慢性肾脏病并发左室肥厚现况及其危险因素

目的：探索中老年慢性肾脏病并发左室肥厚（LVH）的现况及其危险因素。方法：对我院肾内科住院的40-75岁CKD2-5期患者210例的病历资料进行回顾性分析。结果：（1）心脏舒张功能减退发生率高于收缩功能减退（79.1%VS 20.3%P=0.000）;左房扩大检出率高于左室扩大检出率（46.5%VS 19.8%P=0.000）;室间隔增厚检出率（IVSH）也高于左室后壁增厚检出率（LVPWH）（43.0%VS 21.1%P=0.000）;LVH的发生率高于IVSH检出率（47.9%VS 35%P=0.001）,其中女性LVH高于男性（73.2%VS31.0%P=0.000）,然而若采用另外一种诊断标准,两者并无统计学差异（50%VS 34.5%P=0.068）。（2）IVSH组收缩压、脉压、血肌酐均高于无IVSH组。IVSH组除上述因素外血磷尚高于无IVSH组,但在CKD5期的亚组分析中仅收缩压与对照组相比有统计学差异。LVH组收缩压、脉压均高于无LVH组,而血红蛋白、体质指数则低于对照组。进一步Logistic回归分析提示仅性别、体质指数有统计学意义。结论：（1）40-75岁的心血管疾病高危的CKD患者中,采用超声心动图诊断LVH,根据公式计算的LVMI诊断阳性率最高,但诊断切点仍需进一步研究。（2）收缩压升高、脉压增大、贫血、低体质指数、女性均可能是LVH的危险因素,控制血压、纠正贫血和营养不良可能是防治LVH的重要靶点。     

社区老年人慢性肾脏病患病率调查及其危险因素分析

目的:调查北京市通州区永顺社区老年人的慢性肾脏病(CKD)患病率,并分析其危险因素。方法:采用横断面调查方法,对该社区长期居住的65岁及以上的通州区户籍老年人进行问卷调查、肾脏损伤指标及其他实验室指标的检测,收集资料并分析CKD患病的危险因素。结果:本次调查共获得948例该社区常住老年人的完整资料,参与研究的老年人平均年龄为70.86±4.89岁;镜下血尿患病率为9.39%,白蛋白尿患病率为22.15%,5.70%的老年人出现肾功能下降,该人群中CKD患病率为36.81%(349/948)。单因素分析结果显示,两组吸烟史、饮酒史、血肌酐、体质量指数(BMI)、尿微量白蛋白肌酐比(ACR)、糖尿病、甘油三酯、总胆固醇及血尿酸水平对比无显著性差异(P0.05),而CKD组较非CKD组年龄更大、合并高血压的比例更高、女性占比更高(P0.05),多因素logistic回归分析显示年龄、女性与高血压是通州区永顺社区老年人CKD患病的危险因素(OR=1.432、1.163、1.335,P0.05)。结论:北京市通州区永顺社区老年人CKD患病率较高,其危险因素为年龄、女性与高血压。     

