快速右心房起搏致犬心房迷走神经重构的研究

目的 通过对快速心房起搏犬的神经相关因子的研究,观察右心房快速起搏48 h是否引起神经重构及其在心房颤动(房颤)中的作用.方法 健康杂种犬12只,随机分为房颤组(6只)和对照组(6只).右心房起搏600次/min、持续48 h.通过一种在发芽轴突生长丘中表达的蛋白质(GAP-43)和乙酰胆碱转移酶(CHAT)来了解心脏神经萌发和迷走神经的重构.结果 在房颤犬的左心房、左心耳、右心房和右心耳,GAP-43和CHAT的神经密度同对照组相比明显增高,差异均有统计学意义(P<0.05).此外,房颤犬的右心房GAP-43和CHAT的神经密度与左心房有明显差异(P<0.05),显微镜下显示每个样点心脏神经不均匀分布.结论 48 h持续起搏犬右心房形成阵发性房颤,可见明显的神经萌发和迷走神经重构且不均一分布.     

Vagal denervation and atrial fibrillation inducibility: Epicardial fat pad ablation does not have long-term effects

BACKGROUND: Major epicardial fat pads contain cardiac ganglionated plexi of the autonomic, predominantly vagal nerves. Vagal denervation may improve the success rate of atrial fibrillation (AF) treatment. OBJECTIVES: The purpose of this study was to elucidate the long-term effects of fat pad ablation on the electrophysiologic characteristics of the atrium and AF inducibility. METHODS: Six mongrel dogs were studied. Cervical vagal stimulation was applied to determine effects on the sinus node, AV node, atrial effective refractory period (AERP), and AF inducibility. AERP and AF inducibility were evaluated at both the right atrial and left atrial appendages and at the right atrial and left atrial free walls. Radiofrequency energy was delivered epicardially to the entire areas of two major fat pads: right pulmonary vein fat pad and inferior vena cava-left atrium fat pad. Cervical vagal stimulation then was applied to confirm the acute effects of fat pad ablation. The same evaluation was repeated 4 weeks later. RESULTS: The effects of vagal stimulation on the sinus node, AV node, and AERP were significantly eliminated immediately after fat pad ablation. However, these denervation effects disappeared after 4 weeks. At baseline, AF inducibility was increased by vagal stimulation (right atrial appendage: 72% +/- 31% vs 4.8% +/- 12%; right atrial free wall: 75% +/- 31% vs 0.0% +/- 0.0%; left atrial appendage: 60% +/- 29% vs 0.0% +/- 0.0%; left atrial free wall: 65% +/- 42% vs 0.0% +/- 0.0%). Fat pad ablation significantly reduced this vagal stimulation effect (8.3% +/- 20%, 10% +/- 22%, 17% +/- 29%, and 25% +/- 29%, respectively). However, similar to baseline, AF inducibility was strongly augmented by vagal stimulation 4 weeks after fat pad ablation (96% +/- 10%, 100% +/- 0.0%, 100% +/- 0.0%, and 95% +/- 11%, respectively). CONCLUSION: Radiofrequency fat pad ablation may not achieve long-term suppression of AF induction in this canine model.     

Functional characterization of atrial electrograms in sinus rhythm delineates sites of parasympathetic innervation in patients with paroxysmal atrial fibrillation.

OBJECTIVES: This study sought to characterize left atrial (LA) sinus rhythm electrogram (EGM) patterns and their relationship to parasympathetic responses during atrial fibrillation (AF) ablation. BACKGROUND: The mechanistic basis of fractionated LA EGMs in patients with paroxysmal AF is not well understood. METHODS: We analyzed 1,662 LA ablation sites from 30 patients who underwent catheter ablation for paroxysmal AF. Pre-ablation EGM characteristics (number of deflections, amplitude, and duration) were measured in sinus rhythm. Parasympathetic responses during radiofrequency application (increase of atrial-His interval by > or =10 ms or decrease of sinus rate by > or =20%) were assessed at all sites. We also prospectively studied the effect of adenosine, a pharmacological agent mimicking acetylcholine signaling in myocytes, on LA EGMs. Finally, we performed mathematical simulations of atrial tissue to delineate possible mechanisms of fractionated EGMs in sinus rhythm. RESULTS: A specific pattern of pre-ablation sinus rhythm EGM (deflections > or =4, amplitude > or =0.7 mV, and duration > or =40 ms) was strongly associated with parasympathetic responses (sensitivity 72%, specificity 91%). The sites associated with these responses were found to be located mainly in the posterior wall of the LA. Adenosine administration and mathematical simulation of the effect of acetylcholine were able to reproduce a similar EGM pattern. CONCLUSIONS: Parasympathetic activation during AF ablation is associated with the presence of pre-ablation high-amplitude fractionated EGMs in sinus rhythm. Local acetylcholine release could potentially explain this phenomenon.     

