丹参酮ⅡA磺酸钠对家兔快速心房起搏时心房动作电位及有效不应期的影响

研究丹参酮ⅡA磺酸钠(TSN)对家兔短期快速心房起搏时在体心房单相动作电位(AMAP)及心房有效不应期(AERP)的影响,探讨其防治心房颤动的可能机制。家兔24只,随机分为对照组与TSN组各12只。将电极经颈内静脉置入右房记录AMAP,观察基础状态下、给药后0.5h及以600次/分心房快速起搏后0.5,8hAMAP及其频率适应性的变化。结果:与起搏前相比对照组在S1S1200ms刺激时测量的AERP(AERP200)在起搏后0.5h缩短21.2ms,起搏后8h缩短21.6ms(P<0.05),且心房肌的频率适应性丧失。TSN在基础状态下对AMAPA、AMAPD无明显影响,但使AERP200由105.9±3.8ms延长至114.7±7.2ms(P<0.05)。起搏后TSN组维持原有的心房肌频率适应性。结论:快速心房起搏使心房肌的频率适应性丧失而致电重构,TSN能减轻短期快速心房起搏所致电重构。     

伊贝沙坦对快速心房起搏家兔心房电重构的影响

目的观察伊贝沙坦对心房快速起搏8h家兔心房电重构及心房肌细胞超微结构改变的影响。方法将12只家兔随机分为伊贝沙坦组和对照组。经颈内静脉将电极置入右心房,以600次/min行快速心房起搏,分别测定起搏前及起搏后0.5h、1h、4h、8h及停止起搏后10min、20min、30min,S1S1为200ms、150ms时的心房有效不应期(AERP200、AERP150);取未起搏家兔及每组起搏8h后家兔右心耳组织观察超微结构。结果①心房快速起搏8h,对照组家兔AERP缩短,起搏0.5h内AERP缩短幅度最明显;AERP频率自适应性出现了下降—逆转;停止起搏后30minAERP及AERP频率自适应性基本恢复至起搏前水平(最初10min恢复迅速)。②伊贝沙坦组家兔8h心房快速起搏过程中各时间点AERP较起搏前无明显变化。③8h心房快速起搏后对照组家兔心房肌细胞超微结构可见线粒体肿胀、脊溶解、糖原聚集,伊贝沙坦组家兔心房肌细胞超微结构基本正常。结论伊贝沙坦可阻止8h心房快速起搏所致的心房电重构和心房肌细胞超微结构改变。     

氯沙坦对家兔快速心房起搏心房电重构及L-型钙通道的影响

目的:通过人工心脏起搏的方法制备家兔急性心房颤动(Af)动物模型,探讨Af时心房发生电重构的机制,并观察氯沙坦对电重构的影响.方法:30只家兔,随机分为3组(每组10只):对照组、0.9%氯化钠起搏组、氯沙坦起搏组;以600次/min的频率起搏心房8 h,并分别于起搏后2、4、6、8 h测定心房有效不应期(AERP)变化及L-型钙通道的电流密度.结果:①经快速起搏8 h,0.9%氯化钠起搏组较对照组各个基础周长下的AERP均显著下降.氯沙坦起搏组较对照组AERP无明显变化.②0.9%氯化钠起搏组较对照组心房肌ICa-L降低;氯沙坦起搏组较对照组心房肌ICa-L未见显著降低;氯沙坦起搏组较0.9%氯化钠起搏组心房肌ICa-L差异无统计学意义,但ICa-L的标准差显著降低.结论:①快速心房起搏可引起AERP缩短及AERP频率适应性不良为特征的心房肌电重构,氯沙坦可以预防电重构的发生.②快速心房起搏可以导致心房肌ICa-L的降低和离散度的增高;氯沙坦可以抑制ICa-L离散度的增加从而降低Af的潜在危险.     