慢性肾脏病伴发高尿酸血症预后的回顾性研究

摘要 目的：本研究对慢性肾脏病伴发高尿酸血症的情况进行现状分析及随访,观察我院住院患者中符合该条件的人群,并对该人群是否较早进入以透析为主要方式的肾脏替代治疗阶段或是以死亡为主要表现的终点事件进行评估,以期降低肾脏病致死致残风险。方法：收集2013.1-2018.1在哈尔滨医科大学第一临床医院肾内科住院确诊为慢性肾脏病CKD1-5期患者的临床资料,进行回顾性分析。用SAS9.4软件统计数据,所得的数据以均值±标准差或者例数（百分比）的方式进行描述;方差齐时t检验应用于定量资料组间比较;方差不齐时应用Satterthwaite t''检验;完全随机设计的方差分析体现在多组间比较的应用。卡方检验是组间比较定性资料的一种选择。Pearson分析用来挖掘尿酸与本实验中其他指标的相关可能。采用单、多因素logistic回归分析汇总探讨慢性肾脏病的可能危险因素。结果：1）高尿酸血症组患者以24.93%的比例进入透析阶段,比非高尿酸组高了12.04%。死亡结果对两组之间的差异不构成影响。2）尿酸和胆固醇及血糖具有正相关关系,相关系数分别为0.12637 和0.11639。与eGFR具有负相关性,相关系数为-0.326。3) 单因素logistic回归分析CKD的危险因素结果表明年龄、尿酸、胱抑素C、尿素氮、血肌酐、尿蛋白、尿潜血、收缩压是CKD的危险因素。以CKD分期为应变量,单因素logistic 回归分析中有意义的变量为自变量,包括尿酸、尿蛋白、尿潜血、年龄、BUN、CysC、收缩压、血肌酐、吸烟、饮酒、BMI、甘油三酯、胆固醇、血红蛋白（Hemoglobin, Hb）进行多因素回归分析,变量筛选法采用向后法,结果显示,尿蛋白、尿素氮、尿酸是CKD独立危险因素。结论：1）与慢性肾脏病非高尿酸血症组相比,伴有高尿酸血症的慢性肾脏病患者进入透析阶段的比例更大。2）本研究可以得出尿蛋白、血尿素氮、尿酸是CKD的独立危险因素。     

AGT基因SNPs与哈萨克族高血压左室肥厚关系的研究

目的探讨血管紧张素原基因（angiotensinogen gene,AGT）-6A／G,-20A／C,M235T和T174M 4个单核苷酸多态性（single nucleotide polymorphisms,SNPs）与新疆哈萨克族高血压患者左室肥厚的关系。方法采用低渗溶血法破裂血细胞、蛋白酶K消化、饱和酚／氯仿抽提法提取白细胞基因组DNA。采用聚合酶链反应-限制性片断长度多态性（polymerase chain reaction—restriction fragment length polymorphism,PCR-RFLP）技术进行个体基因型分型。结果①在不考虑年龄、高血压病史时间、性别及收缩压、舒张压对左室肥厚的影响的前提下,未发现-6A／G、-20A／C与哈萨克族高血压左室肥厚的相关关系。②在以性别作为亚变量的分析结果中,我们发现-6A／G和-20A／C分别与哈萨克族女性和男性高血压左室肥厚相关。③不同SNPs间的配对连锁不平衡分析结果显示,除M235T与T174M之间外,其他各位点间存在有统计学意义的连锁不平衡关系。④单体型分析结果发现,研究人群AGT基因-6A／G、-20A／C、M235T和T174M4个SNPs构成了11种主要的单体型,其中H2（A—G—M—T）、H5（C—A—M—M）、H6（C—A-T—T）、H9（C-A—T—M）的频率在左室肥厚、非左室肥厚两组的分布存在差异,且具有统计学意义（P〈0．05）。结论AGT基因-6A／G、-20A／C、M235T和T174M变异可能与新疆哈萨克族高血压左室肥厚有关。     

慢性肾脏病患者心脏结构与功能变化的超声心动图研究

目的:研究慢性肾脏病(CKD)患者心脏结构及功能的变化.方法:选择我院肾内科175例慢性肾脏病未透析患者,按照2003年美国国家肾脏基金会-肾脏病转归质量(NKF-K/DOQI)指南的标准进行分期,观察所有患者心脏结构及功能在超声中的变化.结果:慢性肾脏病患者随着肾功能的恶化,各组之间比较,室间隔厚度(IVST)、左心室后壁厚度(LVPW)、左心室心肌重量指数(LVMI)、左心室舒张末期内径(LVDd)、左心房内径(LAD)具有升高的趋势(P＜0.05,P＜0.01);但E/A比值未出现伴随着肾功能恶化而逐渐减低的趋势(P＞0.05);射血分数(EF)、短轴缩短卒(FS)在各期之间无明显变化(P＞0.05);而TVI技术测定的Em、Em/Am具有显著减低的趋势(P＜0.05,P＜0.01);瓣膜返流以二尖瓣返流为主.结论:慢性肾脏病患者心脏结构与功能随肾功能减退而加重,超声心动图检查结合组织速度显像(TVI)技术能更好地检测心脏结构和功能变化,尤其是检测左心室舒张功能障碍.     

