TGF-β1与慢性心力衰竭大鼠心肌肥厚的关系

目的 探讨慢性心力衰竭心肌组织转化生长因子-β1(TGF-β1)的表达及意义.方法 采用肾上腹主动脉缩窄法制作雄性Wistar大鼠慢性心衰模型,随机分为心衰1 d组,心衰7 d组,心衰14 d组,另取假手术组作为对照.观察和比较成模后心衰各组和假手术组血流动力学参数及左心室肌重量指数(LVMI),免疫组化法对TGF-β1在各组的左室心肌的分布及表达进行半定量分析,用RT-PCR法测定TGF-β1mRNA在各组左室心肌的表达水平.结果 心衰模型各组TGF-β1的蛋白及mRNA均高于假手术组(P<0.01),且随着心力衰竭程度的加重而表达增多.结论 TGF-β1可能参与了大鼠压力负荷性心肌肥厚的发生和发展,其水平的高低与慢性心力衰竭的严重程度密切相关.     

NF-κB、TGF-β1在糖尿病大鼠心肌及主动脉中的表达

目的:探讨链脲佐菌素(STZ)诱导的糖尿病(DM)大鼠心肌及主动脉核转录因子-κB(NF-κB)、转化生长因子-β1(TGF-β1)的表达。方法:用HE及MASSON染色观察DM大鼠心肌及主动脉的病理改变,用免疫组化的方法检测上述免疫因子的表达。结果:DM大鼠心肌、主动脉NF-κB、TGF-β1表达均明显高于正常对照组(CON),差异有统计学意义(P0.01)。结论:NF-κB和TGF-β1在DM心血管并发症的发生发展机制中起重要作用。     

α1受体阻断剂对慢性心力衰竭大鼠心肌转化生长因子β1表达的影响

目的评价α1受体阻断剂(特拉唑嗪)对慢性心力衰竭(CHF)大鼠心肌转化生长因子β1(TGF-β1)表达水平的影响。方法选30只雄性Wistar大鼠,随机分为正常对照组(n=6)和模型组(n=24)。模型组应用阿霉素腹腔注射的方法制作CHF模型,并随机分成特拉唑嗪组(n=12)和安慰剂组(n=12)。特拉唑嗪组在造模第5周接受特拉唑嗪灌胃治疗,0.4mg·kg-1.d-1,安慰剂组用淀粉代替特拉唑嗪,疗程6w;第10周末处死所有大鼠。RT-PCR和免疫组化染色方法评价各组大鼠左室心肌TGF-β1表达水平。结果安慰剂组大鼠心肌TGF-β1mRNA和蛋白表达水平比对照组明显升高(P<0.01);特拉唑嗪组心肌TGF-β1mRNA和蛋白表达水平较对照组升高值明显低于安慰剂组(P<0.05)。结论CHF大鼠心肌TGF-β1表达水平明显升高;特拉唑嗪治疗能够阻止CHF大鼠心肌TGF-β1升高,有助于改善CHF大鼠心肌重构。     

心复康口服液对心力衰竭大鼠心肌肌酸、牛磺酸的影响

目的研究中药复方制剂心复康口服液对压力负荷型充血性心力衰竭大鼠心肌组织肌酸、牛磺酸水平的影响机制。方法将75只Wistar大鼠随机分为假手术组(SH)、腹主动脉缩窄模型组(CAA)、心复康口服液治疗组(XFK),每组25只。建立慢性压力负荷型心力衰竭大鼠模型,分别于药物干预6、12 w时检测各组大鼠心功能参数、心肌组织肌酸、牛磺酸的含量。结果①造模6、12 w后CAA组大鼠心功能明显降低,左室重量指数(LVMI)、左室舒张期末压(LVEDP)显著升高,左心室内压上升、下降的最大变化速率(±dp/dtmax)显著下降。XFK组大鼠心功能各项指标较模型组明显改善(P<0.01);与6 w比较,12 w时LVMI、LVEDP下降及+dp/dtmax升高显著(P<0.05,P<0.01),而-dp/dtmax则无显著性差异。②与SH组相比,造模后第6周,CAA组大鼠心肌肌酸、牛磺酸水平显著降低(P<0.01);造模后12 w时,上述改变更加显著(P<0.01)。与CAA组相比,造模后6 w起,XFK组大鼠心肌肌酸、牛磺酸水平不通程度升高(P<0.05,P<0.01);于12 w时,肌酸、牛磺酸水平则显著升高(P<0....     

