大鼠左心室内膜超微结构年龄特征

目的探讨大鼠左心室内膜超微结构随年龄变化规律。方法取新生(9日龄)、青年(3月龄)、中年(11月龄)和老年(23月龄)Sprague-Dawley大鼠的左心室内膜组织,体积分数4%戊二醛磷酸缓冲液固定,制作透射电子显微镜(TEM)和扫描电子显微镜(SEM)样品,TEM下观察内皮细胞及内皮下胶原超微结构,SEM观察心肌内皮超微结构。结果随大鼠年龄增长,内皮细胞质膜变得薄而疏松,质膜小泡及突起逐渐减少;内皮下胶原从幼年到中年逐渐增多,排列方向一致;老年大鼠的胶原束排列紊乱松散,大鼠内皮细胞表面皱折增多,细胞核形态变长且排列趋于一致。结论随着年龄的增长,大鼠心内膜组织的超微结构发生明显变化,这与心脏功能的改变以及心脏疾病的发生相关。     

Chronic Amiodarone Reduces Transmural Dispersion of Repolarization in the Canine Heart

Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. In addition to its β-blocking properties, amiodarone is known lo block the sodium, potassium, and calcium channels in the heart. Its complex electropharmacology notwithstanding, the reasons for the high efficacy of the drug remain unclear. Also not well understood is the basis for the low incidence of proarrhythmia seen with amiodarone relative to other agents with Class III actions. The present study was designed to examine the effects of chronic amiodarone in epicardial, endocardial, and M cells of the canine left ventricle. Methods and Results: We used standard microelectrode techniques to record transmembrane activity from endocardial, epicardial, mid-myocardial, and transmural strips isolated from the canine left ventricle. Tissues were obtained from mongrel dogs receiving amiodarone orally (30 to 40 mg/kg per day) for 30 to 45 days or from untreated controls. Chronic amiodarone produced a greater prolongation of action potential duration in epicardium and endwardium, but less of an increase, or even a decrease at slow rates, in the M region, thereby reducing transmural dispersion of repolarization. In addition, chronic amiodarone therapy suppressed the ability of the I_kr, blocker, d-sotalol, to induce a marked dispersion of repolarization or early afterdepolarization activity. Conclusion: Our data demonstrate for the first time a direct effect of chronic amiodarone treatment to differentially alter the cellular electrophysiology of ventricular myocardium so as to produce an important decrease in transmural dispersion of repolarization, especially under conditions in which dispersion is exaggerated. These results may contribute to our understanding of the effectiveness of amiodarone in the treatment of life-threatening arrhythmias as well as to our understanding of the low incidence of proarrhythmia attending therapy with chronic amiodarone in comparison with other Class III agents.     

Endothelial control of vascular and myocardial function in heart failure

Summary The effect of vascular endothelium, endocardium, and coronary endothelium on vascular tone and myocardial contraction-relaxation sequence in heart failure is discussed. Vascular endothelium affects underlying vascular smooth muscle through paracrine secretion of relaxing and constricting factors. In heart failure, systemic vasoconstriction results not only from neuroendocrine activation, but also from disturbed local endothelial control of vascular tone because of impaired endothelial-dependent vasodilation and because of increased plasma concentration of endothelin. Experimental evidence obtained in isolated cardiac muscle strips established the influence of endocardial endothelium on the duration of myocardial contraction and on the onset of myocardial relaxation. By analogy to vascular endothelium, both diffusible agents that abbreviate (endothelial-derived relaxation factor-like substance) and those that prolong (endocardin) myocardial contraction have been shown to be released from the endocardium. Similar agents are released from the coronary endothelium and, because of the close proximity of capillaries and myocytes, could exert a major effect on myocardial performance. Endothelial dysfunction and concomitant lack of release of myocardial relaxant factors could explain left ventricular relaxation abnormalities observed in the cardiac allograft or in arterial hypertension. Since endothelial-derived relaxation factor or nitric oxide mediates the coronary reactive hyperemic response, a negative inotropic action of nitric oxide could contribute to left ventricular failure when left ventricular wall stress is elevated, as occurs after myocardial infarction in the noninfarcted zone and during left ventricular volume or pressure overload in the absence of adequate hypertrophy.     

