离体家兔心脏房压增加所致的心房肌电生理特性变化及机制

目的：探讨心脏房压增加引起的心脏电生理变化及链霉素（牵张激活性离子通道阻断剂）和维拉帕米对其的影响。方法：采用结扎腔静脉和肺静脉、贯通房间隔、调节肺动脉灌注压（5 cmH₂O到25 cmH₂O）的离体Langendorff心脏模型，观察房压增加前后心肌有效不应期（ERP）、单相动作电位时程MAPD₉₀和房颤阈（AFT）的变化，并比较链霉素和维拉帕米对这些电生理参数变化的影响。结果：房压上升（20 cmH₂O）引起ERP和MAPD₉₀缩短，AFT下降（P<0.01）；链霉素可有效抑制这些电生理变化；而维拉帕米对此没有明显影响。结论：牵张激活性离子通道的活化可能参与房压增加引起的心脏电生理变化过程。     

改变左心室后负荷和离体兔心脏对阈下条件串刺激引起的心室不应期变化的影响

目的:探讨改变左心室后负荷和兔离体灌注心脏对阈下条件串刺激引起的心室不应期变化的影响。方法:采用阈下条件刺激(S_t)法心室不应期测定技术,测定改变左心室后负荷和去除神经,体液因素作用时,S_t法心室不应期强度间期关系特征。结果:减小左室后负荷,可使S_t法测定的心室不应期延长(P＜ 0.05, P＜ 0.01);且在各刺激强度的S_t,S_t(200 Hz,100 ms)和S_t(50 ms, 100 Hz)测定的心室不应期最长(P＜ 0.05,P＜0.01)。结论:改变左心室后负荷和去除神经体液因素作用可使S_t法心室不应期强度间期关系特征发生改变。     

犬希氏束起搏的心脏电生理和血液动力学效应研究

目的:探讨希氏束起搏电极定位技术及心脏电生理和血液动力学变化特点。方法:健康犬在全麻呼吸机通气下,开胸,将特制希氏束(HisB)标测/起搏电极进行HisB电位标测,确定HisB起搏位点;并将心室起搏电极固定于右室尖部分别构成HisB-_VVI、RVA-_VVI单腔心脏起搏,对比分析其心脏电生理和血液动力学参数变化。结果:HisB起搏阈值参数符合心室起搏要求;HisB-_VVI起搏QRS波较RVA-_VVI起搏变窄;心输出量(CO)较自身增加18.81%,RVA-_VVI起搏反而降低约5.41%;每搏量(SV)接近于自身窦性心律,但明显高于RVA-_VVI起搏约25.59%;左室每搏功(LVSW)和右室每搏功(RVSW)等参数亦明显优于RVA-_VVI心脏起搏。结论:HisB起搏由于将心室起搏位点从传统的右室尖改为His束,从而保持了近于正常生理性心室激动顺序和心室收缩同步性,故可维持整个心脏协调有序的收缩和舒张,产生优于RVA-_VVI起搏的血液动力学效果。     

非兴奋性电刺激对正常及心肌梗死兔心功能的影响及其作用的局部性

目的:观察于绝对不应期发放电刺激对正常和心肌梗死(MI)兔在体心脏心功能的影响及其对心肌作用的局部性。方法:64只家兔随机分为正常组和MI组两大组,每组又分为前壁和后壁两组。复制MI模型,4周后每组开胸,窦性心律下,分别于前壁组和后壁组的左心室前壁和后壁,发放绝对不应期方波电刺激(CCM)。观察左心室收缩压(LVSP)左心室舒张末压(LVEDP)及其微分(±dp/dt_max)的变化。结果:正常组前壁和后壁CCM刺激时LVSP及+dp/dt_max均显著大于刺激前(P<0.05),LVEDP低于、-dp/dt_max负值大于刺激前(P<0.05),且不同部位的CCM刺激对心功能的影响不同,左心室前壁的上述作用大于后壁(P<0.05);MI组前壁和后壁CCM刺激时LVSP及+dp/dt_max亦大于刺激前(P<0.05),LVEDP低于、-dp/dt_max负值亦大于刺激前(P<0.05),但前后壁两组之间无显著差别(P＞0.05)。结论:于绝对不应期发放电刺激能明显增强正常和MI后心肌的收缩和舒张功能,CCM刺激对心肌的作用是局部性的。     