风湿性心脏病患者致心力衰竭心肌组织中IL-1β TGF-β1和NF-κB/p65的表达及意义

目的:研究风湿性心脏病(风心病)致心力衰竭(心衰)患者心肌组织中白细胞介素-1β(IL-1β)、转化生长因子β1(TGF-β1)和核转录因子κB/p65(NF-κB/p65)的表达及其临床病理意义。方法:18例风心病(实验组)和10例正常人(对照组)左心室心肌组织,经4%甲醛固定后常规制作石蜡包埋切片,应用EnvisionTM免疫组化法检测IL-1β、TGF-β1和NF-κB/p65的表达。结果:风心病NYHA分级Ⅲ级或Ⅳ级心衰患者的IL-1β、TGF-β1和NF-κB/p65的表达阳性率及其评分明显高于NYHAⅠ级(P<0.05);实验组(包括pAF组和cAF组)的IL-1β、TGF-β1和NF-κB/p65的表达阳性率及其评分明显高于对照组(RSR组)(P<0.05);IL-1β、TGF-β1和NF-κB/p65的表达评分互相均存在密切正相关(P<0.05),且与左心室射血分数呈负相关,与左心室舒张末期直径呈正相关。结论:IL-1β、TGF-β1和NF-κB/p65在风心病心衰、心室重构的发生、发展中起着重要的促进作用。     

葛根素对心肌纤维化模型大鼠左室心肌组织中转化生长因子β_1和结缔组织生长因子表达的影响

目的:研究葛根素对心肌纤维化模型大鼠左室心肌组织中转化生长因子β1(TGF-β1)和结缔组织生长因子(CTGF)表达的影响。方法:采用异丙肾上腺素(5mg·kg-1.d-1×10d)皮下注射诱导大鼠心肌纤维化,给予葛根素(100mg·kg-1.d-1)干预,实验共8周。32只雄性SD大鼠随机分成4组:模型组,空白对照组,葛根素早期干预组,葛根素后期干预组;每组于实验末,计算左室质量指数,取左室心肌组织进行VG染色、免疫组化染色,分别测算胶原容积积分(CVF)、CTGF蛋白和TGF-β1蛋白含量,取左室游离壁心肌组织检测羟脯氨酸浓度和运用RT-PCR半定量分析CTGFmRNA和TGF-β1mRNA水平。结果:葛根素减少模型组大鼠左室质量指数、左室心肌组织CVF及羟脯氨酸浓度(P0.01),模型组大鼠左室心肌组织CTGF和TGF-β1的过度表达(P0.05)。相关分析显示4组大鼠的左室心肌组织CTGF蛋白含量与左室心肌组织CVF和羟脯氨酸浓度呈正相关(P0.05)。结论:葛根素减少心肌纤维化大鼠的左室心肌间质胶原沉积,减轻和延缓大鼠心肌纤维化,这种作用机制可能是通过抑制左室心肌组织中CTGF、TGF-β1的过度表达来实现。     

黄芩茎叶总黄酮灌胃对原发性高血压大鼠心肌重构及心肌组织NF-κB表达的影响

目的 观察不同剂量黄芩茎叶总黄酮对原发性高血压大鼠心肌重构的影响,并探讨其机制.方法 将50只原发性高血压大鼠随机分为高血压组、贝那普利组及低、中、高剂量黄芩组,每组各10只,另取10只普通Wistar大鼠作为对照组.贝那普利组及低、中、高剂量黄芩组分别给予每日5.0 mg/kg贝那普利及17.5、35.0、70.0 ...     