慢性支气管炎住院患者机械通气的危险因素分析

目的：分析慢性支气管炎住院患者进行辅助机械通气的危险因素。方法：采取回顾性统计分析方法,收集2009-2014 年5 年 中共1746 例慢性支气管炎住院患者的临床资料,应用SPSS 17 软件分组对年龄、性别、肺气肿、慢性肺源性心脏病、肺性脑病、肺 大泡、肺炎、支气管扩张、哮喘、冠心病、高血压病、糖尿病、低蛋白血症、贫血、肝功能异常、肾功能异常等因素进行卡方检验及危 险因素分析。结果：1746 慢性支气管炎患者中,进行辅助机械通气治疗者626 人（无创辅助通气613人、有创辅助通气187 人）,未 进行辅助机械通气治疗者1120人。辅助机械通气治疗者中有439 人单纯行无创辅助通气、13 人单纯行有创辅助通气、174 人为 两种通气方式序贯。统计分析显示：高龄（＞ 65岁）、慢性肺气肿、慢性肺源性心脏病、肺性脑病、糖尿病、低蛋白血症、肝功能异常、 肾功能异常是慢性支气管炎患者行无创辅助通气的危险因素（OR＞1,P<0.05) ;高龄（＞65 岁）、男性、慢性肺源性心脏病、肺性脑 病、肺炎、糖尿病、低蛋白血症、贫血、肝功能异常、肾功能异常是慢性支气管炎患者行有创辅助通气的危险因素（OR＞1,P<0.05)。 结论：高龄、性别以及一些肺内外合并疾病是慢性支气管炎住院患者行辅助通气的危险因素,提示在临床工作中对这一类患者加 强教育、积极控制合并症具有重要的意义。     

超声心动图对高血压心室肥厚患者左心功能的评价及意义

目的:本研究利用超声心动图检测高血压心室肥厚患者左心房结构,探讨当左心结构发生变化时心脏功能所受到的影响,为高血压及其并发症的临床诊断提供检测及诊断参考。方法:选取2011年5月-2013年1月在我院接受检查的高血压心室肥厚患者76例作为观察组,另选取同期经体检的健康人群60例为健康对照组,利用超声心动图观察左心功能和结构,比较两组研究对象的左心房内径(LAD)、心肌质量(LVMM)、舒张末容积(LVEDV)、收缩末容积(LVESV)、左心室射血分数(LVEF)及二尖瓣口舒张末期流速比值(E/A)。结果:两组间心室收缩功能无显著性差异(P0.05);高血压组LAD高于对照组,LVEF及E/A低于对照组,差异具有统计学意义(P0.05);高血压Ⅰ期、Ⅱ期、Ⅲ期患者间比较,左房内径随血压的升高逐渐递增,而左心室射血分数和二尖瓣口舒张期流速比值则逐渐递减,差异具有统计学意义(P0.05)。结论:超声心动图可以直观的显示高血压心室肥厚患者左心功能及血流动力学的变化,对临床诊断具有积极的意义。     

