与MMP-9在房颤患者的表达水平及在房颤结构重构的发生机制。方法患有风湿性心瓣膜病接受心脏瓣膜置换术的患者31例,其中窦性心律患者15例,慢性房颤患者16例。另选取15名健康人血清作为对照组。实时荧光定量PCR检测心房肌组织和血清miRNA-223的相对表达量。ELISA及免疫组织化学检测MMP-9蛋白的表达及分布水平;HE染色及Masson染色观察心肌组织病理结构及胶原纤维含量。结果与窦性心律组相比,房颤组心房肌组织miRNA-223和血清miRNA-223表达水平均显著升高（0.0603±0.0228 vs.0.0261±0.0035,P〈0.01;4.2281±0.9165 vs 2.7613±1.2166,P〈0.05）;房颤组血清MMP-9表达水平高于窦性心律组（4.2281±0.9165 vs 2.7613±1.2166,P〈0.05）;MiRNA-223表达水平与MMP-9蛋白表达呈正相关（r=0.901,P〈0.05）。结论 MiRNA-223表达增高及正向调控MMP-9的表达,共同影响心肌胶原的代谢,促进心肌纤维化,参与房颤发生与维持。miRNA-223有望成为一种新型风湿性心脏病合并房颤的诊断标志物。     

Relation between history of paroxysmal atrial fibrillation and electrophysiological abnormalities of atrial muscle

Although electrophysiological abnormalities of atrial muscle have been evaluated in patients with paroxysmal atrial fibrillation (PAF), no prior study has determined the contribution of the patient's history of PAF to electrophysiological abnormalities. The study population consisted of 108 patients (71 men; mean age, 57 ± 14 years) with symptomatic and idiopathic PAF who underwent electrophysiological study. Before electrophysiological study, histories of frequency, number of PAF episodes per month, and duration, a time interval from the first episode of PAF to electrophysiological study, were examined. At electrophysiological study, endocardial electrograms from 12 right atrial sites were recorded during sinus rhythm, and the right atrial effective refractory period was determined. Longest duration of atrial electrograms, maximal number of fragmented deflections, and number of abnormal atrial electrograms recorded at the right atrial sites were significantly greater in the frequent group (> 1 PAF episode per month, n = 57) than in the infrequent group (< 1 PAF episode per month, n = 51) (98 ± 18 ms vs 88 ± 16 ms, P < 0.005; 8.7 ± 2.6 vs 7.5 ± 2.6, P < 0.05; and 2.2 ± 2.2 vs 1.4 ± 1.6, P < 0.05, respectively). Indices of atrial vulnerability were also greater in the frequent group. Duration of PAF history was significantly correlated with longest duration r = 0.52, P < 0.0001), maximal number of fragmented deflections r = 0.51, P < 0.0001), and number of abnormal atrial electrograms r = 0.58, P < 0.0001). More frequent episodes and longer history of PAF significantly increased the electrophysiological abnormalities of the atrial muscle, suggesting that PAF results in gradual electrical remodeling of the atrial muscle.     

慢性心房颤动患者心房肌超声组织定征研究

目的探讨心房颤动(房颤)患者和窦性心律患者心房肌背向散射积分,诊断慢性房颤时心房肌病理性结构改变。方法选择风湿性瓣膜病患者46例,其中房颤组26例,窦性心律组20例。在左房后壁心肌和心包处测量背向散射积分值(IBS)及背向散射积分周期变异幅度(CVIB)。结果两组间年龄和性别构成比差异无统计学意义(P>0.05)。与窦性心律组比较,房颤组左房心肌标化IBS显著增大(P<0.05),而CVIB则显著降低(P<0.05)。结论慢性房颤患者心房肌显著纤维化和心房机械功能的下降是导致IBS值升高和CVIB降低的原因。     

