基质金属蛋白酶参与左心室重构的机制探讨

目的 探讨基质金属蛋白酶家族（MMPs）MMP-2、3、9与心衰患者心肌重构的关系。方法 选择因二尖瓣关闭不全，心脏病接受二尖瓣置换术的CHF病人39例，正常对照38例（其中8例来自意外伤亡的器官捐献者）。彩色多普勒超声心动图检测心功能参数，免疫沉淀法检测心肌组织MMP-2、3、9。结果 瓣膜病所致心力衰竭病人心肌组织呈心肌重构的病理改变；心衰病人心肌组织蛋白表达较正常人高，且随心功能的恶化，MMP-2、3、9含量相对越高（P〈0．05或0．01）。结论 MMP-2、3、9表达量的增高与心肌重构的病理过程。是影响心衰患者心功能的重要因素之一。     

心衰患者心肌组织中钠氢交换体1 mRNA的表达与血清胶原的相关性研究

目的观察心衰患者心肌组织中钠氢交换体1（sodium-hydrogen exchanger 1,NHE1）的表达及其与血清胶原的相关性,探讨NHE1在心衰发生和发展中的作用及其与心肌纤维化的相互关系。方法设心衰组及正常对照组,心衰组按NYHA分级分成心功能Ⅰ级、Ⅱ级及Ⅲ级3个亚组。采用实时荧光定量聚合酶链反应（FQ-PCR）检测受试者心肌组织中NHE1 mRNA的表达水平,采用放射免疫分析法分别测定血清Ⅰ型前胶原羧基端肽Ⅰ（PⅠCP）和Ⅲ型前胶原氨基端肽（PⅢNP）含量。结果心衰组PⅠCP、PⅢNP含量较正常对照组明显升高,随着心功能的逐渐恶化,心衰组PⅠCP、PⅢNP含量呈上升趋势,各组间表达总体上有差异（P〈0.05或P〈0.01）,PⅠCP、PⅢNP含量与NHE1 mRNA的△Ct值呈显著负相关。结论心衰患者心肌组织中存在NHE1 mRNA的高水平表达,血清PⅠCP、PⅢNP含量显著增加,提示NHE1可能在心衰的发生和发展过程中起着重要作用。     

老年心功能不全患者窦性心率震荡的临床研究

目的：探讨老年心功能不全患者窦性心率震荡的临床意义。方法：筛选72例老年心功能不全患者及70例正常人，对他们f进行24hHolter监测，测定震荡初始值（TO）、震荡斜率值（TS）并对常规变量：性别、LVEF、TD、码进行分析，观察其室性早搏后实性心率震荡现象并分析多变量关系，预测其相对危险度。结果：T0（＋）组、TS（＋）组、TO（＋）TS（＋）组、TO（-）TS（-）组各组中，心功能不全组与正常组二者比较均有显著性差异（P〈0．05）。说明心功能不全组TO值、TS值的阳性率明显高于对照组。老年患者，LVEF值低、TO和TS两项指标均异常时发生心衰的相对危险度大。结论：TO、TS值的测定是对老年心功能不全患者的有效高危预测指标；     

肾素血管紧张素系统与心衰患者心肌重构的机制研究

目的 探讨不同程度充血性心力衰竭（CHF）病人血浆血管紧张素浓度与心功能的关系。方法 选择因二尖瓣狭窄伴关闭不全心脏病接受二尖瓣置换术的CHF病人39例，正常对照38例（其中8例来自意外伤亡的器官捐献者）。彩色多普勒超声心动图检测心功能参数，放免法（RIA）检测CHF患者血浆及心肌组织Ang含量。结果 瓣膜病所致心力衰竭病人心肌组织呈心肌重塑的病理改变。CHF患者血浆及心肌组织Ang浓度显著高于对照组，且随心功能恶化逐渐增加。结论 肾素血管紧张素系统（RAS）在心肌重构中起重要作用。     

COPD患者MMP-9和TIMP-1水平变化及其与IL-8和IL-2相关性研究

目的：观察慢性阻塞性肺疾病（COPD）急性加重期患者血清基质金属蛋白酶9（MMP-9）、金属蛋白酶组织抑制剂1（TIMP-1）、IL-2和IL-8含量变化。同时观察COPD患者血清MMP-9、TIMP-1与IL-2及IL-8含量的相关性。方法：选取AECOPD患者42例,健康对照者15例,采用双抗夹心ELISA法测定血清MMP-9、TIMP-1、IL-2及IL-8含量。结果：AECOPD患者血清MMP-9、TIMP-1及IL-8水平明显高于健康对照者,IL-2水平低于健康对照者,差异有统计学意义（P〈0.05）,AECOPD患者血清MMP-9、TIMP-1含量均与IL-8呈正相关,与IL-2呈负相关。结论：COPD患者血清MMP-9/TIMP-1失衡,导致肺组织降解与沉积紊乱,参与了肺气肿的发生发展。     