慢性肾脏病患者胰岛素抵抗的发生情况及其影响因素分析

目的:探究慢性肾脏病(chronic kidney disease,CKD),尤其是非肥胖CKD患者,胰岛素抵抗(insulin resistance,IR)的发生情况,并分析其影响因素。方法:按照纳排标准,选择2016年1月至2017年11月在解放军总医院肾病科就诊的CKD患者共573例,其中非肥胖CKD患者510例,检测患者的身高、体重、空腹胰岛素、血肌酐、血尿素氮等临床指标,计算患者身高体重指数(body mass index,BMI),以BMI≥28 kg/m~2定义为肥胖,按照e GFR水平将CKD分期,建立HOMA指数(HOMA-IR)稳态模型评价IR情况,对CKD患者及非肥胖CKD患者各期IR的发生率进行比较,应用单因素相关性分析和多元逐步回归分析进行HOMA-IR指数相关因素的研究。结果:随着CKD患者肾脏功能的逐渐恶化,IR的发生率逐渐升高。各期CKD患者及非肥胖CKD患者IR的发生率比较差异均具有统计学意义(P=0.019,P=0.000)。在单因素相关性分析结果显示CKD患者的HOMA-IR指数与BMI、血尿素氮、甘油三酯、甲状旁腺激素、CKD分期呈正相关,与总蛋白、白蛋白、高密度脂蛋白、e GFR呈负相关。非肥胖CKD患者的HOMA-IR指数与年龄、尿素氮、甘油三酯、甲状旁腺激素、CKD分期呈正相关,与总蛋白、白蛋白、高密度脂蛋白、e GFR呈负相关。多元回归分析显示CKD患者的BMI、血尿素氮、甘油三酯、CKD分期进入最终回归方程,HOMA-IR与BMI、血尿素氮、甘油三酯、CKD分期呈正相关(P0.05)。非肥胖CKD患者的尿素氮、甲状旁腺激素、CKD分期进入最终回归方程,HOMA-IR与尿素氮、甲状旁腺激素、CKD分期呈正相关(P0.05)。结论:IR的发生率随CKD的进展逐渐升高,肥胖、血尿素氮升高、甘油三酯升高、肾功能降低是CKD患者发生IR的相关危险因素,血尿素氮升高、甲状旁腺激素升高、肾功能降低是非肥胖CKD患者IR发生的相关危险因素。     

慢性肾脏病患者心脏结构与功能变化的超声心动图研究(英文)

目的:研究慢性肾脏病(CKD)患者心脏结构及功能的变化。方法:选择我院肾内科175例慢性肾脏病未透析患者,按照2003年美国国家肾脏基金会-肾脏病转归质量(NKF-K/DOQI)指南的标准进行分期,观察所有患者心脏结构及功能在超声中的变化。结果:慢性肾脏病患者随着肾功能的恶化,各组之间比较,室间隔厚度(IVST)、左心室后壁厚度(LVPW)、左心室心肌重量指数(LVMI)、左心室舒张末期内径(LVDd)、左心房内径(LAD)具有升高的趋势(P<0.05,P<0.01);但E/A比值未出现伴随着肾功能恶化而逐渐减低的趋势(P>0.05);射血分数(EF)、短轴缩短率(FS)在各期之间无明显变化(P>0.05);而TVI技术测定的Em、Em/Am具有显著减低的趋势(P<0.05,P<0.01);瓣膜返流以二尖瓣返流为主。结论:慢性肾脏病患者心脏结构与功能随肾功能减退而加重,超声心动图检查结合组织速度显像(TVI)技术能更好地检测心脏结构和功能变化,尤其是检测左心室舒张功能障碍。     

慢性心力衰竭院内感染病原菌监测及危险因素分析

目的:探究慢性心力衰竭(CHF)患者医院感染的现状、病原菌分布及耐药情况,分析CHF患者发生医院内感染的危险因素。方法:选择2012年9月~2015年9月中心医院及开发区分院收治的390例CHF患者为研究对象,根据CHF患者是否发生医院内感染将其分为观察组(感染患者41例)和对照组(未感染患者349例);收集患者基线资料,对观察组患者进行病原菌培养及药敏实验,分析CHF患者发生医院内感染的危险因素。结果:CHF患者中医院感染的发生率为10.51%(41/390),感染部位以呼吸道19例(46.34%)和泌尿道12(29.27%)为主;前三位的病原菌为铜绿假单胞菌14株(29.79%)、大肠埃希菌11株(23.40%)和肺炎克雷伯菌8株(17.02%);铜绿假单胞菌、大肠埃希菌和肺炎克雷伯菌对头孢哌酮、美罗培南及亚胺培南均具有药物敏感性;年龄≥60岁(OR=2.26,P0.05)、住院时间≥2两个月(OR=5.12,P0.05)、有侵袭性操作(OR=7.45,P0.05)、病程长(OR=4.36,P0.05)是CHF患者发生医院内感染的危险因素。结论:CHF患者医院感染的发生率较高,年龄≥60岁、住院时间≥2个月、侵袭性操作及病程5年是CHF患者发生医院内感染的危险因素;应当针对患者医院感染特点及药敏实验结果,采取针对性的预防措施和对策,有效控制及降低医院感染的发生。     