心力衰竭大鼠β3-肾上腺素能受体兴奋对室颤阈值和心室有效不应期的影响

目的: 观察实验性心力衰竭大鼠左心室β₃-肾上腺素能受体(AR)表达水平的变化及β₃-AR激动时对心脏室颤阈值（VFT）和心室有效不应期（ERP）的影响。方法: 雄性成年Wistar大鼠16只，随机分为心力衰竭组（n=8）及对照组（n=8）。结扎大鼠冠状动脉前降支致心肌梗死建立心力衰竭模型；使用RT-PCR法检测左心室β₃-AR mRNA的表达；观察使用β₃-AR激动剂BRL37344对VFT、ERP和LVESP、+dp/dtmax、-dp/dtmax的影响。结果： ①与对照组相比，心力衰竭大鼠左心室β₃-AR mRNA表达量(β₃/β-actin的比值) 增加（0.011 vs 0.028, P<0.05），所占比例(β₃/β₁+β₂+β₃) 增加（1.2% vs 5.4%, P<0.05）；②心力衰竭大鼠VERP较正常对照组VERP明显延长(70.5 ms±5.5 ms vs 59.5 ms±6.4 ms，P<0.05)；静注BRL37344后，心力衰竭大鼠VERP稍延长，但对比用药前VERP无显著差异(73.0 ms±4.8 ms vs 70.5 ms±5.5 ms，P>0.05)；③心力衰竭大鼠VFT较正常对照组VFT显著降低(10.9 mV±0.8 mV vs 30.5 mV±1.3 mV，P<0.05)；静注BRL37344后，心力衰竭大鼠VFT相比用药前亦显著降低(7.1 mV±0.6 mV vs 10.9 mV±0.8 mV，P<0.05)； BRL37344降低VFT的作用与BRL37344对LVESP、+dp/dtmax、-dp/dtmax及β₃-AR mRNA表达量的改变密切相关，相关系数分别为0.788、0.708、0.759、0.787(P<0.05)。结论： 心力衰竭大鼠左心室β₃-AR mRNA表达明显增高，β₃-AR激动时不影响衰竭大鼠心室ERP，但明显降低衰竭大鼠心脏VFT，其降低VFT作用与β₃-AR的负性肌力作用及β3-AR mRNA表达量的改变密切相关。     

低氧时钙离子对冠状动脉内皮细胞释放ET-1、NO、PGI2的影响

目的:探讨低氧引起冠状动脉内皮细胞(CAEC)释放ET-1、NO和PGI₂改变的机制。方法:运用放射性[⁴⁵Ca²⁺]掺入、放免和比色等方法, 测定常氧组、低氧组冠状动脉内皮细胞钙摄取率, 以及常氧组、低氧组、低氧+维拉帕米组冠状动脉内皮细胞培养液中ET-1、NO和PGI₂含量。结果:低氧组CAEC[⁴⁵Ca²⁺]摄取率为(29.6±3.7)ng/gprotein/30min, 常氧对照组为(15.2±1.1)ng/gprotein(P<0.01).低氧+维拉帕米组ET-1分泌量显著多于低氧组(P<0.01).低氧+维拉帕米组分泌的NO显著低于低氧组(P<0.05), 与常氧组相差不显著。低氧+维拉帕米组分泌的PGI₂显著多于低氧组, 与常氧组相差不显著。结论:低氧时引起的NO、ET-1、PGI₂分泌改变与低氧引起的冠状动脉内皮细胞Ca²⁺内流增加有关。     