核转录因子-κB对氧化低密度脂蛋白诱导大鼠系膜细胞转化生长因子β1转录的调控

氧化低密度脂蛋白 (Ox LDL)是肾脏病发生发展中的重要因素。Ox LDL与细胞膜上的特异或非特异性受体结合而沉积于肾脏固有细胞内 ,促使其释放各种因子 ,最终引起肾小球细胞增生和细胞外基质沉积 ,但机制尚未明了。核转录因子 (NF κB) ,能与多种细胞因子、生长因子、化学趋化因子以及细胞外基质基因的启动子上的特异位点结合 ,启动其转录 ,在免疫炎症反应、抗凋亡和肿瘤发生中起着重要作用。Ox LDL激活NF κB对肾脏细胞影响的研究目前未见报道。我院采用SD大鼠肾脏系膜细胞(MC)为研究对象 ,观察Ox LDL对MCNF κB结合活性的影响 …     

抑制核因子κB对缺血再灌注大鼠心肌组织的保护作用

目的探讨丹参注射液对心肌组织的保护作用及其抑制NF-κB活化的可能机制。方法通过观察NF-κB抑制剂PDTC和丹参注射液处理的缺血再灌注（I/R）大鼠心肌,测定心肌组织MDA、MPO、SOD、NF-κB及ICAM-1、TGFβ1蛋白表达。结果心肌匀浆MDA含量、MPO活力明显高于对照组（P〈0.01）,SOD活性显著低于对照组（P〈0.01）;PDTC和丹参注射液组,MDA含量、MPO活性较I/R组明显减少（P〈0.01）,SOD较I/R组明显恢复（P〈0.01）。I/R组心肌细胞中NF-κBp65与ICAM-1蛋白表达信号显著增强,TGFβ1表达信号减低;在PDTC和丹参注射液组,NF-κBp65与ICAM-1表达水平较IR组明显降低,而TGFβ1呈相反变化。结论丹参注射液能增加I/R大鼠心肌SOD活性,减少脂质过氧化物MDA产生。减弱心肌MPO活力,减轻中性粒细胞对心肌细胞的浸润损害,抑制NF-κB的活化,保护I/R大鼠心肌组织。     

银杏叶提取物对大鼠肝组织TGF—β1mRNA表达及胶原沉积的影响

目的：研究银杏叶提取物（GbE)对CCl4大鼠肝组织TGF－β1mRNA表达及胶原沉积的影响。方法：Wistar大鼠40只随机分成正常组10只。四氯化碳（CCl4)组15只和GbE组（CCl4 GbE)组15只。12W后,观察各组大鼠肝纤维化程度;逆转录PCR法测定TGFβ1mRNA表达;测定肝组织丙二醛（MDA）及血浆血小板活化因子（PAF）含量。结果：CCl4组8只大鼠肝脏内形成假小叶,GbE组中3只大鼠肝脏有假小叶形成。GbE组大鼠TGFβ1mRNA表达、肝组织中MDA及血浆PAF含量明显低于CCl4组（P＜0．05）。结论：GbE能下调CCl4大鼠肝组织TGFβ1mRNA表达并抑制胶原沉积。     

曲美他嗪对慢性心力衰竭大鼠心肌能量代谢及超微结构的影响

目的研究曲美他嗪对异丙肾上腺素诱导的慢性心力衰竭大鼠心肌能量代谢和超微结构的影响。方法72只雄性SD大鼠随机分为对照组(14只)和模型组(58只),模型制备采用皮下多点注射异丙肾上腺素法,4周后模型组大鼠死亡12只,再将存活的46只模型组大鼠随机分为未治疗组(M组,16只)、曲美他嗪治疗组(T组,15只)和培哚普利治疗组(P组,15只)。治疗5周后行二维心脏超声检查和病理形态学观察,并测定心肌组织能量代谢相关指标。结果与M组比较,T组大鼠LVEF、左心室短轴缩短率均提高;光镜和电镜下观察T组和P组心肌损伤程度较M组明显减轻。T组与P组大鼠心肌二磷酸腺苷(ADP)、一磷酸腺苷、ATP/ADP和总腺苷含量与对照组比较差异无统计学意义(P>0.05)。T组大鼠心肌肌浆网Ca2+-ATPase活性与对照组和P组比较差异无统计学意义。结论曲美他嗪能够改善心力衰竭大鼠心肌能量代谢、病理和超微结构,并且有改善大鼠心功能的趋势。     