Early recurrence of atrial fibrillation after external cardioversion

Early recurrence of atrial fibrillation (AF) has been reported to occur in a significant number of patients after internal cardioversion. However, information about early recurrence of AF after external cardioversion has never been reported. The present study was conducted to investigate the clinical and electrophysiological characteristics of early recurrence of AF and its role in failure of cardioversion in patients with chronic AF. METHODS AND RESULTS: The study included 50 consecutive patients, age 69+/-9, with a history of chronic AF for more than 3 months duration and electrical cardioversion. They were divided into two groups according to the presence (group 1) or absence (group 2) of early recurrence of AF. There were 13 (26%) patients in group 1 and 37 (74%) patients in group 2. The age, gender, duration of AF, left ventricular function, left atrial dimension, and underlying heart disease were similar between group 1 and 2. Forty-five patients were successfully converted to sinus rhythm with a mean energy of 158+/-57 . Among those who failed to be converted to sinus rhythm, 4 (80%) belonged to group 1 and 1 (20%) belonged to group 2. The early recurrences of AF were initiated with consecutive APDs; but the numbers of APD in the first 30 seconds after cardioversion were similar between group 1 and 2. However, the coupling interval of the second APD was shorter in group 1 than group 2 (188+/-22 vs 324+/-59 ms, P = 0.003). Nine of the 13 early recurrences were prevented by an increase of shock energy (n = 3) or intravenous amiodarone infusion (n = 6). There were no differences in duration of follow-up, recurrence rate, and time interval to recurrence between group 1 and group 2. Early recurrence of AF occurred in 26% of chronic AF patients who underwent external electrical cardioversion and was a major cause of failure in cardioversion. Early recurrence of AF was initiated by APDs with decreasing coupling intervals and could be prevented with an increase of shock energy or amiodarone.     

慢性淋巴细胞白血病bcl-2基因表达与重排的研究

人类恶性肿瘤常伴有非随机性染色体异常,并由于使调控细胞生长的基因表达失控而在肿瘤的发生中发挥十分关键的作用。bcl-2基因由于t(14,18)染色体易位而激活在低恶度的非霍奇金淋巴瘤的发生和演变中的作用已举世公认。类似的重排和非重排引起的bcl-2过度表达也见于慢性淋巴细胞白血病。我们应用免疫组化染色和聚合酶链反应检测了11例慢性淋巴细胞白血病bcl-2基因表达和重排,结果发现所有病例均高度表达Bcl-2蛋白,1例有t(14,18)(q32,q21)染色体易位。结论提示慢性淋巴细胞白血病普遍存在bcl-2基因高表达,bcl-2基因在慢性淋巴细胞白血病的发生和发展中发挥着十分重要的作用。     

氯沙坦联用胺碘酮对预防心房颤动复发及左心房功能影响的研究

目的 观察氯沙坦联用胺碘酮在持续性房颤转复后窦性心律的作用及对左房功能的影响．方法选择持续性房颤患者93例，药物或电复律后随机分2组：对照组予胺碘酮0．2g，1次／d；观察组在服胺碘酮的基础上予血管紧张素受体拮抗剂（氯沙坦）50mg，1次／d，2周后无低血压，第3周加量100mg，1次／d。观察复律后第2天及6、12个月后测定左心房功能变化和房颤复发情况。结果随访1年后，观察组和对照组房颤复发比较有显著性差异（P〈0．05），而左房内径观察组治疗1年后有显著缩小（P〈0．05），对照组上述指标无显著性差异（P〉0．05）。结论氯沙坦联用胺碘酮在持续性房颤转复后维持窦性心律较单用胺碘酮更有效，并可逆转左房扩大。     

银杏叶对缺血性脑损伤后Bcl-2和Bax基因表达的作用

目的：探讨化学预处理对脑缺血后海马组织原癌基因B细胞淋巴瘤-2（Bcl-2）和Bax基因表达的影响。方法：采用Nagasaway与Zea Longa等介绍的线栓阻塞大脑中动脉（MCA）方法制备大鼠脑缺血模型，并用银杏叶制剂术前连续预处理模型大鼠7d。采用逆转录-聚合酶链反应（RT—PCR）方法测定假手术组、模型组和银杏叶预处理组大鼠缺血后6、12、24和48h海马组织中Bcl-2和Bax的mRNA表达变化。结果：行大脑中动脉闭塞（MCAO）后大鼠海马组织Bcl-2和Bax的mRNA均被诱导表达，缺血后不同时间点Bcl-2 mRNA表达量持续升高；而Bax mRNA表达量在脑缺血24h才达到峰值，随后表达量逐渐下降。银杏叶制剂预处理7d后，缺血后6h和24h大鼠海马组织Bcl-2 mRNA表达水平较模型组明显上调，而Bax mRNA表达于缺血后24h明显下调。结论：银杏叶制剂能有效调控缺血脑损伤后海马组织Bcl-2和Bax的基因表达水平，从而在缺血性脑损伤中起到神经保护作用。