阿托伐他汀对快速起搏兔房颤模型心房电重构的影响

 目的: 观察阿托伐他汀(ATO)对快速起搏兔房颤模型心房电重构、心房肌离子通道蛋白及心脏功能的影响,探讨阿托伐他汀防治心房颤动的电生理机制。方法: 30只新西兰大白兔开胸植入心房起搏和测试电极,采用特制动物心脏起搏器快速起搏心房的方法建立兔房颤模型,将其分为对照组、起搏组和药物组。药物组预先给予阿托伐汀钙片2 mg·kg^-1·d^-1灌胃7 d,起搏组和药物组快速起搏心房48 h,期间药物组持续给药处理,分别于0 h、8 h、16 h、24 h、32 h、40 h、48 h测量心房有效不应期,计算心房频率适应性,观察心脏大小及心功能的变化,比较各组心房肌细胞离子通道蛋白CaLα1和Kv4.3的表达差异。结果: 与对照组相比,药物组和起搏组心房有效不应期缩短,频率适应性下降,心房肌细胞离子通道蛋白CaLα1及Kv4.3表达水平降低(P<0.05),其中以起搏组变化最为明显。快速起搏心房48 h后,起搏组和药物组左房较对照组增大(P<0.05),而左心室大小及射血分数起搏前后均无明显差异。结论: 短期快速心房起搏可引起心房有效不应期缩短,导致心房频率适应性不良,阿托伐他汀预处理可有效改善快速起搏诱导的兔心房电重构,而对心脏结构影响不大。进一步研究发现阿托伐他汀可在一定程度上抑制心房肌钾、钙离子通道蛋白水平降低,这可能是其改善电重构的机制之一。     

改变在体兔左心室后负荷对其电生理参数的影响

目的：探讨改变在体兔左心室后负荷对室性心律失常发生情况及左心室电生理参数的影响。方法：改变左心室后负荷，观察室性心律失常发生情况，并测定左心室舒张阈值（ＶＤＴ），相对不应期（ＲＲＰ），有效不应期（ＥＲＰ）及其不应期离散和心室纤颤阈（ＶＦＴ）。结果：逐级增加左心室后负荷（ＡＢ级）可使左室空间ＲＲＰ，ＥＲＰ离散增加（Ｂ级，Ｐ＜００５），ＶＦＴ降低（Ｂ级，Ｐ＜００１）；各实验动物均出现室性心律失常（Ｂ级）；而逐级减小左室后负荷（ＣＤ级），心室电生理参数无变化（Ｐ＞００５），各实验动物亦无室性心律失常发生。结论：增加左心室后负荷诱发室性心律失常，与左室空间不应期离散增加有关。     

机械牵张对钙预适应心肌电生理特性的影响

目的：研究在模拟缺氧-复氧再灌注条件下机械牵张对钙预适应(CPC)离体豚鼠乳头肌电生理特性的影响。 方法： 利用细胞内标准玻璃微电极技术，记录并观察一定牵张力（200 mg强度）作用下钙预适应乳头肌细胞动作电位（AP）和有效不应期（ERP）的变化。 结果： 牵张可使单纯缺氧-复氧再灌注（AR）组和CPC组在整个缺氧期除兴奋传导时间（CT）明显延长外，Vmax、RP、APA、APD50、APD90和ERP等参数明显缩短，但对CPC组的影响较小。而牵张可使两组在复氧再灌注期的动作电位的Vmax、RP、APA、APD50和ERP降低，CT和APD90延长，但对CPC组的影响较小。链霉素可抑制机械牵张对CPC组上述参数的影响。 结论： 在模拟缺氧-复氧再灌注条件下，CPC乳头肌对机械牵张的耐受性增强；链霉素则可抑制牵张对CPC心肌电生理特性的影响。     

兔急性心肌缺血时心肌非缺血区的电生理学变化

本研究通过结扎家免在位心脏冠状动脉左室支造成急性心肌缺血。结果显示不仅缺血区心肌有明显的电生理变化，在非缺血区亦有电生理变化，后者主要表现为广泛的非缺血区域有效不应期（ERP）呈普遍轻度延长，与缺血边缘带共同形成一个不应期离散和跃变带。这种电生理紊乱易于诱发折反性心律失常的产生。升高循环血中几条酚胺浓度并不能模拟非缺血区的电生理变化。刺激连走神经外周瑞虽可使自然心律情况下的ERP延长，但却不能使固定心律情况下的ERP延长。提示非缺血区的电生理学变化并非由于心肌缺血时交感或迷走神经张力增高所致，而可能有其它原因。     

Electrophysiological effect of rotigaptide in rabbits with heart failure

Introduction

Rotigaptide is a new anti-arrhythmic peptide, which has recently been found to increase junctional conductance and prevent ischemia-induced ventricular tachycardia. In this study, we attempted to investigate the effects and mechanisms of rotigaptide on the vulnerability to ventricular arrhythmias in rabbits with heart failure (HF).