非诺贝特对慢性心力衰竭大鼠心肌能量代谢和心室重构的影响

目的研究非诺贝特对慢性心力衰竭(CHF)大鼠心肌能量代谢和心室重构的影响。方法健康雄性Wistar大鼠随机选为假手术组18只;采用腹主动脉缩窄术制备CHF、并成功存活的38只再随机分为对照组20只、非诺贝特组18只[非诺贝特150 mg/(kg·d)],干预10周。计算左心室心肌重构指数、胶原容积分数(CVF)、心肌线粒体损伤程度分级用Flameng评分,免疫印迹法测过氧化物酶体增殖物激活受体α(PPARα)、中链酰基辅酶A脱氢酶(MCAD)、肌型肉碱棕榈酰转移酶1(MCPT 1)蛋白表达,RT-PCR测PPARα、MCAD和MCPT-1mRNA表达。结果与假手术组比较,对照组及非诺贝特组左心室心肌重构指数、CVF和Flameng评分均升高(P<0.05);非诺贝特组左心室心肌重构指数高于对照组、CVF和Flameng评分低于对照组(P<0.05);与假手术组比较,对照组、非诺贝特组心肌PPARα、MCPT-1、MCAD蛋白和基因表达均下调(P<0.05);非诺贝特组表达较对照组上调(P<0.05)。结论非诺贝特通过增强脂肪酸氧化,减轻线粒体损伤,改善心室重构,减轻心肌纤维化。     

Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats

BackgroundThis study aimed to explore the effects of Kangdaxin oral liquid on myocardial fibrosis in heart failure with preserved ejection fraction (HFpEF) rats.MethodsA total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups Sham operation group (Sham), HFpEF group (HFpEF), and HFpEF with drug intervention group (HFpEF + I). Rats in HFpEF + I group were given Kangdaxin oral liquid at a dose of 2.7 mL/(kg·d). After modeling or treatment, the value of E/A and E/e'' in each group of rats were measured by echocardiography. The N-terminal pro b-type natriuretic peptide (NT-proBNP) level was determined by enzyme-linked immunosorbent assay (ELISA). Heart weight/body mass index (Hw/W) and left ventricular weight/body mass index (LVw/W) were calculated after the rats were sacrificed; the transforming growth factor-β1 (TGF-β1) protein expression level in cardiac tissue was detected by western blot.ResultsCompared with sham group, the values of diastolic function item (E/A) and mitral annular early diastolic velocity (E/e'') in HFpEF group were significantly decreased, and the level of NT-proBNP was significantly increased (P<0.05). Compared with HFpEF group, the value of E/A and E/e'' in HF + I group were significantly increased, and the level of NT-proBNP was significantly decreased (P<0.05). Compared with sham group, the expression of TGF-β1 protein in heart tissue of HFpEF group were significantly increased (P<0.05). Compared with HFpEF group, the expression of TGF-β1 protein in HFpEF + I group were significantly decreased (P<0.05).ConclusionsKangdaxin oral liquid has protective effect on heart in HFpEF rats, which can reduce the protein expression of TGF-β1 in the heart tissue of HFpEF rats. This may be a possible mechanism to inhibit myocardial fibrosis and improve cardiac diastolic function.     

吡格列酮对老年自发性高血压大鼠心肌纤维化及胶原代谢的影响

目的探讨吡格列酮对老年自发性高血压大鼠(SHRs)心肌纤维化及胶原代谢的影响和可能机制。方法 12月龄SHRs分为吡格列酮组和SHR组,同月龄WKY鼠为对照组。观察大鼠体重及尾动脉血压、测定左室重量指数(LVI)、心肌胶原定性分析、测定心肌羟脯氨酸含量、Westen印迹法检测心肌基质金属蛋白酶(MMP)-1、MMP抑制物(TIMP)-1蛋白表达、测定心肌活性氧(ROS)和超氧化物歧化酶(SOD)水平并观察心肌过氧化物酶体增殖物激活受体(PPAR)γmRNA表达和组织定位。结果与对照组相比,SHR组血压、胶原容积积分、血管周围胶原面积和左室心肌组织羟脯氨酸浓度明显升高,吡格列酮组能改善心肌纤维化;SHR组MMP-1/TIMP-1显著降低,吡格列酮组MMP-1/TIMP-1水平显著升高,PPARγ表达增多,心肌ROS浓度显著下降(P0.05)。结论吡格列酮通过调节MMPs/TIMP平衡促进胶原降解,抑制胶原的沉积,抑制心肌纤维化,机制可能是通过激活PPARγ和抑制ROS的形成。     