射频消融第三脂肪垫对犬心房电生理参数及心房颤动诱发的影响

目的研究射频消融第三脂肪垫对犬心房电生理参数及心房颤动(房颤)诱发的影响。方法观察12只杂种犬在不同起搏周长下,消融第三脂肪垫前后心房不同部位有效不应期(AERP)、AERP离散度、AERP频率适应性,房颤诱发率及其诱发窗口的变化。结果与消融前相比,消融后心率变化差异无统计学意义(P>0.05)。随着起搏周长变短,AERP明显缩短,且差异具有统计学意义(均为P<0.05)。消融术后高位左心房、低位左心房、左心耳部位AERP明显缩短,高位右心房、低位右心房、右心耳部位AERP明显延长(均为P<0.05)。AERP离散度差异无统计学意义(P>0.05)。消融后不同测量部位的房颤诱发率均降低及房颤诱发窗口增宽。结论消融第三脂肪垫达到部分去迷走神经化,使左心房AERP缩短,同时使房颤诱发率降低及房颤诱发窗口增宽。     

慢性快速心房起搏心房颤动犬内皮型一氧化氮合酶mRNA表达变化的研究

为研究慢性快速心房起搏心房颤动(简称房颤)犬模型中心内膜内皮型一氧化氮合酶(eNOS)mRNA表达的变化,探讨其与心房结构重构、血栓形成的关系。13只健康犬随机分为假手术组和起搏组,应用埋藏式高频率心脏起搏器快速起搏心房(400次 /分) 6周,取左、右心房,左、右心耳及主动脉内膜。通过逆转录 聚合酶链反应 (RT PCR),以β actin为内参照,测定犬心内膜eNOSmRNA表达的变化,同时检测血浆NO代谢产物硝酸盐 (NOx)的含量。结果:正常犬心脏eNOSmRNA表达存在差异,左房、左心耳明显高于右房、右心耳;起搏 6周后左房、左心耳eNOSmRNA表达起搏组明显低于假手术组,而右房、右心耳、主动脉无明显差别,血浆NOx起搏组亦明显低于假手术组。结论:正常犬心脏eNOS基因表达是不平衡的,左房明显高于右房。房颤犬eNOSmRNA表达降低可能是心房结构重构,血栓形成的重要因素之一。     

Autonomic mechanism for complex fractionated atrial electrograms: evidence by fast fourier transform analysis

Introduction: The mechanism(s) underlying complex fractionated atrial electrograms (CFAE) is not well understood. We hypothesized that CFAE may be caused by enhanced activity of the intrinsic cardiac autonomic nervous system.
Methods and Results: In 35 anesthetized dogs, via a right or left thoracotomy, sustained atrial fibrillation was induced by local application of acetylcholine (ACh; 10, 100 mM) to the surface of the atrial appendage (AA) or by injection of ACh (10 mM) into the ganglionated plexi (GP). Fast Fourier transform analysis was performed from recordings at AA, atrial sites near the AA, mid portion of the atrium, atrial sites near the GP, and the pulmonary veins. After AF was induced with ACh either by topical application to the AA or by direct injection into the GP, CFAE exhibited a significant gradient of progressively decreasing dominant frequency and incidence of CFAE (CFAE%) from the GP toward distant sites, while regularity index progressively decreased in the opposite direction. Ablation of GP markedly attenuated CFAE and eliminated these gradients.
Conclusions: These results suggest CFAE may result from activation of the intrinsic cardiac autonomic nervous system in these animal models of sustained AF. Ablation of GP attenuates CFAE and eliminates the DF gradient.     

Differences in organization between acute and chronic atrial fibrillation in dogs

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.     