左心辅助对急性左心衰犬心肌c-fos mRNA的影响

目的：探讨自制气动左心辅助泵对辅助急性左心衰实验犬后c—fos mRNA表达的影响。方法：20只实验犬随机分为3组：辅助组（A组，n=9）、心衰组（B组，n=9）和对照组（C组，n=2）。A组：急性左心衰后行左心辅助循环；B组：心衰形成后不进行左心辅助；C组：开胸后未行处理。于术后6h将动物处死，用RT—PCR方法检测心肌组织c—fosmRNA的表达。结果：对照组无c—fosmRNA表达，辅助组心肌组织有少量c—fos mRNA表达，心衰组心肌组织c—fos mRNA表达较辅助组显著增加（P〈0．01）。结论：自制气动左心辅助泵抑制了心肌缺血后c—fos mRNA的表达，保护心肌细胞并抑制了继发性损害的发生，是左心辅助改善心衰可能的作用机理。     

慢性心力衰竭心肌胶原重塑及其与心功能关系

为比较正常和慢性心力衰竭（心衰）心肌胶原变化及其与心功能的关系，用羊冠状动脉内微球栓塞法，对11只羊造成慢性心衰。6个月后，行血液动力学测定并检测心脏胶原含量和类别。结果显示，与正常组比较，心衰组左心室（LV）胶原含量和Ⅰ/Ⅲ型胶原比值明显增高。LV胶原含量和LV射血分数、LV舒张末压、dP/dtmin、LV舒张末期内径、室间隔厚度明显相关。提示在这种心衰模型中，心肌胶原含量和I/III比值明显升高且与心功能下降有关。     

慢性心衰患者年龄与端粒及心肌胶原的相关性研究

目的 探讨衰老与慢性心衰心肌纤维化的相关性及其可能机制.方法 将100例心脏病患者分为非心衰(心功能Ⅰ级)组50例,心衰(心功能Ⅱ～Ⅳ级)组50例.采用RT-PCR法检测外周血白细胞中端粒长度,应用ELISA方法检测血清中PⅠ CP、PⅢNP的浓度,并行相关性分析.结果 (1)心衰组血清PⅠ CP、PⅢNP含量较非心衰组均明显增高(P＜0.05);血清中PⅠ CP、PⅢNP含量与心功能分级均呈显著正相关(P＜0.05).(2)心衰组端粒长度较非心衰组明显缩短(P＜0.01);端粒长度与心功能分级呈显著负相关(P＜0.05).(3)心衰组及非心衰组血清中PⅠCP、PⅢNP含量均与年龄呈显著正相关(P＜0.05);(4)两组端粒长度均与年龄呈显著负相关(P＜0.05).(5)心衰组端粒长度与血清PⅠ CP、PⅢNP浓度均呈显著负相关(P＜0.01).结论 血清PⅠCP、PⅢNP浓度及端粒的长度与心功能密切相关,增龄(衰老)是心肌胶原增加及端粒缩短的独立危险因素,在慢性心衰心肌纤维化的发生、发展中起重要作用.     

小剂量甲状腺素治疗重症心力衰竭疗效观察

目的：观察小剂量甲状腺素在重症充血性心力衰竭中的疗效。方法：将心功能Ⅲ级和Ⅳ级34例随机分成对照组和观察组，测定两组的甲状腺激素水平，观察组给予小剂量甲状腺素治疗，观察其疗效。结果：两组均有不同程度的T3（三碘甲腺原胺酸）、FT3（游离甲状腺胺酸）降低，rT3（反三碘甲腺原胺酸）升高，TSH（促甲状腺素）正常，Ⅳ级心功能者还伴有T4（甲状腺素）、FT4（游离甲状腺素）明显下降（P〈0．01）；观察组经治疗后显效率及总有效率均明显高于对照组（P〈0．01）；观察组治疗后各心功能指标均优于对照组（P〈0．05）。结论：重症心力衰竭多伴有甲状腺激素变化，小剂量补充甲状腺素能提高血中游离甲状腺素含量，对纠正重症心衰有效，且无明显不良反应。     