Material and methods

Chronic volume-pressure overload was used to induce HF. After rotigaptide infusion, an electrophysiological study was performed to record monophasic action potential (MAP), determine the effective refractory period (ERP) and ventricular fibrillation threshold (VFT), and assess the susceptibility to ventricular arrhythmia. Finally, real-time PCR was used to detect the changes of connexin 43 (Cx43) mRNA expression.

Results

HF rabbits exhibited significant down-regulation of Cx43 mRNA, increase of effective refractory period (ERP) and decrease of VFT (p < 0.05, respectively). These changes resulted in an increase of vulnerability to ventricular tachyarrhythmias (VT/VF). Rotigaptide administration shortened ERP (113.3 ±8.6 ms vs. 131.7 ±12.5 ms, p < 0.05), restored VFT (15.0 ±2.0 V vs. 6.3 ±1.4 V, p < 0.05), and decreased the vulnerability to VT/VF. However, short-term rotigaptide treatment had no significant effect on MAP duration (MAP duration at 90% repolarization: 169.3 ±6.0 ms vs. 172.7 ±6.2 ms, p > 0.05) or connexin 43 mRNA expression (p > 0.05).

Conclusions

Rotigaptide decreases the ERP, elevates VFT, and reduces the vulnerability to ventricular arrhythmias without changing Cx43 expression in rabbits with HF. It may be a promising antiarrhythmic drug for preventing ventricular arrhythmia in HF.     

Sensitization by low temperature of the isolated perfused heart to induced ventricular fibrillation

Summary The ventricular fibrillation threshold (VFT) in the perfused isolated heart of rabbits and cats was compared at 37° C and during hypothermia (17° to 34° C). The method consisted in measuring the minimal current of a single square-wave 10 msec pulse which was required to induce fibrillation or tachycardia when applied to the left ventricle during the vulnerable period of late systole.Hypothermia significantly lowered the VFT in both species and reduced the incidence of induced persistent (>60 sec) fibrillation or tachycardia in rabbit hearts so that only a non-persistent arrhythmia could be induced in a high proportion of trials. The vulnerable time (VT), i. e. the minimal delay after the R wave of the e. c. g. at which the single current pulse had to be applied to induce the arrhythmia, was lengthened by the hypothermia; the duration of electrical systole was lengthened to a similar extent as indicated by the unaltered VT:R-T ratio. The total refractory period in rabbit hearts was prolonged more than the duration of electrical systole by cold.The results in this study indicate that in ventricular fibrillation one should attempt to differentiate those factors which initiate the arrhythmia from those which are concerned in its maintenance.     

急性心肌梗塞早期心室易损性的电生理实验研究

本文采用Ｓ１－Ｓ２程控电刺激方法同时测定心室易期和室颤阈，并结合其它有关电生理指标，评价了急性心肌梗塞早期心室易损性。结果表明，急性心肌梗塞早期，心室易损期明显延长，室颤阈显著下降，起搏阈值降低，有效不应期缩短，强度间期曲线下移，心室易损期外缘向Ｔ波方向延伸，联律间期与折回间期呈负相关。根据上述指标分析了急性心肌梗塞早期室性心动过速和／或心室颤动产生的电生理机制以及心室易损期在ｒｏｎＴ室性早搏触发     

Pathomorphology of the heart conduction system: comparative study during increase in left or right ventricular afterload

Pathomorphology of the peripheral compartments of the heart conduction system under conditions of increased left or right ventricular afterload is characterized by interstitial edema, hemorrhages, and reversible and irreversible focal lesions. The percentage of damaged conduction cardiomyocytes increases in the wall of hemodynamically overloaded ventricle and in the ventricular septum. These changes are more pronounced in cases when the afterload increase is complicated by heart failure development. Acute dilatation of the heart and distention of the myocardium are events of great specific significance in the genesis of the conduction system disorders developing under conditions of increased right ventricular afterload in comparison with those developing under conditions of increase left ventricular afterload. These data attest the presence of a pathomorphological base for the appearance of arrhythmias during the acute phase of pressure overload of the heart, especially in cases when it is aggravated by heart failure.     