Differential densities of muscarinic acetylcholine receptor and I(K,ACh) in canine supraventricular tissues and the effect of amiodarone on cholinergic atrial fibrillation and I(K,ACh)

BACKGROUND: Vagal nerve plays an important role in the induction and maintenance of atrial fibrillation (AF). This study investigated the differential densities of M2 receptor and acetylcholine-induced inward rectifier K+ current (I(K,ACh)) in atrial appendage, atrium, pulmonary vein (PV) and super vena cava (SVC) to discuss the role of atrial appendage and PV in cholinergic AF. METHODS AND RESULTS: In 10 dogs, action potential duration was determined at 24 sites during bilateral cervical vagal stimulation and amiodarone administration. AF could be induced at first in right atrial appendage (RAA) and right atrium (RA) without left atrial appendage (LAA) and left atrium (LA). Amiodarone decreased the initiation of AF in vivo. Western blot and patch clamp were used to determine M2 receptor and I(K,ACh) in RAA, LAA, RA, LA, PV and SVC. The densities of M2 receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PV and SVC (21.34 +/- 0.92 vs. 8.24 +/- 0.45 pA/pF, p < 0.05). Furthermore, the densities of the M2 receptor and I(K,ACh) in LAA and RAA were higher than that in LA (21.34 +/- 0.92 vs. 14.17 +/- 0.65 pA/pF, p < 0.05). After amiodarone administration, densities of I(K,ACh) in LA and RA were not different, but densities of I(K,ACh )were also less in atrium than in atrial appendage. CONCLUSIONS: Densities of the M2 receptor and I(K,ACh) are higher in atrial appendage than other sites. Atrial appendage perhaps plays an important role in initiation of cholinergic AF. However, PV and SVC less often play an important role in vagotonic paroxysmal AF. Reduced dispersion of I(K,ACh) is the mechanism for amiodarone to therapy AF.     

Endoscopic fluorescence mapping of the left atrium: A novel experimental approach for high resolution endocardial mapping in the intact heart

BACKGROUND: Despite the availability of several mapping technologies for investigating the electrophysiologic mechanisms of atrial fibrillation (AF), an experimental tool enabling high-resolution mapping of electrical impulses on the endocardial surface of the intact left atrium is lacking. OBJECTIVE: The purpose of this report is to present a new optical mapping approach implementing a steerable cardio-endoscope in isolated hearts. METHODS: The system consists of a direct or side-view endoscope coupled to a 532-nm excitation laser for illumination and a CCD camera for imaging of potentiometric dye fluorescence (di-4-ANEPPS, 80 x 80 pixels, 200-800 frames/s). The cardio-endoscope was aimed successively at diverse posterior left atrial locations to obtain high-resolution movies of electrical wave propagation and detailed endocardial anatomic features in the presence and absence of atrial stretch. RESULTS: We present several examples of high-resolution endoscopic posterior left atrial recordings of wave propagation patterns during both sinus rhythm and AF with signal-to-noise ratio similar to conventional optical mapping systems. We demonstrate the endoscope's ability to visualize highly organized AF sources (rotors) at specific locations on the posterior left atrium and posterior left atrium-pulmonary vein junctions. We present video images of waves emanating from such sources as they propagate into pectinate muscles in the left atrial appendage. In particular, we demonstrate this approach is ideally suited for studying the effects of atrial stretch on AF dynamics. CONCLUSION: In isolated hearts, cardio-endoscopic optical mapping of electrical activity should enable comprehensive evaluation of AF activity in the posterior left atrium, the role of local anatomy on AF dynamics, and the efficacy of pharmacologic and ablative interventions.     

不同浓度乙酰甲胆碱介导犬心房颤动的电生理标测和射频消融

目的 研究静滴不同浓度乙酰甲胆碱（Mach）诱发的犬心房颤动（AF）模型,观察电生理标测及不同部位射频消融的结果。方法 实验选用6只犬。于低浓度、中等浓度及高浓度Mach静滴时诱发AF并行电生理标测。低浓度时3只犬先作上腔静脉至下腔静脉的右房后侧壁线性消融,再作右房前侧壁的线性消融。3只犬仅作右房前侧壁的线性消融。中等浓度时作Bachmann’s束（BB）的射频消融。高浓度时选择电生理标测到的规则周期波部位作局部射频消融。结果 低浓度Mach［（1.04±0.37）μg/(kg·min)］介导的AF,右房小梁部心内电图较间隔部及左房相对紊乱且周长较短。对该部位作射频消融可使AF不被诱发,但提高Mach浓度后即不再有效。中等浓度Mach［（2.70±0.49）μg/(kg·min)］介导的AF,左房及间隔部心内电图较小梁部相对紊乱且周长较短。BB消融后5只犬AF终止,4只不再被诱发,但倍增Mach浓度后,该部位的消融亦不再有效。高浓度Mach ［（5.42±0.97）μg/(kg·min)］介导的AF,2例分别于BB左侧及左心耳基底部记录到局部规则周期波,其中1例行局部射频消融后,AF终止,但仍可再诱发。结论 低浓度Mach介导的AF,右房小梁部是其发生的关键部位。中等浓度Mach介导的AF,房间隔或左房是其发生和维持的关键部位。高浓度Mach介导的AF有局灶起源部位。不同浓度Mach介导AF的有效消融区域不同。     

