心肌梗死后心室电重构的细胞和分子生物学机制

Arrhythmia is common in cardiovascular diseases, especially after myocardial infarction. This article reviews the electrophysiologic changes following myocardial infarction at different phases. Modulations of ion channel function that might contribute to electrical remodeling, such as cellular (autocrine/paracrine) factors and regulators of ion channel gene, are discussed. Unresolved problems in ventricular electrical remodeling after myocardial infarction are also considered.     

参松养心胶囊对糖尿病大鼠心室电生理特性及结构功能变化的影响

 目的：探讨参松养心胶囊（SSYX）对糖尿病（DM）大鼠心室电生理特性与结构功能变化的影响。方法：雄性SD大鼠45只,随机分为对照组（CTL组,n=15）、DM组（n=15）和SSYX组（n=15）。DM组和SSYX组采用一次性腹腔注射链脲佐菌素（60 mg/kg）制备糖尿病模型,CTL组则给予腹腔注射生理盐水（1 mL/kg）,72 h后检测血糖评价造模结果,将造模成功的动物纳入本研究。SSYX组连续6周给予SSYX灌胃（1 g·kg-1·d-1）治疗,DM组和CTL组则给予生理盐水灌胃（2 mL·kg-1·d-1）。动物完成药物治疗后,采用超声心动图检测心功能并记录II导联体表心电图;采用放射免疫法检测血浆的内皮素1（ET-1）水平;随后在整体心脏Langendorff灌流条件下行离体电生理研究,分别记录和测量左室前游离壁（LAF）心外膜单相动作电位（MAP）和有效不应期（VERP）,同时给予Burst快速电刺激用以进行室性心律失常（VA）的诱发;采用Masson染色对3组动物心肌纤维化程度进行评价。结果：与CTL组相比,DM组心功能下降（P<001）,而QT间期、VERP、动作电位时程、VA诱发率、心肌纤维化程度和血浆ET-1水平均增加（均P<001）;与DM组相比,SSYX组的心功能得到改善（均P<001）,且 QT间期、VERP、动作电位时程、VA诱发率、心肌纤维化程度和血浆ET-1水平均降低（均P<005）。结论：SSYX具有减轻DM大鼠心室电重构和结构重构及改善心功能的作用。     

Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction

Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-week-old Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 μg PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-β and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.     

Functional changes in left ventricular hypertrophy: diagnosis of impaired diastolic function in patients with hypertension

Summary Left ventricular hypertrophy is usually associated with impaired left ventricular diastolic function which can be characterised by an altered pressure volume relationship. Since diastolic flow velocities are closely related to the difference in pressure between the left atrium and left ventricle, parameters of diastolic function can be determined by Doppler echocardiography. However, the pressure difference is additionally influenced by factors which have no relation to left ventricular diastolic function. These include preload, afterload, inotropy, heart rate and left ventricular systolic function. Despite these limitations, Doppler echocardiography is a valuable tool to diagnose therapeutic effects on diastolic function in patients with left ventricular hypertrophy.     

Further evidence for the involvement of cardiac β-adrenergic receptors in right ventricle hypertrophy and ascites in broiler chickens

The present study was carried out to determine, first, the cardiac β -adrenergic receptor characteristics of broiler chick embryos exposed to two different CO 2 levels during the last stage of embryonic development, and second, the prophylactic effect of β 1 -adrenoceptor blocker on right ventricular hypertrophy in broiler chickens. High CO 2 embryos showed significantly higher haematocrit values, higher partial pressure of CO 2 levels and lower partial pressure of O 2 levels than those of normal CO 2 embryos. Exposure of chick embryos to high CO 2 levels reduced the binding capacity of myocardial β -adrenergic receptors compared with those embryos incubated at the normal CO 2 level. Atenolol-supplemented diet numerically reduced ascites incidence in broiler chickens (7%) compared with birds fed the control diet (15%). In conclusion, these data support the important role of the β -adrenergic receptor in the cardiovascular system for cardiac output, and secondary to pulmonary hypertension syndrome.     

The effect of cryoinjury on ventricular tachycardia in the swine right ventricle

This study was performed to assess the influence of the cryoinjury on the dynamics of wavefronts and to determine whether they can convert ventricular fibrillation (VF) to ventricular tachycardia (VT) in fibrillating right ventricular (RV) of swines using an optical mapping system. A cryoinjury with a diameter of 12 mm was created on the epicardium of perfused RV of swines (n = 6) and optical mapping were taken from baseline until 10 minutes after the cryoinjury. Out of 35 cryoinjuries, the images were possible to be interpreted in 32. The optical action potential could not be observed in either the cryoinjury or peri-injury sites at 1 and 3 minutes, was observed in only the cryoinjury site at 5 minutes, and recovered in both sites at 10 minutes. The cycle length of the tachycardia was 135.9 +/- 23.6 msec at baseline, 176.2 +/- 79.3 msec at 1 minute, 187.6 +/- 97.9 msec at 3 minutes, 185.5 +/- 19.2 msec at 5 minutes, and 152.1 +/- 64.1 msec at 10 minutes. The cycle lengths at 1, 3, and 5 minutes after the cryoinjury were significantly more prolonged than that at baseline (p = 0.001, p = 0.006, p = 0.016). After the cryoinjury, the VF changed to VT in 9 (28.0%), and terminated in 2 (6.3%). These changes were observed mainly within 5 minutes after cryoinjury. The cryoinjury had anti-fibrillatory effects on the tissue with VF. This phenomenon was related to a decreasing mass and stabilizing wavefronts.     