氯沙坦对家兔快速心房起搏心房肌细胞超微结构的影响

20只家兔随机分为生理盐水组、氯沙坦组,分别灌胃给药1周,以600次/分的频率起搏心房8h后,生理盐水组心房肌细胞可见线粒体肿胀、变形、嵴排列紊乱,部分可见断裂、融合或消失,糖原颗粒聚集、溶解,部分心肌肌节排列紊乱。氯沙坦组上述变化较轻。结论:氯沙坦可以减轻短期快速心房起搏所致的细胞超微结构的改变。     

普伐他汀对快速起搏心房肌结构重构的影响

目的 通过普伐他汀干预快速起搏的心房肌，观察普伐他汀对快速起搏心房肌结构重构的作用，从而探讨他汀药治疗心房颤动(房颤)的机制及可行性。方法 将17条犬分为对照组、起搏组及干预组。对照组不给任何处理及干预；起搏组采用快速起搏心房的方法建立房颤模型，分别给犬植入420—500次／min的固定频率起搏器，起搏时间为4周。干预组以同样的方法植入起搏器并同时服用普伐他汀4周。采用超声心动图检查起搏组及干预组起搏前及起搏、干预4周后左心房前后径及各项容量指标。分别取3组犬左心耳心房肌进行苏木精-伊红及Masson染色，观察细胞形态，有无炎细胞浸润及纤维化情况。结果 (1)心脏超声部分：起搏组术后4周与术前比左心房前后径及各项容量指标均有显著增加，干预组术后4周与术前比差异无显著性；(2)组织细胞学检查部分：对照组，肌纤维排列整齐，胞浆染色均匀，间质无炎细胞浸润。起搏组胞膜不清，胞浆淡染，部分细胞可见空泡变性及片状粘液变性。间质可见炎细胞浸润，可见间质及心肌细胞纤维化。干预组，部分细胞胞膜不清，胞浆淡染，无炎细胞浸润，无间质及心肌细胞纤维化。结论 普伐他汀可显著抑制快速起搏引起的心房结构重构。     

粉防已碱对家兔快速心房起搏所致电重构的影响

为探讨家兔快速心房起搏所致的心房肌电重构的机制及粉防已碱对其影响 ,32只家兔随机分为三组 :正常对照组 (A组 ,n =8) ,快速心房起搏组 (B组 ,n =12 ) ,快速心房起搏 +粉防已碱组 (C组 ,n =12 )。经颈内静脉将电极置入右房 ,以 6 0 0次 /分行快速心房起搏 ,测定基础状态、给药后 0 .5h和起搏后 0 .5 ,1,2 ,4 ,6 ,8h ,S1S1为 2 0 0 ,15 0 ,130ms时的心房有效不应期 (AERP2 0 0 、AERP150 和AERP13 0 ) ,实验结束后取三组兔的右心耳组织 ,检测心肌细胞内Ca2 + 含量 ,观察心肌细胞超微结构。结果 :快速心房起搏后B组的AERP缩短 ,AERP的频率适应不良 ,心肌细胞内Ca2 + 含量增加 ,同基础状态比较差异有显著性 (P <0 .0 1) ,心房肌细胞损伤的超微结构变化明显 ,在C组粉防已碱抑制了快速起搏引起的心肌细胞Ca2 + 增加 ,AERP缩短和频率适应不良减轻。结论 :心房肌细胞内Ca2 + 水平的增高在快速起搏导致的心房肌电重构中起作用 ,粉防已碱能减轻快速心房起搏所致的电重构。     

短时间快速右心房起搏致犬心房电重构、收缩重构及解剖重构的实验研究

目的通过对快速心房起搏犬的电生理特性、收缩功能及超微结构的研究,观察短时间快速心房电活动是否可引起心房重构,并探讨其在房颤持续中的作用。方法健康杂种犬17只。实验组12只,经右心耳起搏450次／min,持续5小时。快速心房刺激前后分别测量P波时程及心房有效不应期,并用多普勒超声评价二尖瓣前向血流变化。实验结束后取左心耳及梳状肌组织观察其超微结构。对照组5只,插入电极但不起搏,与实验组同步行各项检查。结果持续快速刺激5小时后,实验组心房有效不应期降低,P波时程增加;二尖瓣心房收缩期血流速度降低了17％;检查发现部分心肌细胞出现肌原纤维的损失、糖原累积及线粒体大小及形状的改变;而对照组均未发现明显变化。结论短时间快速心房电活动可导致犬心房发生电重构、收缩重构及结构重构,而心房结构重构可能是心房发生电重构和收缩重构的原因之一。     