Phospholipase D: A new mediator during high phosphate-induced vascular calcification associated with chronic kidney disease

Vascular calcification (VC) is the pathological accumulation of calcium phosphate crystals in one of the layers of blood vessels, leading to loss of elasticity and causing severe calcification in vessels. Medial calcification is mostly seen in patients with chronic kidney disease (CKD) and diabetes. Identification of key enzymes and their actions during calcification will contribute to understand the onset of pathological calcification. Phospholipase D (PLD1, PLD2) is active at the earlier steps of mineralization in osteoblasts and chondrocytes. In this study, we aimed to determine their effects during high-phosphate treatment in mouse vascular smooth muscle cell line MOVAS, in the ex vivo model of the rat aorta, and in the in vivo model of adenine-induced CKD. We observed an early increase in PLD1 gene and protein expression along with the increase in the PLD activity in vascular muscle cell line, during calcification induced by ascorbic acid and β-glycerophosphate. Inhibition of PLD1 by the selective inhibitor VU0155069, or the pan-PLD inhibitor, halopemide, prevented calcification. The mechanism of PLD activation is likely to be protein kinase C (PKC)-independent since bisindolylmaleimide X hydrochloride, a pan-PKC inhibitor, did not affect the PLD activity. In agreement, we found an increase in Pld1 gene expression and PLD activity in aortic explant cultures treated with high phosphate, whereas PLD inhibition by halopemide decreased calcification. Finally, an increase in both Pld1 and Pld2 expression occurred simultaneously with the appearance of VC in a rat model of CKD. Thus, PLD, especially PLD1, promotes VC in the context of CKD and could be an important target for preventing onset or progression of VC.     

Detection of advanced oxidation protein products in patients with chronic kidney disease by a novel monoclonal antibody

Abstract

Advanced oxidation protein products (AOPP) as a biomarker of oxidative stress has been demonstrated in chronic kidney disease (CKD) patients; however, current methods to detect the accumulation of AOPP in serum and in tissues are limited and unreliable. This study generated a monoclonal antibody (mAb) designated 3F2, that reacts specifically with hypochlorous acid (HOCl)-modified proteins, but not with the native forms or with other types of oxidative modifications. Notably, mAb 3F2 recognizes the AOPP deposited in renal tissues of AOPP-treated rats and of patients with different kinds of CKD. Moreover, this mAb can almost completely inhibit the production of reactive oxygen species in RAW264.7 cells induced by AOPP (p < 0.001). In conclusion, mAb 3F2 can be used to detect AOPP specifically in serum and in tissues, and this antibody can potentially provide an important tool and new insight into research on diseases related to oxidative stress.     

Calcium dysregulation increases right ventricular outflow tract arrhythmogenesis in rabbit model of chronic kidney disease

Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)-induced sustained VT, and long duration of isoproterenol and tachypacing-induced sustained and non-sustained VT. Tachypacing-induced sustained and non-sustained VT in isoproterenol-treated CKD RVOT tissues were attenuated by KB-R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase-positive neural density. The CKD RVOT myocytes exhibited large levels of I_to, I_Kr, NCX and L-type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.     

Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility

Organ–organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation. Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor-α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.     