A novel algorithm for determining endocardial VT exit site from 12-lead surface ECG characteristics in human, infarct-related ventricular tachycardia

Introduction: Characteristics of the 12-lead ECG during VT are used to guide initial placement of mapping catheters in endocardial ventricular tachycardia (VT) ablation. Previously constructed algorithms for guidance in human infarct-related VT are limited to patients known to have anterior or inferior infarcts only. We hypothesized that 12-lead ECG characteristics could be used to determine VT exit site in patients with all types of infarction of unknown location.
Methods and Results: From noncontact activation maps of 121 LV VT in 51 patients undergoing catheter ablation, VT exit sites were determined and correlated with ECG characteristics according to bundle branch block configuration, limb lead polarity and patterns of precordial R-wave transition. Eight ECG patterns were identified that accounted for 71% of all VT and gave a positive predictive value (PPV) ≥70% using the first two criteria. No correlation was found with patterns of R-wave transition. Using these criteria an algorithm was developed, which was then applied prospectively and blinded to a further 17 VT in 11 patients. Of the 15 VT (88%) to which the algorithm predicted an exit site location (with a PPV ≥70%), 14 VT (93%) were correctly predicted by the algorithm.
Conclusion: This algorithm can be used to predict endocardial LV VT exit site location in patients undergoing catheter ablation of VT without knowledge of or reference to infarct location, and can be applied to patients with posterior and/or multiple sites of infarction.     

Acellular Endocardium as a Novel Biomaterial for the Intima of Tissue‐Engineered Small‐Caliber Vascular Grafts

We aimed to investigate whether acellular endocardium can be used as a useful biomaterial for the intima of engineered small‐caliber vascular grafts. Fresh endocardium was harvested from the swine left atrium and was decellularized by digestion with the decellularization solution of Triton X‐100 and SDS containing DNase I and RNase A. Surface morphological characteristics and Young's modulus were evaluated. To analyze the effect of mechanical characteristics on cell adhesion, the decellularized endocardium was stiffened with 2.5% glutaraldehyde. Small‐caliber vascular grafts were constructed using decellularized endocardium treated with or without glutaraldehyde as the intima. CD34+ cells were seeded onto the luminal surface of the vascular grafts and linked to bioreactors that simulate a pulsatile blood stream. Acellular endocardium had distinct surface morphological characteristics, which were quite different from those of other materials. The compliance of acellular endocardium was higher than that of other materials tested by Young's modulus. CD34+ cells formed a monolayer structure and adhered to the inner face of the acellular endocardium. The glutaraldehyde treatment stiffened the acellular endocardium but had little impact on the surface morphological characteristics or static adhesiveness of the cells. Data from the bioreactor study showed that the detachment of the cells from the surface of glutaraldehyde‐treated acellular endocardium increased dramatically when the pressure was equal or higher than 40 mm Hg, while the cells on the untreated acellular endocardium remained well and formed confluent monolayers and tight junctions under the same pressure. Acellular endocardium has distinct structures and mechanical characteristics that are beneficial for CD34+ cell adhesion and retention under dynamic fluid perfusion. Thus, it can be used as a useful biomaterial for the construction of the intima of engineered small‐caliber vascular grafts.     

Intercellular gaps in the early development of chick mural endocardium

Summary Embryonic chick hearts stages 15 to 21 according to the Hamburger-Hamilton series (1951) were subjected to TEM and light-microscopical examination to investigate ventricular mural endocardium during early trabeculation. Serial sectioning of consecutively-aged embryos indicated an invagination of the endocardial layer which lines the intertrabecular and intermuscular spaces. During the proceeding development, frequently occurring approaches and contacts between mural endocardium and myocardium could be observed. At all stages examined, the cardiac jelly appeared as an acellular, at particular sites very attenuated matrix. The intercellular gaps of the endocardium could not be correlated to the invagination and the endothelialization of the intertrabecular spaces.     