The effect of cold and dietary energy on right ventricular hypertrophy, right ventricular failure and ascites in meat-type chickens

Male progeny from two commercial sire strains, were fed on a high energy or low energy diet and kept at an environmental temperature of 23 C or 13 degrees C after day 22 to day 57. In the cold 42.4% of strain A and 29.6% of strain B died from right ventricular failure (RVF) and ascites secondary to pulmonary hypertension (PH) prior to day 57. Of the birds surviving to day 57, 9.4% (strain A) and 6.4% (strain B) had RVF and ascites. In the warm, 17.3% (A) and 7.4% (B) died from RVF and ascites before day 57 and 4.6% and 3.2%, respectively had ascites at day 57. Chickens on the high energy diet were significantly heavier at day 56 than those on the low energy diet, particularly those kept in the cold. However, chickens on the latter diet had better weight gain between days 42 and 56, again more marked in cold conditions. The higher metabolic rate elicited by cold would increase oxygen consumption and blood flow in these broilers which, because of their rapid growth, already had a high metabolic rate. The cause of PH was probably insufficient pulmonary vascular capillary capacity for the blood flow necessary to meet their metabolic oxygen requirement.     

The effect of increased sodium in the drinking water on right ventricular hypertrophy, right ventricular failure and ascites in broiler chickens

One hundred commercial male broiler chickens were grown to 27 days in four floor pens on a commercial diet containing 0.14% sodium (Na+). From day 6 each pen received different levels of sodium chloride (NaCl) in the drinking water; 0.0%, 0.15% (0.06% Na+), 0.3% (0.12% Na+) and 0.6% (0.24% Na+). Eight chicks from each group were killed at 13, 20 and 27 days and examined for right ventricular hypertrophy (RVH) and right ventricular failure (RVF). By day 27 as little as 0.06% added Na+ caused two cases of RVH and one case of RVF with ascites, typical of the ascites caused by RVF in commercial broilers. RVH, RVF and ascites developed earlier in broilers on higher levels of Na+.     

The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction

Regeneration of the damaged myocardium is one of the most challenging fronts in the field of tissue engineering due to the limited capacity of adult heart tissue to heal and to the mechanical and structural constraints of the cardiac tissue. In this study we demonstrate that an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties, improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted onto the infarcted myocardium in adult murine hearts immediately after ligation of left anterior descending artery and the physiological outcomes were monitored by echocardiography, and by hemodynamic and histological analyses four weeks post infarction. In comparison to infarcted hearts with no treatment, hearts bearing patches preserved contractility and significantly protected the cardiac tissue from injury at the anatomical and functional levels. This improvement was accompanied by attenuated left ventricular remodeling, diminished fibrosis, and formation of a network of interconnected blood vessels within the infarct. Histological and immunostaining confirmed integration of the patch with native cardiac cells including fibroblasts, smooth muscle cells, epicardial cells, and immature cardiomyocytes. In summary, an acellular biomaterial with specific biomechanical properties promotes the endogenous capacity of the infarcted myocardium to attenuate remodeling and improve heart function following myocardial infarction.     

心肌肥厚重塑的免疫机制研究进展

心血管疾病严重威胁人类健康,其继发的心肌肥厚和重塑是导致心脏功能逐渐恶化的关键因素.近年来,分子免疫学机制在心肌肥厚和重塑形成中的作用逐渐引起关注.研究多种细胞类型在心肌肥厚和重塑中的作用,如非心肌细胞,尤其是免疫细胞相互作用和炎症信号作用的机制,巨噬细胞、成纤维细胞和肾素-血管紧张素-醛固酮系统在心肌肥厚与重塑病理生理中的作用,对不同免疫细胞类型在心肌细胞肥大调控具有重要性以及潜在的治疗靶点.     

Aerobic exercise improves the inflammatory profile correlated with cardiac remodeling and function in chronic heart failure rats

OBJECTIVE:

The aim of the present study was to evaluate the effect of 8 weeks of aerobic exercise training on cardiac functioning and remodeling and on the plasma levels of inflammatory cytokines in chronic heart failure rats.

METHODS:

Wistar rats were subjected to myocardial infarction or sham surgery and assigned to 4 groups: chronic heart failure trained (n = 7), chronic heart failure sedentary (n = 6), sham trained (n = 8) and sham sedentary (n = 8). Four weeks after the surgical procedures, the rats were subjected to aerobic training in the form of treadmill running (50 min/day, 5 times per week, 16 m/min). At the end of 8 weeks, the rats were placed under anesthesia, the hemodynamic variables were recorded and blood samples were collected. Cardiac hypertrophy was evaluated using the left ventricular weight/body weight ratio, and the collagen volume fraction was assessed using histology.

RESULTS:

The chronic heart failure trained group showed a reduction in left ventricular end-diastolic pressure, a lower left ventricular weight/body weight ratio and a lower collagen volume fraction compared with the chronic heart failure sedentary group. In addition, exercise training reduced the plasma levels of TNF-α and IL-6 and increased the plasma level of IL-10.

CONCLUSION:

An 8-week aerobic exercise training program improved the inflammatory profile and cardiac function and attenuated cardiac remodeling in chronic heart failure rats.     

移植MMSCs改善大鼠实验性心肌梗死后心室重构

目的探讨骨髓间充质干细胞(MMSCs)移植对大鼠实验性心肌梗死(MI)后心功能及心室重构的影响。方法开胸结扎冠状动脉左前降支(LAD)制作MI动物模型,造模成功后12～14d经舌下静脉移植已转染增强型绿色荧光蛋白(pEGFP-C1)的MMSCs,分4及8周检测动物的血流动力学、左心及全心质量指数、微血管密度测定、双盲计数法测定胶原含量,荧光显微镜观察绿色荧光的表达。结果移植组心率(HR)较同期模型组显著下降,4周时血压无明显改变,8周时则显著增高。移植组左心质量指数和全心质量指数均较同期模型组显著降低。移植组的微血管密度较同期模型组明显增高。移植组的胶原含量较同期模型组显著降低。结论移植MMSCs可改善实验性MI大鼠心功能及心室重构。     

Echocardiographic assessment of right ventricular function in responders and non-responders to cardiac resynchronization therapy

Introduction

The aim of this study was to determine whether baseline right ventricular (RV) function assessed by standard echocardiography may indicate patients who will respond to cardiac resynchronization therapy (CRT).

Material and methods

The data of 57 patients (54 men, 95%), aged 66.4 ±8.7 years with heart failure (HF) having a CRT device implanted were collected. All patients had left ventricular ejection fraction (LVEF) ≤ 35% and QRS complex duration ≥ 120 ms. Echocardiographic examination with tissue Doppler imaging techniques and complex RV evaluation were performed at baseline and three months after CRT onset.

Results

Three months after CRT implantation, patients responding to CRT, defined as a reduction of left ventricle end-systolic volume (LVESV) of at least 10% (n = 34), compared to patients with a reduction of LVESV of less than 10% (n = 23), had at baseline a smaller right atrium diameter (47.85 ±11.33 mm vs. 52.65 ±8.69 mm; p = 0.028), higher TAPSE (14.56 ±2.57 mm vs. 13.04 ±2.93 mm; p = 0.030) and lower grade of tricuspid valve regurgitation (1.82 ±0.97 vs. 2.3 ±0.88; p = 0.033).

Conclusions

This study showed that there are differences in baseline right ventricular function between responders and non-responders to CRT. Yet in our study, none of the baseline RV parameters provided any value in identifying patients who would respond to CRT.     

罗格列酮对兔急性心肌梗死后心室重构及心功能的影响

目的 探讨罗格列酮(Ros)对兔急性心肌梗死(AMI)后心室重构和心功能的影响.方法 将30只日本大耳白兔随机分为:假手术(Sham)组,AMI模型组,Ros组,每组10只.永久性结扎冠状动脉左前降支中上1/3处制作AMI模型,术后6h Ros组给予Ros 3mg/(kg·d)灌胃,AMI组及sham龃给予等量蒸馏水灌...     

Changes in mass of the right ventricle and its RNA content during regression of hypertrophy

Noninbred male rats weighing 250–300 g were used. Adaptation to high-altitude hypoxia was produced by keeping the animals once a week for 5 h in a pressure chamber at an altitude of 6000 m. The degree of hypertrophy of the right ventricle and its RNA content were studied after 20 days of adaptation and also 2, 10, 20, and 40 days after the end of exposure to hypoxia. The mass of the right ventricle and its RNA concentration and content were significantly increased 20 days after the beginning of adaptation. After the end of exposure to hypoxia half of the increase in mass of the right ventricle was lost during the next 10 days and half of the increase in RNA during the next 2 days. Forty days after the end of exposure to hypoxia the mass of the right ventricle and its RNA content in the adapted animals were indistinguishable from those in the controls.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1421–1422, December, 1976.     

黄芪对大鼠心肌梗塞后左室功能及胶原改建的影响

目的：在实验性大鼠心肌梗塞模型上、观察黄芪对心梗后左室功能及胶原改建影响。方法：心梗后腹腔注射黄芪注２或６周，用放免法血浆、心肌血浆紧张素Ⅱ在浆醛固酮（ＡＬＤ）；动脉插管测定心功能；氯胺Ｔ法测定非梗塞区（含梗塞周边区）左室心肌羟腈酸的水平，免疫组织化学法测量非梗塞区左室心肌Ⅰ型及Ⅲ型胶原蛋白的比值。结果：与心肌梗塞对照组比较，黄芪可降低６周时的血浆、并梗塞区心肌ＡｎｇⅡ及血浆ＡＬＤ水平；２周及６周