Granulocyte colony-stimulating factor stabilizes cardiac electrophysiology and decreases infarct size during cardiac ischaemic/reperfusion in swine

Aim: Effects of granulocyte colony‐stimulating factor (G‐CSF) on cardiac electrophysiology during ischaemic/reperfusion (I/R) period are unclear. We hypothesized that G‐CSF stabilizes cardiac electrophysiology during I/R injury by prolonging the effective refractory period (ERP), increasing the ventricular fibrillation threshold (VFT) and decreasing the defibrillation threshold (DFT), and that the cardioprotection of G‐CSF is via preventing cardiac mitochondrial dysfunction. Methods: In intact‐heart protocol, pigs were infused with either G‐CSF or vehicle (n = 7 each group) without I/R induction. In I/R protocol, pigs were infused with G‐CSF (0.33 μg kg^?1 min^?1) or vehicle (n = 8 each group) for 30 min prior to a 45‐min left anterior descending artery occlusion and at reperfusion. Diastolic pacing threshold (DPT), ERP, VFT and DFT were determined in all pigs before and during I/R period. Rat’s isolated cardiac mitochondria were used to test the protective effect of G‐CSF (100 nm ) in H₂O₂‐induced mitochondrial oxidative damage. Results: Neither G‐CSF nor vehicle altered any parameter in intact‐heart pigs. During ischaemic period, G‐CSF significantly increased the DPT, ERP and VFT without altering the DFT. During reperfusion, G‐CSF continued to increase the DPT without altering other parameters. The infarct size was significantly decreased in the G‐CSF group, compared to the vehicle. G‐CSF could also prevent cardiac mitochondrial swelling, decrease ROS production, and prevent mitochondrial membrane depolarization. Conclusion: G‐CSF increases the DPT, ERP and VFT and reduces the infarct size, thus stabilizing the myocardial electrophysiology, and preventing fatal arrhythmia during I/R. The protective mechanism could be via its effect in preventing cardiac mitochondrial dysfunction.     

Comparative pathomorphological study of contractile myocardium under conditions of increased left and right ventricular afterload

Structural changes in the myocardium under conditions of increased left and right ventricular afterload were studied using polarization microscopy and histological, histochemical, and stereological methods. Increased afterload not complicated by heart failure was characterized by low number of damaged cardiomyocytes (3.3–6.5%) and moderate structural changes in the ventricular myocardium (contractures of different severity). Increased afterload complicated by heart failure was characterized by high ratio of damaged cardiomyocytes (5.6–19.2%) and severe reversible (grade I and II contractures) and irreversible (grade III contractures and lump degradation of myofibrils) structural changes. Irreversible damage to most cardiomyocytes included plasmatic impregnation, which was most pronounced in the sub-endocardial layer of ventricles operating under conditions of increased afterload. Comparative study showed that increased left and right ventricular afterload induces similar pathomorphological changes in the contractile myocardium. Our results indicate that increased afterload to the right or left ventricle is accompanied by the development of stereotypical structural changes in the myocardium. Profound and severe disturbances can cause heart failure.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 12, pp. 693–697, December, 2004This revised version was published online in April 2005 with a corrected cover date.     

Pathomorphology of myocardial circulation: Comparative study in increased left or right ventricle afterload

Comparative study of pathomorphology of myocardial circulation under conditions of increased afterload of the left or right ventricles showed similar changes. All compartments of the coronary bed were plethoric, capillary blood stasis and perivascular edema, more pronounced in arterial vessels, were detected in both cases. These changes equally involved both ventricles and the ventricular septum. Significant differences consisted in local increase in the density of functioning capillaries. The increase was the maximum in hemodynamically overloaded ventricle and ventricular septum, presumably due to increase of their contractile activity. The density of functioning capillaries in the intact (vs. pressure overloaded) ventricle also increased, but to a lesser degree, which could be due to systemic neurohumoral effects. If increased afterload was complicated by the development of heart failure, circulatory disorders in the myocardium progressed. Significant increase in the density of functioning capillaries in all cardiac compartments indicated decreased vascular tone and exhaustion of coronary reserve. This was paralleled by a sharp arterial plethora in case of increased afterload of the left ventricle and sharp blood stasis in the microcirculatory bed in case of increased right ventricle afterload. Reduction of effective perfusion pressure in the presence of coronary dystonia can cause coronary insufficiency and myocardial ischemia in case of increased right ventricle afterload. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 352–356, March, 2008