Elevated myocardial Akt signaling ameliorates doxorubicin-induced congestive heart failure and promotes heart growth

Doxorubicin is a chemotherapeutic agent that can induce cardiotoxicity and congestive heart failure (CHF). In this study we tested whether intracoronary Akt1 gene delivery could inhibit doxorubicin-induced CHF. Saline or a replication defective adenoviral vector expressing constitutively-active Akt1 (myrAkt) or beta-galactosidase (betagal) was delivered to the myocardium of 8 week old rats one day prior to initiating doxorubicin administration. In animals receiving saline or betagal, doxorubicin resulted in significant decreases in cardiac function and retarded post-natal heart growth at the 5 weeks time point. In contrast, transduction of myrAkt protected hearts against doxorubicin-induced decreases in fractional shortening and cardiac index, and improved left ventricular function at 5 weeks time point. Delivery of myrAkt also reversed the doxorubicin-induced reduction in post-natal heart growth and diminished lung edema. These data show that myocardial Akt can inhibit doxorubicin-induced reductions in cardiac function and growth, suggesting that manipulation of this signaling pathway may have utility for the treatment of congestive heart failure.     

Oleylethanolamide activates Ras-Erk pathway and improves myocardial function in doxorubicin-induced heart failure

Oleylethanolamide (OEA) is a natural fatty acid ethanolamide produced in the heart, but its biological actions in myocardium have not yet been defined. This study was carried out to determine whether OEA could be used to prevent the development of heart failure or improve evolving heart failure. We studied in vivo and in vitro actions of OEA in cardiac muscle. In an animal model of doxorubicin cardiomyopathy, OEA showed robust effects and attenuated the progression of systolic/diastolic dysfunction and ventricular remodeling. During evolving doxorubicin cardiomyopathy, a therapeutic course of OEA treatment partially restored myocardial function. The preventive and therapeutic effects of OEA were associated with significant improvement of survival. To investigate the mechanism of OEA action in cardiac muscle, we have carried out in vitro experiments in cultured cardiomyocytes. The results showed that OEA, through activation of Ras-Raf-1-Mek-Erk signaling, inhibited doxorubicin-induced apoptosis. Additional experiments showed that OEA activation of the Erk pathway involved activation of Neu/ErbB2 receptor, which suggests OEA actions in cardiac muscle might require activation of Neu/ErbB2. In summary, OEA improved ventricular remodeling and augmented cardiac function in doxorubicin cardiomyopathy, possibly involving activation of Neu/ErbB2 and Ras-Erk signaling. These findings suggest OEA is a novel cardioprotective compound that may be used to develop new strategies for the management of cardiomyopathy.     

缬沙坦合用安体舒通对急性心肌梗死伴室壁瘤患者血运重建后的血清胶原水平和心功能的影响

目的:研究缬沙坦及合用安体舒通对经再灌注治疗的急性心肌梗死患者血清胶原水平和心功能的影响。方法:首次急性前壁心肌梗死伴室壁瘤患者70例,随机分为缬沙坦组、合用药组(缬沙坦合用安体舒通),在治疗后1周、2周、12周测定血清Ⅰ型前胶原羧基末端肽(PⅠCP)和Ⅲ型前胶原氨基末端肽(PⅢNP)浓度;并在治疗后2周、12周进行二维超声心动图检查。结果:12周时合用药组血清PⅢNP、血清PⅠCP较缬沙坦组明显降低(P0.05)。合用药组的舒张末期容积指数、收缩末期容积指数、局部室壁运动指数、左室射血分数及左室质量指数较缬沙坦组明显改善(P0.05)。结论:缬沙坦能够阻抑急性心肌梗死伴室壁瘤患者的胶原合成,改善心室收缩和舒张功能;合用药组的作用优于单用缬沙坦,显著改善心室收缩和舒张功能。     

Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

Background Growth differentiation factor (GDF)-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure (HF). HF frequently develops after myocardial infarction (MI), contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF. Methods The study consists of a cohort of 179 patients, including stable angina pectoris patients (AP group, n = 50), old MI patients without HF (OMI group, n = 56), old MI patients with HF (OMI-HF group, n = 38) and normal Control group (n = 35). Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide (PINP), type I collagen carboxy-terminal peptide (ICTP), precollagen III N-terminal peptide (PIIINP) and GDF-15 were measured using an enzyme-linked inmunosorbent assay. Results The plasma GDF-15 level was higher in OMI-HF group (1373.4 ± 275.4 ng/L) than OMI group (1036.1 ± 248.6 ng/L), AP group (784.6 ± 222.4 ng/L) and Control group (483.8 ± 186.4 ng/L) (P < 0.001). The indicators of collagen turnover (ICTP, PINP, PIIINP) all increased in the OMI-HF group compared with Control group (3.03 ± 1.02 μg/L vs. 2.08 ± 0.95 μg/L, 22.2 ± 6.6 μg/L vs. 16.7 ± 5.1 μg/L and 13.2 ± 7.9 μg/L vs. 6.4 ± 2.1 μg/L, respectively; P < 0.01). GDF-15 positively correlated with ICTP and PIIINP (r = 0.302, P < 0.001 and r = 0.206, P = 0.006, respectively). GDF-15 positively correlated to the echocardiographic diastolic indicators E/Em and left atrial pressure (r = 0.349 and r = 0.358, respectively; P < 0.01), and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities (Sm) (r = -0.623 and r = -0.365, respectively; P < 0.01). Conclusion Plasma GDF-15 is associated with the indicators of type I and III collagen turnover.     

雄激素对扩张型心肌病慢性心力衰竭雄性大鼠心肌细胞凋亡的影响

目的:探讨雄激素对扩张型心肌病慢性心力衰竭雄性大鼠心肌细胞凋亡的影响。方法:将74只雄性SD大鼠分为:正常对照组(A组)、心力衰竭组(B组)、睾丸切除加心力衰竭组(C组)、睾丸切除加心力衰竭加睾酮替代治疗组(D组)。通过超声心动图观察大鼠左室收缩功能的变化,应用放射免疫法检测大鼠血浆神经内分泌激素(睾酮)和肿瘤坏死因子-α水平,用凋亡原位检测方法(TUNEL法)检测心肌组织凋亡细胞,计算凋亡指数。结果:与B、C组比较,D组肿瘤坏死因子-α水平明显降低,心肌细胞凋亡指数减少,心功能也明显改善。结论:雄激素能抑制扩张型心肌病雄性大鼠心肌细胞的凋亡,从而保护了心功能,其作用的一个重要机制即是雄激素能拮抗肿瘤坏死因子-α的产生。     

Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure

OBJECTIVES: This individually randomized, open-label, parallel-group pilot study was designed to test the hypothesis that the ability of loop diuretics to interfere with cardiac fibrosis in chronic heart failure (CHF) may be different between compounds. BACKGROUND: The apparent mortality and cardiac benefits seen in studies comparing torasemide with furosemide in CHF suggest that torasemide may have beneficial effects beyond diuresis (e.g., on the process of cardiac fibrosis). METHODS: Patients with New York Heart Association functional class II to IV CHF received diuretic therapy with either 10 to 20 mg/day oral torasemide (n = 19) or 20 to 40 mg/day oral furosemide (n = 17), in addition to their existing standard CHF therapy for eight months. At baseline and after eight months, right septal endomyocardial biopsies were obtained to quantify collagen volume fraction (CVF) with an automated image analysis system. Serum carboxy-terminal peptide of procollagen type I (PIP) and serum carboxy-terminal telopeptide of collagen type I (CITP), indexes of collagen type I synthesis and degradation, respectively, were measured by specific radioimmunoassays. RESULTS: In torasemide-treated patients, CVF decreased from 7.96 +/- 0.54% to 4.48 +/- 0.26% (p < 0.01), and PIP decreased from 143 +/- 7 to 111 +/- 3 microg/l (p < 0.01). Neither CVF nor PIP changed significantly in furosemide-treated patients. In all patients, CVF was directly correlated with PIP (r = 0.88, p < 0.001) before and after treatment. No changes in CITP were observed with treatment in either group. CONCLUSIONS: These findings suggest that loop diuretics possess different abilities to reverse myocardial fibrosis and reduce collagen type I synthesis in patients with CHF.