低强度自主神经节刺激对心房电生理特性的影响

目的研究6h低强度自主神经节（GP）刺激对犬心房电生理性质的影响。方法22只成年杂种犬开胸暴露心脏,在左右心房、左右心耳及肺静脉缝置多极电极导管用以记录和刺激。实验组16只犬同时在左上GP及右前GP予以6h低强度高频刺激（0．1—1．0V）,使心率下降10％。对照组6只犬在心房远离GP处给于同样6h低强度刺激（无心房激动）。刺激前、刺激开始时及6h刺激后测定各部位有效不应期（ERP）及心房颤动（房颤）易颤窗口（WOV）。结果在实验组犬中,GP刺激开始时ERP及WOV较刺激前差异均无统计学意义,GP刺激6h后各部位ERP均显著缩短,总WOV显著增加（127＋35对0对0,P〈O．05）。对照组中,刺激前、刺激开始时及刺激6h后ERP及WOV（3±2对0对0,P〉0．05）差异均无统计学意义。结论6h低强度GP刺激可致心房电生理性质显著改变,并有利于房颤发生,提示长期低强度自主神经系统激活可形成有利于房颤发生的电生理基质。     

The mechanisms of an increased dominant frequency in the left atrial posterior wall during atrial fibrillation in acute atrial dilatation

BACKGROUND: Previous studies have shown that the highest dominant frequency (DF) is located in the left atrium (LA) during atrial fibrillation (AF) in pacing-induced AF. However, there have been few studies on the mechanisms of the increased DF of AF during acute atrial dilatation. The purpose of this study was to investigate the mechanisms of the increased maximal DF (max DF) in pacing-induced AF during acute atrial dilatation. METHODS: In eight Langendorff-perfused canine hearts (26 +/- 2 kg), noncontact balloon catheters were placed into the right atrium (RA) and LA, respectively. AF was induced by extrastimulation pre- and postdilatation in the atrium (0 and 15 cm H(2)O, respectively). Fast Fourier transformation analysis was performed to analyze the max DF and harmonic index (HI) from the bi-atrial unipolar virtual electrograms during AF. The fibrillation cycle lengths were obtained from different atrial sites. The number of wavefronts was analyzed during AF. The frequency of regional splitting was defined as the number of wavefront splits per second in different atrial regions during AF. The percentage of the low-voltage zones (<0.5 mV) was defined as the ratio of the area of the low-voltage zones to the total atrial surface area. RESULTS: The DF was measured during AF. The shortest fibrillation cycle length was located in the LA posterior wall and became shorter during acute atrial dilatation. The max DF was located in the LA posterior wall and increased during acute atrial dilatation (7.1 +/- 0.8 vs 8.8 +/- 2.1, P = 0.02). The max DF of the LA correlated with the wavefront number (r = 0.797, P < 0.001 predilatation; r = 0.860, P < 0.001 postdilatation). The splitting of wavefronts facilitated the formation of new wavefronts. During acute atrial dilatation, the frequency of regional splitting was closely correlated with the percentage of the low-voltage zones (r = 0.876, P < 0.001). Furthermore, the LA posterior wall had a higher percentage of the low-voltage zones than the other sites. CONCLUSION: In acute atrial dilatation, the percentage of the low-voltage zones increased, especially in the LA posterior wall, which correlated with the regional splitting of the AF wavefronts. The increase in the splitting facilitated the formation of new wavefronts and resulted in a higher max DF during acute atrial dilatation.     

