当归挥发油含药血清对肥大心肌细胞钙离子浓度的影响

目的:研究当归挥发油含药血清对肥大心肌细胞钙离子浓度的影响。方法:超临界萃取当归挥发油,制备含药血清。原代培养大鼠心肌细胞,血管紧张素(Ang)Ⅱ诱导制备心肌细胞肥大模型,5%当归挥发油含药血清进行干预。以图像分析软件测量心肌细胞表面积,考马斯亮蓝法测定心肌细胞蛋白含量,Fluo-3测定肥大心肌细胞内Ca2+荧光强度变化。结果:AngⅡ组(10-7 mmol/L)心肌细胞表面积、蛋白含量均明显增加,与空白组相比(P0.05),心肌细胞肥大模型成功建立。5%当归挥发油含药血清处理组细胞内钙离子浓度明显下降,与AngⅡ组相比(P0.05),当归挥发油可减少AngⅡ(10-7 mmol/L)诱导的肥大心肌细胞内Ca2+的浓度。结论:当归挥发油含药血清可能对AngⅡ诱导的肥大心肌细胞具有钙通道阻滞的作用。     

黄芪抑制去甲肾上腺素诱导大鼠心肌细胞内游离钙含量升高的作用

目的 :研究黄芪对去甲肾上腺素 (NE)诱导大鼠心肌细胞内游离钙 [Ca2 + ]i 含量升高的作用。方法 :应用AR CM MIC阳离子检测系统 ,采用Ca2 + 指示剂Fura 2 /AM检测培养新生大鼠单个心肌细胞内游离钙的浓度 ,并观察Am对NE诱导大鼠心肌细胞内 [Ca2 + ]i 升高的影响。结果 :当细胞外Ca2 + 浓度为 1 .3mmol/L时 ,大鼠心肌细胞 [Ca2 + ]i 为 ( 97.1 1 +8.2 1 )nmol/L ,给予 1 0 -5mol/L的NE ,可使大鼠心肌细胞 [Ca2 + ]i 增至 ( 2 91 .73± 1 5 .0 3 )nmol/L,而经黄芪处理的大鼠心肌细胞的 [Ca2 + ]i则由 ( 95 .98±8.1 4)nmol/L增至 ( 1 1 4.2 8± 9.2 9)nmol/L。结论 :NE能诱导大鼠心肌细胞内游离钙含量明显升高 ,黄芪对心肌细胞静息 [Ca2 + ]i无明显影响 ,但能抑制NE诱导大鼠心肌细胞 [Ca2 + ]i 升高     

地高辛增加心肌收缩力治疗心衰的细胞学机制(96)

<正>有强心作用的地高辛,其药理作用的主要机制是抑制心肌细胞膜上的钾钠ATP酶,进而抑制心肌细胞膜上钠泵的运转,结果使钠泵将心肌细胞外K+打进细胞内的作用,以及将细胞内的Na+打到细胞外的作用减弱,使心肌细胞内的Na+浓度轻度升高。心肌细胞内Na+浓度的这种轻度升高将增加心肌细胞膜上钠钙交换体的活性,使较多的Na+经该交换体打到细胞外,同时交换回更多的Ca2+进入心肌细胞内。     

慢性低氧后钙转运的变化(英文)

目的 :本文研究大鼠慢性低氧后心肌钙转运的变化。方法 :将大鼠放置于 10 %氧环境下 4周 ,分离正常及慢性缺氧大鼠的右心室肌细胞 ,用光谱荧光法测定电刺激和咖啡因引起的细胞内 [Ca2 + ]i瞬变 ,并测定肌浆网膜上的Ca2 + ATP酶 （SERCA）和ryanodine受体 （RyR）蛋白的水平。结果 :低氧后电刺激和咖啡因引起的细胞内 [Ca2 + ]i瞬变的幅度降低且时程延长 ,RyR水平无明显改变但SERCA已显著减少。结论 :Ca2 + ATP酶活性和蛋白水平的降低是低氧钙转运异常的主要原因。     

洛沙坦对甲状腺素诱导的大鼠心肌肥厚的影响

目的:研究血管紧张素Ⅱ1型受体拮抗剂洛沙坦对甲状腺素诱导的心肌肥厚的影响.方法:SD大鼠ip左甲状腺素0.5 mg@kg-1@d-1×10 d,造成心肌肥厚模型.同时洛沙坦ig 40 mg@kg-1@d-1×10 d.观察心重指数,心肌胶原浓度,心肌细胞直径,心肌胶原容积分数;心肌肌球蛋白ATP酶,细胞膜和线粒体Na+,K+-ATP酶,Ca2+-ATP酶.结果:洛沙坦能阻止心肌肥厚的发生,降低心重指数,减少胶原合成,提高肌球蛋白ATP酶活力及细胞膜和线粒体Na+,K+-ATP酶,Ca2+-ATP酶活力.结论:洛沙坦可防止甲状腺素诱导的心肌重塑.     

羟自由基诱导心肌细胞损伤时ATP酶等变化

目的　探讨外源性羟自由基诱导乳鼠心肌细胞损伤的作用机理。方法　采用 Fe SO4 / H2 O2 产生系统 ,羟自由基诱导心肌细胞损伤 ,观察乳鼠心肌细胞内 Na+、K+ - ATP酶 ,Ca2 +、Mg2 + - ATP酶和丙二醛 (MDA)含量及其上清液中乳酸脱氢酶 (L DH)与一氧化氮 (NO)含量变化。结果　心肌细胞中 Na+、K+ - ATP酶 ,Ca2 +、Mg2 + - ATP酶减少 ,MDA含量增加 ,与对照组相比较 ,具有显著性差异 (P<0 .0 1,P<0 .0 5 ,P<0 .0 1) ;上清液中 L DH和 NO漏出增加 ,与对照组相比较 ,均具有显著性差异 (P<0 .0 1)。结论　羟自由基诱导心肌细胞中 Na+ 、K+ - ATP酶 ,Ca2 + 、Mg2 + - ATP酶减少 ,MDA及其上清液中 L DH和 NO漏出增加。从而揭示外源性羟自由基可能通过增加膜脂质过氧化 ,引起 ATP酶失活及膜结构破坏等 ,是导致心肌细胞死亡的机理之一     

钙稳态失衡在致结肠平滑肌收缩性改变中的作用

目的　探讨应激大鼠结肠平滑肌收缩时细胞内外钙离子 (Ca2 +)利用异常、细胞内钙稳态失衡在导致其收缩性改变中的作用。方法　建立寒冷 束缚应激大鼠排便异常的动物模型 ;测定离体结肠环形平滑肌收缩张力 ;差速离心制备结肠平滑肌肌浆网 ,测定肌浆网Ca2 + ATP酶活性。结果　应激大鼠结肠平滑肌收缩活性明显增强 ,并受Ca2 +通道阻滞剂显著抑制。应激大鼠结肠平滑肌肌浆网Ca2 + ATP酶活性降低 5 6 % (P <0 .0 5 )。结论　应激大鼠结肠环形平滑肌收缩活性显著增强 ,可能和肌细胞收缩时细胞外Ca2 +内流增加 ,肌浆网贮存Ca2 +释放减少、Ca2 + ATP酶活性降低等因素导致细胞内钙稳态失衡有关     

参麦注射液对心肌缺血再灌注损伤大鼠钙调神经磷酸酶活性的影响

目的探讨参麦注射液(SMI)对大鼠心肌缺血再灌注损伤(MIRI)中钙调神经磷酸酶(CaN)活性变化的影响。方法 30只大鼠随机分为假手术组、模型组和SMI组各10只,检测各组心肌CaN变化,并测定其心肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)、腺苷三磷酸(ATP)、CaN活性。结果与假手术组比较,模型组CaN活性、心肌细胞凋亡率、MDA含量明显升高(P<0.01),SOD含量、Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性明显下降(P<0.01);与模型组比较,SMI组CaN活性、心肌细胞凋亡率、MDA含量明显下降(P<0.05),SOD含量、Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性明显升高(P<0.05)。结论 SMI能够抑制大鼠心肌细胞CaN活性,对缺血再灌注心肌有一定保护作用。     

酸性复灌液对再灌注未成熟心肌细胞线粒体功能的影响

目的:观察酸性复灌液对未成熟心肌细胞线粒体功能的作用。方法:采用兔Langendorff离体心脏灌注模型,分为缺血/再灌组(I/R组,8只)和酸性灌注组(E组,8只)。I/R组灌流20min后缺血60min,用pH7.4HEPES-KH液恢复灌注100min;E组pH 7.4HEPES-KH液灌流20min后缺血60min,用pH 6.8、pH 7.1和pH 7.4HEPES-KH液依次灌注5min、5min和90min。测定心肌组织ATP含量、心肌细胞内和心肌线粒体Ca2+含量、心肌线粒体Ca2+-ATPase活性、心肌线粒体合成ATP能力[ATP]m、心肌线粒体超微结构。结果:与I/R组相比,E组ATP含量、心肌线粒体Ca2+-ATPase活性和[ATP]m均优于I/R组(均P0.01),心肌细胞内和心肌线粒体Ca2+含量均低于I/R组(均P0.01),E组线粒体结构损伤较I/R组明显减轻。结论:梯度酸性复灌液对离体未成熟心肌细胞线粒体功能具有明显保护作用。     

PI3K阻断剂LY294002对TNF-α诱导心肌肥大的Ca~(2+)-CaMKⅡ和CaN通路的影响

目的研究PI3K是否通过Ca2+-Ca MKⅡ和Ca N信号途径参与肿瘤坏死因子-α诱导的心肌肥大。方法应用激光共聚焦显微镜检测单个心肌细胞内Ca2+浓度变化。Lowry法测心肌细胞蛋白含量。计算机图象分析测心肌细胞体积。应用Western blot法测定心肌细胞Ca MKⅡδB和Ca N蛋白表达。结果 1PI3K阻断剂LY294002(50μmol/L)明显抑制TNF-α(100μg/L)诱导的心肌细胞内钙离子浓度增高(P0.01),对正常心肌细胞内Ca2+浓度无明显影响。其抑制程度与LY294002+2-APB(30μmol/L)组相近(P0.05),小于LY294002+ryanodine(50μmol/L)组(P0.05)。2LY294002明显抑制TNF-α诱导的心肌细胞蛋白含量的增加及细胞体积的增大;其程度与LY294002+2-APB无统计学差异,但大于单用2-APB组,小于LY294002+ryanodine组(P0.05)。PI3K阻断剂LY294002明显抑制TNF-α诱导的心肌细胞Ca MKⅡδB和Ca N表达增加(P0.01),其抑制程度与LY294002+2-APB组相近(P0.05)。结论 PI3K通过作用IP3R使心肌细胞内Ca2+浓度增加,进而调节心肌细胞内Ca MKⅡδB和Ca N的表达,从而参与TNF-α诱导的心肌肥大。     

Appraisal of polyethyleneimine used as a tracer for anionic sites in human cardiac tissues with a brief reference to anionic molecular organization in altered basement membranes

Electron microscopic cytochemical studies on human ventricular muscles obtained during open heart surgery were carried out in ten patients with tetralogy of Fallot. Polyethyleneimine was used as a tracer for demonstration of anionic sites in the membrane surfaces of myocardial cells and capillaries. In the myocardial cells PEI particles were consistently observed to be orderly arranged in the external lamina of normal basement membranes at regular spacings of 40 to 80 nm. Few PEI particles were irregularly dispersed in the surface coat of basement membranes and the interspaces of intercalated discs. PEI particles were also seen to be regularly distributed in normal capillary basement membranes, mainly restricted in outer lamina densa at intervals of 40 to 80 nm. It was of particular interest that PEI particles were often seen to be irregularly and loosely arranged in abnormally thickened basement membranes of myocardial cells and capillaries. In addition, focal loss of PEI deposition in altered basement membranes was a frequent finding. Based on electron microscopic cytochemical findings the following conclusions are made: The anionic sites characterized by PEI which is considered to be superior to most polycationic colloids show a regular lattice-like arrangement in the basement membranes of human myocardial cells and capillaries; Anionic groups which are not distributed uniformly on human myocardial cell surfaces show different distribution patterns in the external lamina and surface coat of basement membranes; and Perturbations of regular anionic arrays are demonstrable in altered basement membranes of diseased human myocardium.     

Altered calcium regulation in the cardiac plasma membrane in experimental renal hypertension

The factors regulating calcium homeostasis in the cardiac plasma membrane of renal hypertension in the rat (two kidney-one clip, Goldblatt model) have been studied. Comparison of the cardiac sarcolemma from control (C) and hypertensive (H) rats indicates similar protein yield and purity. Study of longer term hypertension (4 to 12 weeks) shows a decrease in the number of calcium channel receptor binding sites (Bmax C: 549 +/- 122 fmol/mg; H: 334 +/- 74 fmol/mg) as well as a depressed calcium pumping ATPase activity (C: 7.6 +/- 2.5 nmol/mg/min; H: 3.8 +/- 1.5 nmol/mg/min). Furthermore, there is a decreased rate of Na+-Ca2+ exchange (C: 5.4 +/- 1.9 nmol/mg/5 s; H: 2.3 +/- 0.9 nmol/mg/5 s). Study of short-term hypertension (1 to 4 weeks) indicates that the earliest change occurs at 1 week with decreased calcium pumping ATPase due to a change of the Vmax of Ca2+ transport (C: 9.7 +/- 1.6 nmol/mg/min; H: 5.4 +/- 1.4 nmol/mg/min). This is then followed by the decreased calcium channel receptor binding. However, the rate and the extent of depression in Ca2+-ATPase activity are much greater than that of Ca2+ channel receptor binding. Since alteration of Ca2+-ATPase is accompanied by an increase in intracellular Ca2+ concentration and there is a temporal association with the onset of myocardial lesions in the hypertensive rats, it is suggested that elevated intracellular calcium concentration as a result of altered Ca2+-ATPase activity may play a significant role in the development of hypertensive cardiomyopathy.     

Calcium at the sarcolemma

Experiments in mammalian ventricle in which calcium (Ca) is removed from and replaced to arterial perfusate indicate that a component of Ca important in contractile control is bound to rapidly exchangeable cellular sites. These sites appear to be in rapid equilibrium with extracellular Ca and are replenished, beat-to-beat, from the extracellular source. The binding sites appear to be anionic phospholipids of the sarcolemma. They are visualized to represent a store of sarcolemmal Ca which, upon membrane excitation, supplies the systems responsible for transsarcolemmal movement--the Ca channel and the Na-Ca exchanger. The amount of Ca bound to sarcolemma is an important factor in control of the amount of Ca which enters the cell via the channel or exchanger. Conversely, there is evidence that suggests that the activity of (at least) the exchanger determines, in part, the quantity of Ca bound. Increased activity of the Na-Ca exchanger is associated with increased Ca-binding to sarcolemmal sites.     

Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy

Summary Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- and sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2–62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2–0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites × mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.Abbreviations HS Heparan sulphate - GBM glomerular basement membrane - HSPG heparan sulphate proteoglycan - STZ streptozotocin - LRE lamina rara externa - LD lamina densa - LD + LRI lamina densa + lamina rara interna - ANOVA analysis of variance     

Heart sarcolemmal ATPase and calcium binding activities in rats fed a high cholesterol diet

ATPase and calcium binding activities were studied in sarcolemmal membranes from hearts of male rats fed either a control or 2% cholesterol diet for different time periods. Studies with isolated membrane revealed a significant increase in Na+-K+ ATPase activity, sialic acid content and ATP-independent calcium binding capacity in the presence of 1.25 mM CaCl2 in the 6 week cholesterol fed group. By 12 weeks, Na+-K+ ATPase, Mg2+-ATPase and Ca2+-ATPase activities as well as ATP-independent calcium binding in the presence of 0.05 mM CaCl2 were increased in membranes from cholesterol fed rats. A significant increase (P less than 0.05) in the sarcolemmal cholesterol/phospholipid molar ratio, which is an indicator of a decrease in membrane fluidity, was also noted in the 12 week cholesterol fed group. Concanavalin A, which is believed to decrease membrane fluidity, stimulated both Mg2+ and Ca2+-dependent ATPase activities and increased ATP-independent calcium binding in control sarcolemmal preparations and these changes resembled those observed in the sarcolemma from cholesterol fed rats. Since concanavalin A did not alter the activity of Na+-K+ ATPase, it appears that some of the observed differences in sarcolemmal activities upon cholesterol feeding did not correlate well with changes in membrane order. At 24 weeks, there was a generalized depression in the sarcolemmal ATPase activities of the cholesterol group; both Mg2+ ATPase and Ca2+ ATPase were significantly less than in control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modification of anionic sites in myocardial capillary basal laminae of diabetic rats

Capillary basal laminar thickening is a distinctive feature of diabetic microangiopathy; however, the mechanism responsible for this abnormality remains to be clarified. Recent reports have described a reduction in the distribution of anionic sites in diabetic glomerular basement membranes, with the suggestion that this reduction may generate a compensatory synthesis of basal laminar constituents, causing laminar thickening. In order to provide additional information, the character and distribution of the basal laminar anionic profile were examined in the myocardium of diabetic rats. Diabetes mellitus was induced in 14 rats by injection with streptozotocin, ip; 6 rats served as controls. Myocardial tissue was subjected to Charonis' procedure for the demonstration of anionic sites with the cationic electron-dense dye, ruthenium red, following the sacrifice of the animals at intervals up to 11 months after the induction of the diabetes. The tissues were then processed routinely for electron microscopic examination. A total of 20 electron micrographs, at magnifications of 13,000x and 33,000x, were obtained from each rat for the quantitation of anionic sites. A length measuring 6 micron along each basal lamina was utilized for determining the number of anionic loci. Results of this study show that (1) the number and size of anionic sites in myocardial basal laminae is reduced in diabetic rats, (2) this decrease becomes more pronounced with prolongation of the diabetes, (3) it is detectable prior to the demonstration of basal laminar thickening by electron microscopy, and (4) enzyme digestion treatments indicated that heparan sulfate proteoglycan is the essential stainable component of the anionic sites. These findings provide evidence that the laminar anionic profile is altered in the diabetic myocardium and support the view that this abnormality constitutes a significant initial event in the pathogenesis of basal laminar thickening.     

Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit.

We studied hearts from sham-operated and uninfected catheterized rabbits as well as from rabbits at early and late stages of cardiomyopathy and failure after 3 and 6 days of infection with Streptococcus viridans. No ultrastructural abnormalities or biochemical changes in membrane and myofibrillar activities were seen in 3-day uninfected hearts. In 6-day uninfected hearts there were decreased sarcolemmal M2+ ATPase, Na+-K+ ATPase, adenylate cyclase and calcium binding, microsomal calcium binding and uptake, and myofibrillar Ca2+-stimulated ATPase as well as increased mitochondrial calcium uptake. Slight ultrastructural changes also were apparent in 6-day uninfected hearts. At both early and late stages of infective cardiomyopathy and failure there were varying degrees of depression in sarcolemmal Mg2+ ATPase, Na+-K+ ATPase, adenylate cyclase and calcium binding, microsomal calcium binding, calcium uptake and basal ATPase, and myofibrillar Ca2+-stimulated ATPase activities. However, sarcolemmal Ca2+ ATPase and myofibrillar Mg2+ ATPase activities were decreased only after 6 days of infection. Mitochondrial calcium binding and uptake were increased in early stages but decreased in late stages of disease. Furthermore in infected hearts there were defects in mitrochondrial respiration and phosphorylation. Generalized severe myocardial cell damage involving myofibrils, mitochondria, and the sarcotubular system was seen only in late stages of infection. The results demonstrate impairment of different membrane and contractile protein functions as well as ultrastructural abnormalities in bacterial cardiomyopathic hearts which were absent or of lesser magnitude in hearts with only hypertrophy. The findings reported here suggest to use that there is an association between heart failure and changes in function of cellular components during bacterial infective cardiomyopathy.     

Na,K-ATPase and Ca-ATPase activities of the myocardial sarcolemma in aging rats after aorta coarctation: role of invertors.

In this work we used aorta coarctation as a model of myocardial hypertrophy. We studied the role of intracellular regulators of plasma membrane status-invertors-in the mechanisms of changes of membrane enzyme activities in the emergency stage of myocardial hypertrophy. We used Wistar rats of various ages: adult (6-8 months) and old (26-28 months) rats. It was shown that 4-6 days after aorta coarctation, in adult rats the activities of both Na,K-ATPase and Ca-ATPase of the sarcolemma of cardiomyocytes increased, but in old rats only the Ca-ATPase activity. Experiments with cell hybrids (cytosol of experimental rats and isolated sarcolemma of cardiomyocytes of intact rats) revealed that cytosol of cardiomyocytes of adult animals after aorta coarctation activated Na, K-ATPase and Ca-ATPase. Cytosol of old intact animals after aorta coarctation did not activate Na,K-ATPase, but activated Ca-ATPase. It was supposed that 4-6 days after aorta coarctation, intracellular regulators (invertors) activating Na,K-ATPase and Ca-ATPase of rat sarcolemma were synthesized in cytosol of adult animals. Invertors activating Na,K-ATPase did not appear after the aorta coarctation in old animals, but factors activating Ca2+-ATPase appeared. Cytosol of adult experimental rats activated Na,K-ATPase of sarcolemmas of cardiomyocytes of intact old animals. The data proved the ability of Na,K-ATPase of sarcolemma of old animals to respond to regulating factors. Based on the divergence between the results of experiments with the Na,K-ATPase and Ca-ATPase activities in old rats, it can be supposed that we were dealing with two different invertors.     

Regulation of the nucleotide dependence of the cardiac sarcolemma Ca(2+)-ATPase.

The nucleotide dependence of the Ca(2+)-ATPase purified from cardiac sarcolemma by calmodulin-affinity chromatography was investigated for preparations either in the basal state or activated by three procedures: (i) addition of calmodulin; (ii) addition of phosphatidylserine and (iii) controlled proteolysis. Upon activation, the maximal velocity of ATP hydrolysis increases by a factor of 4-5, while the curves of ATP dependence of ATP hydrolysis change from hyperbolic to biphasic, revealing the presence of two Kmapp for ATP. A tight coupling between Ca2+ and ATP binding sites was also observed. At high ATP concentration, the ATPase activity of the basal state shows a complex dependence on Ca2+ concentration, increasing sharply at millimolar Ca2+. Our results indicate that this increase in ATPase activity is paralleled by the appearance of a second, low affinity Kmapp for ATP. When only the high affinity site for ATP is occupied the ATPase activity of the basal state displays a simple, hyperbolic dependence on the Ca2+ concentration. In addition, increasing Ca2+ concentration appears to decrease the ATP binding at the low affinity site of the enzyme. The effect of ADP on ATP hydrolysis was also examined. The finding that ADP is a potent inhibitor of the purified Ca(2+)-ATPase from heart suggests that the stimulatory action of ADP observed in cardiac sarcolemmal vesicles is not an intrinsic property of the enzyme.     

Alterations of ultrastructures and anionic sites in basement membranes of myocardial cells and capillaries in patients with cyanotic congenital heart disease due to tetralogy of Fallot

Electron microscopic cytochemical studies of the basement membranes of myocardial cells and capillaries were performed in 13 patients with tetralogy of Fallot who were divided into 2 groups. Group 1 included 7 patients in the early stage of the disease, ranging in age from 7 months to 5 years. Group 2 consisted of 6 patients in the far advanced stage of the disease, ranging in age from 30 to 46 years. The operatively excised infundibular muscles of the right ventricle were prepared for conventional electron microscopy and electron microscopic cytochemistry. The anionic sites in the basement membranes were characterized by cationic polyethyleneimine. The basement membrane ultrastructures of the myocardial cells and capillaries in the early stage of tetralogy of Fallot showed no apparent alterations with regular distribution of anionic sites, particularly in the external lamina of the basement membranes. In contrast, irregular thickening, wide splitting and lamination of the basement membranes of myocardial cells and capillaries, always associated with derangement and focal loss of anionic sites in the membranes were consistently observed in the far advanced stage of tetralogy of Fallot. The aforementioned results suggest that altered surface membrane integrity of myocardial cells and capillaries resulting from pathologic changes of the basement membranes are an important pathogenetic mechanism responsible for progressive degeneration of infundibular muscle cells and myocardial dysfunction in the course of tetralogy of Fallot.