Morphological changes in endocardium subjected to global ischaemia

Summary To provide insight into the effects of severe ischaemia on endocardium, the sequence of morphological changes which develop in the endocardium of the isolated rat heart subjected to 0–12 hours of global ischaemia at 37°C was examined. A progression of changes occurred. Following one or more hours of ischaemia crater-like depressions and blebs appeared on the luminal surfaces of ventricular endothelial cells, with margination and clumping of nuclear chromatin, loss of glycogen granules, swelling of mitochondria, and the development of subendothelial membrane-bound dilatations of myocytes. Following two or more hours of ischaemia there was progressive separation of endothelial cells along their intercellular boundaries and desquamation of an increasing proportion of these cells. In regions of desquamation the surface was initially smooth due to persistence of the lamina densa of the basal lamina, but after longer periods of ischaemia the surface became rough with exposure first of the subendothelial connective tissue fibres (4 hours) and eventually of cardiac muscle cells (12 hours).     

心内膜三维重建及系统导航定位精度的基础研究

目的 基于低频电场方式对右心室进行三维重构,并对系统导航定位精度进行验证. 方法在实验动物猪体表粘贴三对皮肤电极,由此产生经胸空间正交的低频交流电场覆盖心脏区域,以普通导管电极在心腔内探测电场数据,对右心室心内膜进行三维重构,然后在重构模型的基础上,通过起搏右心室的方法对系统的导航定位精度进行验证. 结果 10例重构的右心室心内膜模型虽然存在变形.但结构相似,不影响导航定位.右心室起搏心电图显示即刻复位符合率100%,3h后复位符合率60%. 结论本方法重建右心室三维模型存在一定程度的形变,但导航定位精度高,即刻重复性好.     

心脏移植术后急性排异反应的监测

目的 总结原位心脏移植术后急性排异反应的监测。方法 2000－01／2002－04施行11例原位心脏移植手术，结合临床表现、心电图、超声心动图、化验检查及心内膜活栓等检查，对心脏移植术后急性排异反应的监测进行分析。结果 采用临床症状＋心电图＋超声心电图＋心肌血清学检测综合判断有6次急性排异反应，行心内膜活检证实Ⅰb级2次，Ⅲa级3次；术后常规行心内膜活检21次，仅发现急性排异反应Ⅰa或Ⅰb级5次。结论 急性排异反应是关系到心脏移植术后患者康复及愈后的重要因素，因此要及时、有效地进行监测；心内膜心肌活检是诊断急性排异反应敏感可靠的方法，但为有创性检查，有一定的并发症风险，其他多项无创性检查可作辅助指标，因此急性排异反应监测应把无创性检查与心内膜心肌活检有机地结合起来。     

Diagnosis of cardiac thrombosis in patients with atrial fibrillation in the absence of macroscopically visible thrombi

Summary Cardiac thrombosis due to atrial fibrillation (AF) has been recognized as the most common cause of cerebral embolism. However, sometimes no macroscopic thrombus is found at autopsy in the heart of a victim of this type of cerebral embolism. We investigated morphological changes in the left atrial endocardium of 31 patients (including 21 cases with AF) who had died of cerebral embolism. Rough endocardium (RE) seen macroscopically provided evidence for the existence of atrial thrombosis. The RE that appeared in AF cases was due to a granular and wrinkled appearance of the endocardium associated with oedematous and fibrous thickening. Fibrin-thread deposits were also always distinguishable. Mural thrombi and oedema with neutrophil infiltration in the subendocardium could be seen under the microscope. Small areas of endothelial denudation and thrombotic aggregations were commonly observed by scanning electron microscopy (SEM). These SEM lesions were significantly more frequent in cases with AF than in controls (P< 0.001). The diagnostic success rate for atrial thrombosis among cases with AF increased from 33.3% to 81% when thrombi proven by histological investigation of the areas with RE were added. Left atrial RE may be an anatomically relevant finding for the existence of atrial thrombosis with AF, when the thrombosis cannot be detected upon gross observation at autopsy.