Catheter ablation of persistent atrial fibrillation: The importance of substrate modification

Accumulating data have shown that elimination of atrial fibrillation (AF) sources should be the goal in persistent AF ablation. Pulmonary vein isolation, linear lesions and complex fractionated atrial electrograms (CFAEs) ablation have shown limited efficacy in patients with persistent AF. A combined approach using voltage, CFAEs and dominant frequency (DF) mapping may be helpful for the identification of AF sources and subsequent focal substrate modification. The fibrillatory activity is maintained by intramural reentry centered on fibrotic patches. Voltage mapping may assist in the identification of fibrotic areas. Stable rotors display the higher DF and possibly drive AF. Furthermore, the single rotor is usually consistent with organized AF electrograms without fractionation. It is therefore quite possible that rotors are located at relatively “healthy islands” within the patchy fibrosis. This is supported by the fact that high DF sites have been negatively correlated to the amount of fibrosis. CFAEs are located in areas adjacent to high DF. In conclusion, patchy fibrotic areas displaying the maximum DF along with high organization index and the lower fractionation index are potential targets of ablation. Prospective studies are required to validate the efficacy of substrate modification in left atrial ablation outcomes.     

Unique autonomic profile of the pulmonary veins and posterior left atrium.

OBJECTIVES: The purpose of this study was to investigate the electrophysiologic profile of the pulmonary veins (PVs) and left atrium (LA) in response to autonomic manipulation. BACKGROUND: The parasympathetic innervation of the PVs and posterior left atrium (PLA) is thought to contribute to focal atrial fibrillation (AF). We hypothesized that autonomic effects would be more prominent in these regions. METHODS: In 14 dogs, epicardial mapping was performed in the PVs, PLA, and left atrial appendage (LAA) under the following conditions: baseline, 20-Hz cervical vagal stimulation (VS), propranolol (P), P + VS, and P + atropine. Effective refractory periods (ERPs) were measured, and conduction vectors were computed at multiple sites. Western blotting and immunostaining were performed for IKAch (Kir3.1/3.4). RESULTS: The VS and P + VS caused more ERP shortening in the PV and PLA than in the LAA. The P + atropine caused greatest ERP prolongation in the LAA. Cumulative ERP change (ERP difference between P + VS and P + atropine) was greatest in the LAA and corresponded with expression of Kir3.1/3.4 (LAA > PLA > or = PV). The ERP change in response to vagal manipulation was most heterogeneous in the PLA; this corresponded with a pronounced heterogeneity of Kir3.1 distribution in the PLA. With VS and/or P, there was evidence of regional conduction delay in the PVs with a significant change in activation direction. Similar activation changes were not seen in the PLA and LAA. CONCLUSIONS: The PVs and PLA demonstrate unique activation and repolarization characteristics in response to autonomic manipulation. The heterogeneity of vagal responses correlates with the pattern of IKAch distribution in the LA. The peculiar autonomic characteristics of the PVs and PLA might create substrate for re-entry and AF.     

Differences in the characteristics of induced and spontaneous episodes of ventricular fibrillation.

AIMS: The degree of organization of ventricular fibrillation (VF) can be examined in terms of the regularity of the electrical activity within the ventricle. Using electrograms (EGMs) stored within implanted cardioverter defibrillators (ICDs), we examined the hypothesis that the degree of organization, or regularity, was different if the VF was induced by electrical stimulation as opposed to occurring clinically due to ischemia or scar. METHODS AND RESULTS: We compared the statistical characteristics of EGMs recorded by ICDs during spontaneous episodes with those induced during device testing in the laboratory in nine subjects. Regularity of the VF EGM signals was quantified using autocorrelation, Shannon entropy (derived from cycle to cycle activation complexes), and Kolmogorov entropy (derived from eight second long episodes of VF). All three measurements showed a statistically greater degree of regularity for induced VF than in spontaneous episodes. CONCLUSION: Analysis of VF EGMs using these techniques is novel and robust, providing a new way for assessing electrical organization during VF. The clinical significance and utility of differences in VF waveform regularity is unclear at this stage.     

消融犬Marshall韧带对刺激心房左后脂肪垫所致心房颤动的影响及机制

目的探讨消融犬Marshall韧带对刺激心房左后脂肪垫所致心房颤动(简称房颤)的影响及机制。方法成年杂种犬14条,随机分为实验组8条,对照组6条。实验组首先测量左肺静脉和左心耳的有效不应期,继而刺激心房左后脂肪垫诱发房颤。消融Marshall韧带上段后和下段后重复上述步骤。对照组除不干预Marshall韧带外,其它电刺激方案与实验组相同,同时对该组犬的心脏进行迷走神经染色。结果①实验组消融Marshall韧带后,左肺静脉和左心耳的有效不应期均显著延长(P0.05)。②和消融前比较,实验组消融Marshall韧带上段后的房颤诱发率有下降趋势(70.8%vs87.5%,P0.05);消融Marshall韧带全程后房颤诱发率显著下降(33.3%,P0.001)。对照组三次电刺激所测得的不应期和房颤诱发率无差异。③Marshall韧带与左下肺静脉、心房左后脂肪垫、左心耳之间存在迷走神经的直接联系。结论消融犬Marshall韧带可显著降低刺激心房左后脂肪垫所致房颤的诱发率。     

迷走神经刺激和乙酰胆碱灌注对心房肌电生理特性的影响

研究在体情况下迷走神经刺激(VNS)和乙酰胆碱(Ach)灌注对心房肌不同部位的电生理影响,并探讨其诱发心房颤动(AF)的机制。10只杂种犬自身随机对照,运用单相动作电位(MAP)记录技术,同步记录10只开胸犬的右心耳(RAA)、高位右房(HRA)、低位右房(LRA)、左心耳(LAA)、高位左房(HLA)、低位左房(LLA)的MAP,分别给予切断迷走神经、VNS、Ach灌注(分别做为对照组、VNS刺激组、Ach灌注组)后,观察诱发AF的情况和动作电位时程APD50、APD90和APD离散(dAPD)的变化。结果:10只犬在VNS刺激和Ach灌注同时,右心耳单一刺激分别有7只和6只犬诱发AF;VNS明显缩短APD50、APD90,其中RAA缩短最明显(APD50从72±5ms到19±4ms,APD90从136±7ms到43±5ms,P<0.001);Ach灌注也明显缩短APD50和APD90,与VNS相比,LLA的APD90缩短更明显(47±6msvs62±8ms,P<0.01);VNS明显升高心房肌APD50和APD90的离散(17±5msvs7±3ms,25±7msvs8±5ms,P<0.01)。结论:VNS和Ach灌注可引起APD缩短和离散升高,但影响的部位和程度稍有差异,都易诱发AF。     

心力衰竭犬心房组织MMP-2和TIMP-1、2的基因表达及其与心房扩大及心房颤动的关系

目的探讨心力衰竭(简称心衰)犬心房组织基质金属蛋白酶-2(MMP-2)及其组织抑制因子1、2(TIMP-1、2)的基因表达及其与心房扩大及心房颤动(简称房颤)发生维持的关系。方法选健康成年杂种犬14只随机分为心室快速起搏致心衰组和对照组,采用Burst刺激诱发房颤,逆转录-聚合酶链式反应技术和免疫组化方法检测两组左右心房组织MMP-2和TIMP-1、2的mRNA和蛋白表达,采集心房标本前超声心动图测定左右心房收缩末期面积。结果心衰组左室射血分数下降、房颤的诱发和维持时间增加,左右心房均扩大。MMP-2的mRNA和蛋白表达在左右心房中均上调;TIMP-2的mRNA在左右心房中无明显改变,但MMP-2/TIMP-2的mRNA和蛋白的比值在左右心房中均升高(P<0.01);TIMP-1的mRNA和蛋白表达在左右心房中均下调。心衰组,房颤持续时间与左房面积呈正相关。结论心房组织MMP-2和TIMP-1、2的基因表达改变以及MMP-2/TIMP-2表达失衡可能是心衰时心房扩大及房颤发生与维持的分子机制之一。     

Histologic assessment of right atrial appendage myocardium in patients with atrial fibrillation after coronary artery bypass graft surgery

Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac surgery, its pathophysiology is incompletely understood. Our previous study demonstrated that age and left atrial enlargement were independent predictors of postoperative AF. Accordingly, the purpose of this study was to determine whether cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in patients who subsequently developed postoperative AF. Right atrial appendage tissue was obtained during atriotomy in patients undergoing elective CABG surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red stain, and atrial cell diameter was measured with the HE stain. Linear regression, t test, chi2 test or Fisher exact test were used for statistical analysis. Sixty-one patients (mean age 71 +/- 8 years) were studied. Increasing age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06-0.55, p = 0.017). The amount of right atrial fibrosis tended to correlate with the incidence of postoperative AF (p = 0.08). Cell diameter was not significantly different between patients with versus without postoperative AF (p = 0.85). These results suggest that the age-related atrial fibrosis rather than cellular hypertrophy may be important in the pathogenesis of AF after CABG surgery and should be further investigated.