不同部位及不同方式心房起搏对心房激动的影响

目的 了解不同部位、不同方式心房起搏时P波、P－R间期以及心房激动顺序的特点，从而寻找最佳的心房单部位起搏方式。方法 对20例射频消融成功后的患者，分别放置高位右房、右心耳、Koch三角、希氏束以及冠状窦电极，若为左侧旁路则加置左心房电极，行不同部位、不同方式心房起搏。结果 Koch三角、Koch三角＋高位右房、左房、双房起膊时P波宽度、P－R间期无差异，但右心耳起搏时各导联P波增宽，P－R间期延长。从心房激动顺序分析，右心耳起搏时，激动传至希氏束区及冠状窦区的时间最长，而Koch三角、Koch三角＋高位右房及双房起搏时则较短，尤其是Koch三角、Koch三角＋高位右房起搏缩短更明显。另外，不同部位、不同方式起搏时右心房压力无差异。结论 Koch三角起搏在某种程度上可替代高位右房＋冠状窦起搏及双房起搏。     

贝那普利对快速心房起搏家兔心房电重构的影响

目的 观察贝那普利对8h心房快速起搏家兔心房电重构(AER)的影响。方法取12只家兔,随机分为二组,对照组(生理盐水15ml/d),贝那普利组[5mg/(kg·d)溶于15ml生理盐水中],灌胃2周。①分别于起搏前、中、后测刺激频率为200ms、150ms时心房有效不应期(AERP200、AERP150)。②取未起搏家兔及每组起搏8h后家兔右心耳组织观察超微结构。结果①8h心房快速起搏使对照组家兔AERP缩短,AERP频率自适应性出现了下降—消失—逆转,心房肌超微结构可见线粒体肿胀、嵴溶解,糖原聚集;停止起搏后30min AERP及AERP频率自适应性基本恢复。②贝那普利组家兔心房快速起搏8h过程中各观测点AERP较起搏前无明显变化,家兔心房肌细胞超微结构基本正常。结论①心房快速起搏8h可致AER和心房肌细胞发生超微结构改变。②贝那普利可以阻止心房快速起搏8h所致AER及心房肌超微结构改变。     

快速心房激动对心房肌电生理特性的影响

比较快速心房起搏与急性心房颤动 (简称房颤 )诱发心房电生理特性的变化。以 15 0～ 2 0 0ms起搏周长(PCL)对 4 5例成功射频消融后 (RFCA)病人右房进行S1S1刺激诱发急性房颤 ,据能否诱发急性房颤分为非房颤组和急性房颤组 ;再以 4 0 0msPCL对心房快速激动前后高位右房、低位右房、His束周围等多部位进行S1S2 扫描 ,测定心房有效不应期 (ERP)、ERP离散度 (ERPd)、右房内及房间的传导时间的变化 ;另以 35 0 ,4 0 0和 4 5 0ms三个PCL随机对RAA进行S1S2 扫描 ,观察ERP频率自适应性的变化。两组心房快速激动后 4 0 0msPCL下右房各刺激部位及三种不同PCL右心耳ERP均较心房快速激动前有明显的缩短 ,并且缩短的程度相同。两组病人心房快速激动前后房内和房间传导时间及ERPd没有明显改变。两组心房快速激动前后斜率均值均较激动后明显下降 ;心房快速激动前、后斜率均值两组间无显明差别 (P >0 .0 5 )。结论 :两种方式的心房快速激动可诱发相似的心房电重构现象。     

Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery.

OBJECTIVES: Our goal was to evaluate the role of myocardial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and plasma markers of oxidative stress in the pathogenesis of post-operative atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is a common complication of cardiac surgery, leading to increased morbidity and prolonged hospitalization. Experimental evidence suggests that oxidative stress may be involved in the pathogenesis of AF; however, the relevance of this putative mechanism in patients undergoing cardiac surgery is unclear. METHODS: We measured basal and NADPH-stimulated superoxide production in right atrial appendage samples from 170 consecutive patients undergoing conventional coronary artery bypass surgery. Plasma markers of lipid and protein oxidation (thiorbabituric acid-reactive substances, 8-isoprostane, and protein carbonyls) were also measured in blood samples drawn from a central line before surgery and after reperfusion. RESULTS: Patients who developed AF after surgery (42%) were older and had a significantly increased atrial NADPH oxidase activity than patients who remained in sinus rhythm (SR) (in relative light units/s/mug protein: 4.78 +/- 1.44 vs. 3.53 +/- 1.04 in SR patients, p < 0.0001). Plasma markers of lipid and protein oxidation increased significantly after reperfusion; however, neither pre-operative nor post-operative measurements differed between patients who developed AF and those who remained in SR after surgery. Multivariate analysis identified atrial NADPH oxidase activity as the strongest independent predictor of post-operative AF (odds ratio 2.41; 95% confidence interval 1.71 to 3.40, p < 0.0001). CONCLUSIONS: Atrial NADPH oxidase activity is independently associated with an increased risk of post-operative AF, suggesting that this oxidase system may be a key mediator of atrial oxidative stress leading to the development of AF after cardiac surgery.     