Low- and moderate- levels of arsenic exposure in young adulthood and incidence of chronic kidney disease: Findings from the CARDIA Trace Element Study

BackgroundIt is unclear whether arsenic exerts adverse health effects on the kidney at low- and moderate- levels of exposure. We prospectively examined toenail arsenic concentrations measured during young adulthood in relation to incidence of chronic kidney disease (CKD) in midlife.MethodsA total of 3768 participants (53 % female and 48 % blacks) in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Arsenic concentration in toenail clippings was assessed by using inductively coupled plasma mass spectrometry at CARDIA exam year 2. Incident CKD was identified if having estimated glomerular filtration rate <60 mL/min per 1.73 m² or albuminuria >30 mg/g. The association between toenail arsenic levels and CKD incidence over a mean of 24 years of follow-up was examined using multivariable-adjusted Cox proportional hazards models.ResultsAfter controlling for potential confounders, including demographics, socioeconomics, lifestyle factors, clinical measurements of blood pressure, lipids, and glucose, and medical history, arsenic exposure measured in toenails was not associated with CKD incidence (quintile 5 versus quintile 1: hazard ratio = 1.04, 95 % confidence interval = 0.78–1.40, P for trend = 0.38).ConclusionThis longitudinal study does not support the hypothesis that low- and moderate- levels of arsenic exposure are associated with elevated incidence of CKD in the US general population. Further studies are need to investigate species of arsenic biomarkers in relation to nephrotoxicity.     

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress,autophagy and apoptosis

The interplay between H₂S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H ₂S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L -NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester ( L -NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H ₂S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD.     

Increased gene expression of plasminogen activators and inhibitors in left ventricular hypertrophy

In the early stages of left ventricular hypertrophy (LVH) acute adaptive changes occur in the coronary vasculature as it remodels. Plasminogen activators (PAs) and inhibitors (PAIs) have the potential effects of proteolytic degradation that is relevant to tissue remodeling and angiogenesis. Our study focused on the possible roles of PAI-1, PAI-2, uPA and tPA in myocyte hypertrophy and angiogenesis in the early and late stages of pressure overload induced left ventricular hypertrophy (LVH). We divided seventeen adult swine, weighing 24.2 ± 6.5 kg, into four groups: control, sham-operated, early LVH and late heart failure LVH group. At surgery we placed a fixed constrictor on the ascending aorta immediately above the aortic valve. This increased LV systolic pressure from 133 ± 15 to 193 ± 24 mm Hg after the surgery. We subdivided the early group into groups of 3 animals each that we euthanized at 8, 24 and 72 h after operation and obtained heart samples for analysis. In the late heart failure group individual animals were euthanized at 55, 59, 62 and 72 days after the detection of congestive heart failure. We also obtained tissue samples from the control and sham-operated swine. Sections for histologic analysis were fixed in 10% buffered formalin. We isolated RNA, size fractionated it using 1% formaldehyde-agarose gel electrophoresis and then did Northern blots. The mRNAs from both PAI-1 and PAI-2 showed a remarkable increase at 8 and 24 h after acute aortic constriction and returned to control by 72 h. Regional differences showed that most of the increases were in the endocardium. Three animals in the late heart failure LVH group were determined to be in congestive heart failure at about 2 months after the onset of aortic constriction. In these animals PAI-1 and PAI-2 were increased in both the left and right ventricles but remained low in an animal of the same elevation in aortic pressure seen by the LV who did not have congestive failure. These data suggest that PA and PAI gene expressions change before morphologic changes occur in the early stages of developing LVH. Also at the time of onset of congestive heart failure this increased expression reappears. PAs and PA inhibitors mRNA levels vary in the different regions of the heart reflecting changing wall stresses. Thus, the PAs and PA inhibitors may play an important role in angiogenesis that occurs during the early stages of LVH. The increased expression in the late stage of LVH may reflect further changes in wall stresses since these animals also showed overt clinical signs of heart failure.     

Relationship of the maximum QRS vector with the left ventricular myocardial mass during the development of hypertrophy: Computer simulation and empirical data

A model of electrical activity of the heart has been used to demonstrate that, all other conditions remaining the same, the spatial vector of the heart changes, as a first approximation, proportionally to the increase in the surface area of the heart ventricles (rather than the myocardial mass) during proportional homothetic changes in the sizes of the heart and His-Purkinje system. In contrast, the electrocardiosignal (ECS) amplitude is determined, at any given moment, by the area of depolarized regions of the epicardium and endocardium, which agrees with the model of a double electrical layer on the surface of an electrically active myocardium.