18F-FDG心肌PET显像检测存活心肌的临床评价

目的 评价＾１８Ｆ－脱氧葡萄糖（ＦＤＧ）ＰＥＴ心肌葡萄糖代谢与＾９９ｍＴｃ－甲氧基异腈（ＭＩＢＩ）心肌灌注显像相结合对存活心肌的诊断价值。方法 ９０例临床确认为陈旧性心肌梗塞（ＯＭＩ）患者，男８０例，女１０例，平均年龄５５．８±９．７岁。所有患者行心肌灌注显像和心肌代谢显像，均做超声心动图心功能测定，其中７６例做冠状动脉造影。血运重建术后，３６例复查超声心动图，测定心功能（Ａ组）；２４例复查心肌灌     

Nandrolone inhibits MMP-2 in the left ventricle of rats

The indiscriminate use of anabolic-androgenic steroids has been shown to induce left ventricular dysfunctions. The main objective of the present study was to investigate the effects of nandrolone decanoate on matrix metalloprotease (MMP-2) activity and protein level in the left ventricle (LV) of rats after 7 weeks of mechanical load exercise. Wistar rats were grouped into: sedentary (S); nandrolone decanoate-treated sedentary (AAS); trained without AAS (T) and trained and treated with AAS (AAST). Exercised groups performed a 7-weeks water-jumping program. Training significantly increased the MMP-2 activity by zymography and the protein level by Western blotting analysis. However, the AAS treatment abolished both the increase in MMP activity and protein level induced by exercise. These results suggest that AAS may impair cardiac tissue remodeling which may lead to the heart malfunction.     

Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury

PURPOSE: Remodeling of extracellular matrix (ECM) after lung damage depends on collagen degrading Matrix-Metallo-Proteinases (MMP) and their endogenous inhibitors (Tissue-Inhibitors of Metallo-Proteinases, TIMP). Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of radiation-induced lung fibrosis upon its effects on fibroblast proliferation and collagen synthesis. Lung cancer patients have often elevated TGF-beta1 plasma levels as a result of increased TGF-beta1 expression in their tumours. On this background, we investigated the effect of irradiation on the MMP/TIMP system in the lung tissue of normal and transgenic TGF-beta1 mice, in which TGF-beta1 is overexpressed in the liver resulting in high TGF-beta1 plasma levels. MATERIAL AND METHODS: Transgenic (TG) and wild-type (WT) mice underwent thoracic irradiation with 12 Gy or sham-irradiation. For each study group (TG 12 Gy; TG 0 Gy; WT 12 Gy; WT 0 Gy) 8 mice were sacrificed at 4 and 8 weeks after (sham-) irradiation. The TGF-beta1, TIMP-1/-2/-3 expression in the lung tissue was quantified by Western blot; the MMP-2 and MMP-9 activity was analysed by zymography. The cellular origin of the MMP and TIMP was localised by immunohistochemistry. RESULTS: Irradiation had no influence on the TIMP-1/-2/-3, but increased significantly the MMP-2 /-9 expression. In the lung tissue of TG mice the TIMP-1/-2/-3 expression was elevated, the MMP-9 activity was decreased. The immunhistochemical study showed that parenchymal and inflammatory cells express these MMP/TIMP. CONCLUSION: Our results provide evidence that the overexpression of MMP-2 and MMP-9 is involved in the inflammatory response of radiation-induced lung injury. MMP-2 and MMP-9 are known to degrade collagen IV of basement membranes, therefore affecting the structural integrity of lung tissue. In contrast, in lung tissue of TG mice the TIMP-1/-2/-3 expression was up-regulated and the MMP-9 activity was diminished, thereby decreasing possibly the ECM degradation leading to lung fibrosis.     

Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury

Purpose: Remodeling of extracellular matrix (ECM) after lung damage depends on collagen degrading Matrix-Metallo-Proteinases (MMP) and their endogenous inhibitors (Tissue-Inhibitors of Metallo-Proteinases, TIMP). Transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of radiation-induced lung fibrosis upon its effects on fibroblast proliferation and collagen synthesis. Lung cancer patients have often elevated TGF-β1 plasma levels as a result of increased TGF-β1 expression in their tumours. On this background, we investigated the effect of irradiation on the MMP/TIMP system in the lung tissue of normal and transgenic TGF-β1 mice, in which TGF-β1 is overexpressed in the liver resulting in high TGF-β1 plasma levels.

Material and methods: Transgenic (TG) and wild-type (WT) mice underwent thoracic irradiation with 12 Gy or sham-irradiation. For each study group (TG 12 Gy; TG 0 Gy; WT 12 Gy; WT 0 Gy) 8 mice were sacrificed at 4 and 8 weeks after (sham-) irradiation. The TGF-β1, TIMP-1/-2/-3 expression in the lung tissue was quantified by Western blot; the MMP-2 and MMP-9 activity was analysed by zymography. The cellular origin of the MMP and TIMP was localised by immunohistochemistry.