尼克酰胺腺嘌呤二核苷酸对阿霉素所致大鼠心肌损伤的保护作用

目的观察尼克酰胺腺嘌呤二核苷酸(NADH)对阿霉素(ADR)损伤的大鼠心肌保护作用。方法将60只雄性健康Wistar大鼠随机分为ADR组、NADH组、ADR NADH组及对照组。在实验第8周处死大鼠.光镜下观察心肌形态结构及病理改变;用生化方法测定大鼠心肌组织、心肌细胞线粒体中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)水平。结果光镜下ADR NADH组大鼠心肌组织损伤程度较ADR组明显减轻;从心肌组织GSH-Px、SOD活性可以看出,与ADR组[(3.97±1.11.15.63±3.79)kU/g Pr]比较,ADR NADH组[(5.88±0.97,49.27±4.22)kU/g Pr]明显增高,二者比较差异有统计学意义(q=7.22、32.18,P<0.01);心肌组织MDA水平,ADR组[(4.55±1.51)μmoI/g Pr]明显高于ADR NADH组[(3.64±0.75)μmoL/g Pr],二者比较差异有统计学意义(q=8.48,P<0.01)。结论NADH对阿霉素性心肌损伤有一定的保护作用,这种保护作用可能主要与NADH提高受损心肌细胞抗氧化能力有关。     

心房颤动电重构的实验研究

目的 :研究犬心房颤动 (Af)模型心房有效不应期 (ERP)的变化 ,验证Af电重构这一假说的正确性。方法 :采用快速心房起搏的方法建立犬的Af模型 (起搏组 ,n =13) ,用程序刺激测量心房的ERP ;观察P波时限和PA间期的变化 ,并与假手术组 (对照组 ,n =7)作比较。结果 :持续快速起搏 9～ 10周后 ,心房ERP明显缩短 ,当S1S1为 30 0ms时 ,对照组与起搏组分别为 (15 0± 2 1)ms与 (115± 2 3)ms(P<0 .0 1) ;S1S1为 4 0 0ms时分别为(15 4± 2 4 )ms与 (10 5± 2 7)ms(P <0 .0 1)。起搏组P波时限和PA间期明显长于对照组。结论 :持续心房快速刺激可使ERP明显缩短 ,使心房发生电重构。心房电重构可促进Af的发生和发展     

Molecular basis of electrical remodeling in atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is often associated with other cardiovascular disorders and diseases. AF can lead to thromboembolism, reduced left ventricular function and stroke, and, importantly, it is independently associated with increased mortality. AF is a progressive disease; numerous lines of evidence suggest that disease progression results from cumulative electrophysiological and structural remodeling of the atria. There is considerable interest in delineating the molecular mechanisms involved in the remodeling that occurs in the atria of patients with AF. Cellular electrophysiological studies have revealed marked reductions in the densities of the L-type voltage-gated Ca2+ current, I(Ca,L), the transient outward K+ current, I(TO), and the ultrarapid delayed rectifier K+ current, I(Kur), in atrial myocytes from patients in chronic AF. Similar (but not identical) changes in currents are evident in myocytes isolated from a canine model of AF and, in this case, the changes in currents are correlated with reduced expression of the underlying channel forming subunits. In both human and canine AF, the reduction in I(Ca,L) appears to be sufficient to explain the observed decreases in action potential duration and effective refractory period that are characteristic features of the remodeled atria. In addition, expression of the sarcoplasmic reticulum Ca2+ ATPase is reduced, suggesting that calcium cycling is affected in AF. These recent studies suggest that calcium overload and perturbations in calcium handling play prominent roles in AF-induced atrial remodeling. Although considerable progress has been made, further studies focused on defining the detailed structural, cellular and molecular changes that accompany the different stages of AF in humans, as well as in animal models of AF, are clearly warranted. It is anticipated that molecular insights gleaned from these studies will facilitate the development of improved therapeutic approaches to treat AF and to prevent the progression of the arrhythmia.     

β1肾上腺素能受体自身抗体表达增强对心房颤动及心房电重构的影响

目的探讨β1肾上腺素能受体自身抗体(β1AR)表达增强对心房颤动(简称房颤)及心房电重构的影响。方法 24只新西兰大白兔随机分为对照组(Con组)和β1AR组。β1AR组给予2 mgβ1受体细胞外第二环功能表位肽段与佐剂背部皮下多点注射,对照组给予佐剂背部皮下多点注射。每2周注射1次,共4次。于0、2、4、6 W采耳缘静脉血,离心取血清通过酶联免疫吸附测定血清中抗体滴度,验证造模是否成功。每只兔子在免疫前后,采用S_1S_2递减刺激测量心房有效不应期(AERP),通过Burst刺激测量房颤诱发率和持续时间。免疫结束后取心房肌组织进行蛋白免疫印记法检测各组内离子通道蛋白(Kir3.1及Cav1.2)和缝隙连接蛋白(Cx43和Cx40)总量的表达变化,逆转录聚合酶链反应分析上述指标各组内mRNA的表达变化。结果①与0 w比较,β1AR组在2、4和6 w血清中β1AR水平逐渐增加(P<0.05),而Con组内各个时间点血清中β1AR水平无差异(P>0.05);与Con组相比,除0 w两组比较无差异外,其余β1AR组血清中β1AR水平高于Con组(P<0.05)。②β1AR组免疫后较免疫前AERP缩短[(65±8.5)ms vs (116±23.4)ms,P<0.05],平均心率显著增快[(290±35.3)次/分vs (187±31.1)次/分,P<0.05];与Con组相应时间比较,β1AR组免疫后均出现AERP缩短[(65±8.5) ms vs (116±25.3)ms,P<0.05]和平均心率增快[(290±35.3)次/分vs (198±13.7)次/分,P<0.05]。③β1AR组免疫后较免疫前房颤诱发率增加[83.3%(10/12) vs 0(0/12),P<0.05]及持续时间延长[(24.66±40.92)s vs (0±0)s,P<0.05];与Con组相应时间比较,β1AR组房颤诱发率显著增加[83.3%(10/12) vs 0(0/12),P<0.05]及持续时间延长[(24.66±40.92)s vs (0±0)s,P<0.05];④与Con组相比,β1AR组Cx43和Cav1.2蛋白水平及mRNA水平显著降低(P<0.05)。Kir3.1及Cx40蛋白水平及mRNA含量显著升高(P<0.05)。结论β1AR表达增强能缩短AERP,增加房颤易感性和持续时间,通过改变离子通道特性造成心房肌电重构,促进房颤的发生和维持。     

心房电重构与房颤关系的基础研究

目的检查观测心房电生理改变与房颤（AF）发生和持续的关系,探讨心房电重构与房颤的内在联系。方法健康成年杂种犬14只（雌雄不拘,体重10．0～12．5kg）,随机分为2组：对照组（A组）和起搏组（B组）。右侧开胸将电极置于右心房,以400次／min的频率快速起搏右心房（A组只手术不起搏）,分别于实验开始及起搏6h后对每只犬进行电生理检查,测定心房有效不应期（AERP）。起搏开始及起搏后测定burst刺激诱发房颤的频率和持续时间。结果A组在整个时间内AERP无变化,B组心房快速起搏后,AERP明显缩短。A、B两组起搏前房颤的频率和持续时间差异无统计学意义。A组起搏前、后房颤的频率和持续时间无变化,B组心房快速起搏后房颤的频率增多,持续时间延长。结论快速心房起搏可以引起心房有效不应期缩短,即心房电重构。心房电重构造成的心房有效不应期等电生理变化促进了房颤的发生和维持,是心房电重构与房颤关系的基础。     

Ionic mechanisms of electrical remodeling in human atrial fibrillation

OBJECTIVES: Atrial fibrillation (AF) is associated with a decrease in atrial ERP and ERP adaptation to rate as well as changes in atrial conduction velocity. The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood. METHODS: Action potentials (AP) and ionic currents were studied with the patch clamp technique in single atrial myocytes from patients in chronic AF and compared to those from patients in stable sinus rhythm (SR). RESULTS: The presence of AF was associated with a marked shortening of the AP duration and a decreased rate response of atrial repolarization. L-type calcium current (ICa,L) and the transient outward current (Ito) were both reduced about 70% in AF, whereas an increased steady-state outward current was detectable at test potentials between -30 and 0 mV. The inward rectifier potassium current (IKI) and the acetylcholine-activated potassium current (IKACh) were increased in AF at hyperpolarizing potentials. Voltage-dependent inactivation of the fast sodium current (INa) was shifted to more positive voltages in AF. CONCLUSIONS: AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia.