Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle

This study tested the hypothesis that with hypertrophy, the proportion, distribution, and structural alignment of fibrillar collagen are important determinants of myocardial stiffness. Toward this end, the collagen volume fraction (morphometry), the transmural or subendocardial distribution of collagen, and the structural arrangement of fibrillar collagens (picrosirius red) were examined in the hypertrophied ventricle secondary to pressure overload (abdominal aorta banding or perinephritis), isoproterenol, and pressure overload plus isoproterenol. In the same hearts, the slopes of the systolic and diastolic stress-strain relations of the left ventricle, representing its active and passive stiffness, respectively, were obtained. In comparison with controls, we found 1) for a moderate rise in transmural collagen, active and passive stiffness increased with pressure-overload hypertrophy; 2) following isoproterenol alone there was a marked increase in subendocardial collagen, and active and passive stiffness increased; 3) in pressure-overload hypertrophy plus isoproterenol, active stiffness declined. Passive stiffness was increased except when fibrosis and thinning of the interventricular septum occurred, in which case it decreased; and 4) fibrillar collagens involved in remodeling included the formation of either collagen strands and fibers in a greater number of previously collagen-free intermuscular spaces in pressure-overload hypertrophy, or a dense crisscrossing latticework of fibers that encircled muscle fibers after isoproterenol. Thus, an increase in fibrillar collagen in pressure-overload hypertrophy is partially adaptive in that it enhances the tensile strength and three-dimensional delivery of force by the myocardium, but at the expense of reducing distensibility. The appearance of a dense collagen meshwork within the subendocardium after isoproterenol can be considered pathological in that it entraps muscle fibers causing active stiffness to fall while impairing distensibility. Finally, fibrosis may paradoxically reduce passive stiffness if it leads to a thinning of the interventricular septum.     

Influence of primary coronary intervention on myocardial collagen metabolism and left ventricle remodeling predicted by collagen metabolism markers

The aims of the present study were to analyze cardiac collagen metabolism changes in vivo during acute and nonacute phases of ST elevation myocardial infarction (STEMI) in patients who were treated with primary coronary intervention (PCI) only, and to determine the predictive significance of collagen I and III synthesis markers (PICP, PIIINP) as well as the collagen I degradation marker (ICTP) on left ventricular function and volume changes after STEMI. Serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) assessed on the 30th day and the carboxyterminal telopeptide located at the C end of collagen type I (ICTP) assessed on the 7th day after STEMI were significantly higher (P = 0.01, P = 0.019, P = 0.04, respectively) in the PCI unsuccessful group than in the PCI successful group. These findings support the theory that early and successful PCI not only limits the amount of muscle necrosis but also protects cardiac collagen from ischemia-related injury. PICP and PIIINP levels assessed on the fourth day after acute STEMI enables us to predict the development of left ventricular function (EF) and end-diastolic volume changes over the course of 6 months, irrespective of the initial EF or revascularization success.     

左室重构研究

目的 探讨心肌梗死后心室重构的规律,进一步阐明心肌梗死后心脏功能减退的机制,为心肌缺血损伤的合理治疗提供理论依据.方法 27只中国小型猪,体重为20 kg,随机分成实验组(12只)及对照组(15只).结扎LAD,建立标准化急性心肌梗死动物模型.LAD结扎前、手术当天及术后5周后分别进行心脏磁共振检查及血流动力学监测,取出心脏标本,将左心室分成17段,进行分段病理观察.结果 死亡率:实验组为16.7％(2/12),对照组为33.3％(5/15).实验组及对照组心肌梗死体积变异[(484.22±225.88)mm3比(2986.34±1937.13 )mm3,P=0.0043]、左心室射血分数(EF值)及dp/dt maximum的变异差异有统计学意义(P＜0.05).实验组dp/dt:Max( 1546.67±477.89 )mm Hg/s比(973.77±208.12)mm Hg/s,P=0.004922;左心室内压:SBP(75.56±12.59)mm Hg比(59.03±6.93)mm Hg,P=0.000753,DBP(6.56±3.14)mm Hg比(4.22±1.41)mm Hg,P=0.03113.LAD结扎前与结扎后5周比较,差异显著.磁共振结果显示,LAD结扎前后,心脏收缩末期梗死区周围室间隔最大厚度[(5.32±1.10)mm比(7.5±0.78)mm,P=0.001]及心室侧壁心肌最大厚度[(5.57±1.05)mm比(7.93±1.62)mm,P=0.001]差异显著.LAD结扎5周后,对左心室17段心肌的病理观察表明,全部17段心肌内均存在大小不等的梗死灶.结论 局部心肌梗死可引发左心室全部17段心肌内出现梗死灶;非缺血性梗死的多米诺效应及第二左心室的形成、扩大与消失,是心肌梗死后心室重构的重要特征.     

Perioperative hemodynamic and geometric changes of the left ventricle during cardiomyoplasty in goats with dilated left ventricle

OBJECTIVE: Clinical data have suggested the occurrence of temporary short-term deterioration of the heart following cardiomyoplasty. The purpose of this study was to monitor the short-term hemodynamic effects of cardiomyoplasty in a goat model of a dilated left ventricle, using conductance catheters (ie, pressure-volume loops) and cardiac output measurements. METHODS: Eight female goats underwent acute cardiomyoplasty 8 to 12 weeks after left ventricular (LV) dilatation was induced by a carotid jugular arteriovenous shunt. The cardiomyoplasty procedure was monitored using a Swan-Ganz catheter for cardiac output measurements and a 12-electrode (dual-field) conductance catheter to LV pressure-volume loops. RESULTS: After wrapping the heart with the latissimus dorsi muscle, there was a significant reduction in both cardiac output and LV end-diastolic volume (LVEDV) at 10 min. Partial recovery was observed 45 min later. CONCLUSION: A decrease in both cardiac output and LVEDV was observed following myocardial wrapping. This may explain some of the perioperative and postoperative morbidity and mortality observed following cardiomyoplasty.     

The mechanism of mitral regurgitation in dilated left ventricle

To assess the mechanism of mitral regurgitation in ventricular dilatation, 24 patients with dilated cardiomyopathy (13 with and 11 without mitral regurgitation) and 10 normal individuals were studied by two-dimensional echocardiography. Left ventricular dimensions and mitral ring diameters in systole and diastole were measured in the long-axis section, and systolic interpapillary muscle distance in the short-axis section. The results showed: (1) Mitral ring diameter is increased in most patients with dilated cardiomyopathy. (2) Neither increased ring diameter, reduced ring contraction, nor decreased interpapillary muscle distance determine the presence of mitral regurgitation. (3) The only difference between those patients with and without mitral regurgitation was the degree of left ventricular dilatation (p<0.05).     

缬沙坦对压力超负荷下兔左室心肌TNF-α表达及胶原重构的影响

目的 :观察缬沙坦 （Valsartan）对慢性压力超负荷下左室心肌 TNF-α表达、胶原重构及心功能的影响。方法 :家兔 3 0只随机分为假手术组、腹主动脉次全结扎组 （简称结扎组 ）、缬沙坦干预结扎组 （简称干预组 ） ,每组 10只。术后 12周进行血流动力学检查并取左室心肌行 VG染色及免疫组化染色分别观察胶原容积百分比 （CVF）及TNF-α表达情况。结果 :结扎组与假手术组比较 ,TNF-α表达显著增强 （P<0 .0 1） ,左室质量 /体质量 （L VW/BW）、左室舒张末压 （L VEDP）、含小血管视野的 CVF（CVF-V）及不含小血管视野的 CVF（CVF-NV）均显著升高 （均 P<0 .0 1） ;缬沙坦干预组与结扎组比较 ,TNF-α表达显著减弱 （P<0 .0 1） ,L VW/BW、L VEDP、CVF-V,CVF-NV显著降低 （均 P<0 .0 1）。结论 :缬沙坦可抑制压力负荷下心室肌 TNF-α的过度表达并减轻心室肌的胶原增生、心室重构及心功能的损害     

Characterization of intramuscular collagen in the mammalian left ventricle

Summary Left ventricular collagen of various mammals (cat, cow, dog, pig, and rat) was successively extracted with neutral salt, and dilute acid solutions, and limited pepsin digestion. The distribution of the various types of collagen molecules in pepsin-solubilized ventricular collagen was analyzed electrophoretically on SDS-polyacrylamide gels in the presence of 3.6 M urea.Yields of dilute-acid-soluble collagen were only 0.4 to 0.6% of the total ventricular collagen, and less than 0.1% with neutral salt solution. Approx. 55–90% of the total collagen was extracted by limited pepsin digestion.Disc patterns of pepsin-soluble collagen revealed the presence of dimeric and trimeric components, as well as higher-molecular-weight aggregates in all samples of nonreduced and reduced ventricular collagen. Taken together, these findings suggest the presence of an extensive interchain and intermolecular cross-linking network in left ventricular collagen.Comparison of electrophoretical disc gel patterns of reduced and nonreduced pepsin-solubilized collagen indicated that left ventricular collagen is heterogenous in nature, consisting of a mixture of type I and type III collagen. It was evident that primarily type I components occur in ventricular collagen. The components of type III collagen molecules occurred in all investigated left ventricles in varying and consistently appreciably lower amounts. The proportions of type III and type I collagen vary in left ventricular tissue of different species.Supported by grants from the Deutsche Forschungsgemeinschaft     

慢性压力超负荷兔左室心肌细胞电重构与结构重构发生的非同步性

目的探讨慢性压力超负荷兔中层心室肌细胞电重构与结构重构发生的非同步性及其意义。方法新西兰兔64只,随机分为缩窄组和假手术组,采用肾上腹主动脉缩窄术制备兔左室压力超负荷模型。术后2周和8周胶原酶两步消化法分离获取左室中层单个心肌细胞,应用激光扫描共聚焦显微镜技术测定中层细胞体积和蛋白含量,全细胞膜片钳技术记录中层细胞膜电容、动作电位(AP)。结果与假手术组比较,术后2周缩窄组中层细胞体积、蛋白含量及膜电容无明显改变,但基础刺激周长(BCL)为2 s时,缩窄组AP复极达90%时程(APD90)较假手术组延长13.7%(P<0.05);与假手术组比较,术后8周缩窄组中层细胞体积、蛋白含量及膜电容分别增加28.0%、38.3%、34.0%(P<0.05或0.01),APD90延长30.6%(P<0.01)。术后2周和8周,与假手术组比较,缩窄组中层细胞APD呈现更明显的频率依赖性,且更易发生早期后除极(BCL=2 s,EAD)。结论左室慢性压力超负荷过程中,中层心肌细胞电重构的发生明显早于结构重构,且可能具有潜在致心律失常危险。     

Progression of hypertrophic into a dilated left ventricle in Friedreich's ataxia

The authors describe the case of a girl who developed Friedreich's ataxia at, approximately, the age of 7, with evidence of cardiac involvement being detected by electrocardiography and echocardiography at a later date. Cardiac function was moderately impaired and remained unchanged for a number of years, during which a picture of hypertrophic left ventricle seemed to be firmly established. Later still, however, the cardiac situation shifted gradually toward a hypokinetic form of the disease, with a progressive thinning of the interventricular septum and posterior wall of the left ventricle, associated enlargement of the ventricular chambers and increasingly severe hypokinesia leading to repeated episodes of heart failure.     

Reverse remodeling during long-term mechanical unloading of the left ventricle

A significant proportion of patients placed on long-term mechanical circulatory support for end-stage heart failure can be weaned from mechanical assistance after functional recovery of their native heart ("bridge to recovery"). The pathophysiological mechanisms implicated in reverse remodeling that cause a sustained functional myocardial recovery have recently become the subject of intensive research, expected to provide information with a view to accurately identify reliable prognostic indicators of recovery. In addition, this kind of information will enable changes in the strategy of myocardial recovery by modifying the duration and scale of the unloading regimen or by combining it with other treatments that promote reverse remodeling.     

Diastolic viscous properties of the intact canine left ventricle

The viscoelastic model of the ventricle predicts that the rate of change of volume (strain rate) is a determinant of the instantaneous pressure in the ventricle during diastole. Because relaxation is not complete before the onset of filling, one cannot distinguish the individual effects of relaxation and viscosity unless the passive and active components that determine the ventricular pressure are separated. To overcome this problem, we used the method of ventricular volume clamping to compare the pressures in the fully relaxed ventricle at a given volume at zero strain rate (static pressure) and high strain rate (dynamic pressure). Six open-chest, fentanyl-anesthetized dogs were instrumented with micromanometers and an electronically controlled mitral valve occluder in series with the electromagnetic flow probe. We reasoned as follows: If there were significant viscosity, then the dynamic pressure would be higher than the static pressure. The static pressure was measured when the ventricle was completely relaxed following a mitral valve occlusion after an arbitrary filling volume had been achieved. The dynamic pressure was determined by delaying the onset of filling until relaxation was complete and then measuring the pressure at the same volume that was achieved when the static pressure was measured. In 19 different hemodynamic situations, the dynamic and static pressures were identical (mean difference, 0.1 +/- 0.8 mm Hg), indicating that in the passive ventricle viscoelastic effects are insignificant and do not contribute to the left ventricular diastolic pressure under normal filling rates.     

Early and late remodeling of the left ventricle after acute myocardial infarction

This report describes early and later structural changes that occur in infarcted and noninfarcted ventricular myocardium after coronary arterial ligation in the rat. Histologic analysis was conducted of hearts subjected to 2 days (n = 22) and 21 days (n = 22) of coronary arterial occlusion, or to a sham operation (n = 22). Lengths, circumferences and areas of the left ventricle, of infarcted myocardium and of noninfarcted myocardium were obtained by videoplanimetry. Although the left ventricular (LV) endocardial circumference was similarly increased at 2 days (19 +/- 3 mm, mean +/- standard deviation) and 21 days (20 +/- 3 mm) compared with shams (13 +/- 3 mm, p less than 0.01), LV epicardial circumference was similar in all 3 groups (30 +/- 2, 31 +/- 2 and 31 +/- 2 mm, respectively). The area enclosed by the endocardial circumference was significantly (p less than 0.01) increased at 2 days (20 +/- 6 mm2) and 21 days (22 +/- 6 mm2) compared with shams (7 +/- 4 mm2); however, the area enclosed by the epicardial circumference was similar at 2 days, 21 days and in shams (70 +/- 9, 72 +/- 9 and 73 +/- 10 mm2, respectively). The total LV tissue area was similar at 2 and 21 days, but was less than that in shams (p less than 0.01). Between 2 and 21 days, 3 measures of infarcted myocardium significantly decreased: its segments of endocardial and epicardial circumference, its circumference and its area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transmural myocardial deformation in the ischemic canine left ventricle

The myocardium is a complex three-dimensional structure consisting of myocytes interconnected by a dense collagen weave that courses in different directions. Regional ischemia can be expected to produce complex changes in ventricular deformation. In the present study, we examined the effects of ischemia on two- and three-dimensional finite strains during acute transmural myocardial ischemia in 13 open-chest anesthetized dogs. In contrast to systolic deformation observed during the control period in which circumferential shortening exceeded longitudinal shortening, our results indicate that after 5 minutes of acute ischemia, end-systolic in-plane lengthening across the left ventricular wall occurs in approximately equal amounts in the circumferential and longitudinal directions. Along with these changes in extensional strains, there were significant negative transverse shearing deformations during ischemia. Myocardial ischemia also resulted in a loss of the normal end-systolic transmural gradients of shortening and thickening. Three-dimensional end-diastolic strains indicate that the left ventricular wall undergoes a significant passive reconfiguration that varies transmurally with lengthening in the epicardial tangent plane and wall thinning increasing from the epicardium toward the endocardium. The large systolic changes in shearing deformations with ischemia could potentially influence collateral blood flow and certainly indicate that uniaxial measurements of deformation in the ischemic myocardium, which do not account for shearing deformation, are incomplete and must be interpreted with caution. Moreover, normal transmural systolic gradients in deformation, which would be anticipated on geometric grounds, are lost during ischemia, implying that the material properties of ischemic tissue or the loading conditions imposed on the ischemic region by partially impaired adjacent myocardium vary transmurally.     

Characterization of subfractions from purified sarcolemma of canine left ventricle

Three membrane fractions were studied from canine myocardial left ventricle (LV); crude, light vesicle, and enriched sarcolemma. The percent of the total yield of membrane protein was 99.3 +/- 0.2% for the crude fraction, 0.4 +/- 0.1% for the light vesicle fraction, and 0.3 +/- 0.03% for the purified fraction. Sodium, potassium-ATPase activity in the purified fraction (100 +/- 10.8 mumol Pi/h/mg) was five fold more concentrated than in the light vesicle fraction (18.5 +/- 1.85 mumol Pi/h/mg), and nineteen fold more than in the crude fraction (5.29 +/- 0.57 mumol Pi/h/mg). beta-Adrenergic receptors were 8-fold enriched in the purified fraction (1006 +/- 219 vs 132 +/- 13 fmol/mg in the crude fraction) and 4-fold enriched in the light vesicle fraction (497 +/- 152 fmol/mg). Adenylate cyclase activity was enriched by only 13 to 17-fold in the purified fraction, and only 2 to 4-fold in the light vesicle fraction. The percent of the total beta-adrenergic receptors per gram wet weight was 94 +/- 20% for the crude fraction, 2.1 +/- 0.4% for the light vesicle fraction, and 3.8 +/- 0.7% for the purified fraction. When alamethicin was used to uncover latent enzyme activity, beta-adrenergic receptor density was not affected, but Na+,K(+)-ATPase and adenylate cyclase activity were enhanced in each membrane fraction studied. The surprising finding was that Na+,K(+)-ATPase activity was enriched to the same extent as the beta-adrenergic receptor density in the light vesicle fraction. One potential explanation is that the light vesicle fraction is located in a specialized region of the plasma membrane.     

Response of the left ventricle in idiopathic dilated cardiomyopathy to postextrasystolic potentiation

The effectiveness of postextrasystolic potentiation (PESP) was assessed to detect residual function of the left ventricle in seven patients with idiopathic dilated cardiomyopathy (IDC). The postextrasystolic changes in the aortic pressure pulse, global left ventricular function, and quantitative regional left ventricular wall motion were investigated. PESP caused an increase in the peak systolic aortic pressure (116 +/- 17 to 130 +/- 25 mm Hg, p less than 0.01), a decrease in the peak diastolic aortic pressure (74 +/- 12 to 61 +/- 11 mm Hg, p less than 0.001), a decrease in preejection period/left ventricular ejection time (PEP/LVET) ratio (0.637 +/- 0.136 to 0.457 +/- 0.097, p less than 0.001), and an increase in the global left ventricular ejection fraction (LVEF) (0.26 +/- 0.09 to 0.40 +/- 0.12, p less than 0.01). Postextrasystolic changes in LVEF were inversely related to changes in PEP/LVET (r = -0.76, p less than 0.05). The postextrasystolic patterns of the regional wall motion of the left ventricle were different in each patient. The results of this study suggest that residual left ventricular function can be detected in patients with IDC by their response to PESP.     

牛磺酸对扩张型心肌病大鼠心肌胶原重塑的影响

目的:探讨牛磺酸对呋喃唑酮扩张型心肌病(DCM)大鼠左室心肌胶原重塑的影响及其机制。方法:将60只大鼠分为3组,即正常对照组(C组)、DCM模型组(D组)和牛磺酸治疗组(T组),每组20只,C组按常规饲养,D组在饮水中加呋喃唑酮饲养,T组除加呋喃唑酮饲养外同时注射牛磺酸,饲养4周和8周后分2批经超声心动图检测大鼠心功能,测量大鼠左室内径和左室游离壁厚度;苏木精-伊红和VG染色分别观察大鼠心肌细胞和间质胶原纤维的变化;免疫组化和RT-PCR检测左室心肌基质金属蛋白酶1(MMP1)和基质金属蛋白酶组织抑制因子1(TI MP1)表达水平。结果:D组大鼠左心室内径增大、游离壁变薄,左室收缩功能下降;间质纤维明显增生;左室心肌MMP1表达水平明显上调及TI MP1表达水平明显下调。而T组大鼠左室结构和功能正常,心肌间质胶原无明显增生,MMP1表达水平明显下调及TI MP1表达水平明显上调。结论:牛磺酸能抑制呋喃唑酮DCM大鼠左室心肌胶原重塑,其机制可能是通过调节MMP1与TI MP1的平衡而起作用。