Results: Irradiation had no influence on the TIMP-1/-2/-3, but increased significantly the MMP-2 /-9 expression. In the lung tissue of TG mice the TIMP-1/-2/-3 expression was elevated, the MMP-9 activity was decreased. The immunhistochemical study showed that parenchymal and inflammatory cells express these MMP/TIMP.

Conclusion: Our results provide evidence that the overexpression of MMP-2 and MMP-9 is involved in the inflammatory response of radiation-induced lung injury. MMP-2 and MMP-9 are known to degrade collagen IV of basement membranes, therefore affecting the structural integrity of lung tissue. In contrast, in lung tissue of TG mice the TIMP-1/-2/-3 expression was up-regulated and the MMP-9 activity was diminished, thereby decreasing possibly the ECM degradation leading to lung fibrosis.     

Porcelain heart

Rheumatic heart disease (RHD) was the leading-cause of death in individual aged 5-20 years a century ago. Developments in diagnosis and treatment, decreased the incidence of RHD and dropped its mortality-rate to less than 10% since the 1960s. Despite the existence of proven preventive strategies in early detection and management of rheumatic fever (RF), RHD remained the most common cause of cardiovascular-mortality and morbidity in patients with RF. Previous studies have showed that Jones criteria may have insufficient support to diagnose patients with RF. Patients with subclinical, ongoing, and unrecognized episodes of RF may present late to medical attention with complication of RF such as indolent carditis. Recent studies revealed the superior role of echocardiography, as compared with clinical screening to diagnose subclinical RHD. While valvular involvement and ventricular dysfunction of RHD can be easily detected with echocardiography and magnetic resonance imaging (MRI), it remains problematic to determine the presence of whether there is myocardial-calcification after rheumatic heart carditis and if yes, how much extent it involves. The current case-report suggests the superior role of computed tomography angiography (CTA), as compared with echocardiography and MRI, to diagnose RHD in individuals without known history of RF. CTA with high spatial-resolution accurately evaluates tissue characterization and simultaneous assessment of the anatomy and function of heart and coronaries, and can precisely differentiate RHD from other cause of porcelain heart. The use of CTA in RHD screening provides the opportunity to initiate secondary antibiotic prophylaxis to prevent the poor outcome of rheumatic heart disease.     

糖尿病患者血浆hs-CRP、MMP-9浓度与心功能不全的相关性分析

目的:探讨血浆高敏C反应蛋白(hs-CRP)、基质金属蛋白酶-9(MMP-9)浓度与糖尿病合并心功能不全患者的相关性。方法:本研究选择单纯糖尿病患者30例(对照组)和合并心功能不全患者30例(观察组),彩超测定各指标,结合体表面积计算左心室质量指数(LVMI),采用放射免疫和酶联免疫法(ELISA)测定血浆hs–CRP和MMP-9浓度。结果:观察组hs-CRP、MMP-9水平与正常对照组均有统计学差异(P<0.05或<0.01)。观察组LVMI水平与对照组有统计学差异(P<0.05)。校正性别、年龄、血脂差异,发现血清hs-CRP和MMP-9呈正相关。结论:血管内皮功能失调是糖尿病病理过程的早期改变,血清MMP-9和hs-CRP可能在其心功能发生发展过程中起了重要作用。     

辛伐他汀对急性冠状动脉综合征患者血清MMP-1、MMP-3的作用

目的 探讨急性冠状动脉综合征（ACS）辛伐他汀与动脉粥样斑块稳定的可能机制。方法 选择稳定型心垃痛（SAP）患者30例作为对照。随机将ACS患者分成辛伐他汀治疗组（30例）及常规治疗组（30倒），比较各组患者血清MMP-1、MMP-3水平变化。结果 SAP、ACS、健康对照三组之间MMP-1、MMP-3水平比较差异有统计学意义，辛伐他汀治疗组与常规治疗组治疗后血清MMP-1、MMP-3水平相比差异有统计学意义。结论 辛伐他汀可降低ACS患者血清MMP-1、MMP-3水平，从而起到稳定动脉粥样硬化斑块的作用。     

Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodobenzylguanidine

Background  Carvedilol treatment reduces the mortality rate in patients with congestive heart failure. It is not known whether carvedilol treatment is effective in heart failure patients with substantial cardiac sympathetic nerve dysfunction. The goal of this study was to determine the effect of chronic carvedilol treatment in patients with cardiac sympathetic nerve dysfunction of varying severity. Methods and Results  In 22 congestive heart failure patients with idiopathic cardiomyopathy, sympathetic nerve function was assessed before and after 7.2 ± 2.7 months of carvedilol treatment with the use of iodine 123 metaiodobenzylguanidine (MIBG) imaging, radionuclide ventriculography, and transmyocardial norepinephrine sampling. Patients with relatively advanced impairment of cardiac sympathetic nerve function, as manifested by a baseline I-123 MIBG ratio lower than 1.40, had a statistically significant improvement in I-123 heartmediastinum ratio with carvedilol treatment, from 1.26 ± 0.12 to 1.39 ± 0.20 (P = .004). Of 10 patients with a baseline I-123 MIBG ratio lower than 1.40, 9 had an increase in the heart-mediastinum ratio with carvedilol treatment. Left ventricular ejection fraction increased from 25.4% ± 7.8% to 37.3% ± 14.7% (P <.001), with no difference between patients with relatively advanced versus relatively preserved cardiac sympathetic nerve function. Conclusions  Most patients with congestive heart failure show a favorable response in left ventricular function to carvedilol treatment, regardless of the baseline level of cardiac sympathetic nervous system function, as assessed by neuronal imaging with I-123 MIBG. Patients with relatively advanced impairment of baseline I-123 MIBG uptake are most likely to show evidence of improved cardiac sympathetic nervous system function in response to carvedilol therapy.(J Nucl Cardiol 2002;9:608-15.) Sponsored in part by the American Heart Association-Ohio Valley Affiliate (SW-97-12-S), the National Institutes of Health (SCOR No. 93-07-26-01), and the John R. Strauss Fund for Research and Education in Cardiac Imaging.     

Incremental prognostic implications of brain natriuretic peptide, cardiac sympathetic nerve innervation, and noncardiac disorders in patients with heart failure.

Plasma brain natriuretic peptide (BNP) level and cardiac autonomic function are closely related to prognosis in patients with heart failure. However, their correlation and incremental prognostic values in human heart failure are unclear. We sought to evaluate the correlation between BNP level and cardiac sympathetic innervation assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG) and the prognostic value of combined assessment of risk factors for mortality in patients with heart failure. METHODS: After conventional examinations and measurements of plasma BNP level and heart-to-mediastinum ratio (HMR) of cardiac (123)I-MIBG activity, 158 patients with heart failure were prospectively followed with an endpoint of cardiac death for 16 mo. RESULTS: Fifteen deaths due to pump failure and 2 sudden cardiac deaths were documented. Plasma BNP level correlated with HMR significantly but not so tightly (r = 0.330, P < 0.0001). Univariate analysis identified plasma BNP level, HMR, chronic renal dysfunction, diabetes mellitus, age, and use of nitrates as significant predictors of fatal pump failure, and multivariate Cox analysis showed that plasma BNP level was the most powerful predictor of cardiac death. Patients with both plasma BNP level of > or = 172 pg/mL and late HMR of < or =1.74 had a greater annual rate of fatal pump failure than did those without (17.5%/y vs. 0%-3.9%/y, respectively). The hazard ratio of plasma BNP level (7.2) or cardiac (123)I-MIBG activity (10.1) increased to 34.4 when both variables were used, and prevalence of fatal pump failure significantly increased from 22% to 62.5% when diabetes mellitus and chronic renal dysfunction were present with a higher plasma BNP level and low cardiac (123)I-MIBG activity. CONCLUSION: Plasma BNP level is a stronger predictor than other risk factors for mortality in heart failure patients and is statistically significantly, but roughly, related to cardiac sympathetic nerve innervation. Impaired cardiac sympathetic nerve innervation and the presence of diabetes mellitus and chronic renal dysfunction, however, improve risk stratification of patients with heart failure and increased plasma BNP concentration.     

Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure

Iodine-123-metaiodobenzylguanidine (123I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage. OBJECTIVE: The aim of the present study was to compare cardiac sympathetic nervous activity assessed by 123I-MIBG imaging with serum levels of H-FABP in patients with heart failure. METHODS: Fifty patients with chronic heart failure were studied. 123I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay. RESULTS: Heart to mediastinum (H/M) ratios of 123I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r = -0.296, p = 0.029) and BNP (r = -0.335, p = 0.0213). Myocardial washout rate of 123I-MIBG was also correlated with H-FABP (r = 0.469, p < 0.001), norepinephrine (r = 0.433, p = 0.005), and BNP (r = 0.465, p = 0.001). CONCLUSIONS: These data suggest that cardiac sympathetic nervous activation was associated with ongoing cardiomyocyte damage characterized by an elevated serum level of H-FABP in patients with heart failure. 123I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart.