Electron microscopic investigation of endomyocardial biopsy samples in hypertrophy and cardiomyopathy. A semiquantitative study in 48 patients.

Baandrup, Ulrik; Florio, R; Roters, Francisco Augusto; Olsen, E. G. J.

doi:10.1161/01.cir.63.6.1289

Cited by 95 publications

(40 citation statements)

References 30 publications

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“…No relationship between morphological changes and cardiac functional status has been identified (40). These studies, however, were performed before the availability of genotype analysis for FHC; thus, no information is currently available regarding allele-or gene-specific ultrastructural findings.…”

Section: Discussionmentioning

confidence: 99%

Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

et al. 1999

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Multiple mutations in cardiac troponin T (cTnT) can cause familial hypertrophic cardiomyopathy (FHC). Patients with cTnT mutations generally exhibit mild or no ventricular hypertrophy, yet demonstrate a high frequency of early sudden death. To understand the functional basis of these phenotypes, we created transgenic mouse lines expressing 30%, 67%, and 92% of their total cTnT as a missense (R92Q) allele analogous to one found in FHC. Similar to a mouse FHC model expressing a truncated cTnT protein, the left ventricles of all R92Q lines are smaller than those of wild-type. In striking contrast to truncation mice, however, the R92Q hearts demonstrate significant induction of atrial natriuretic factor and β-myosin heavy chain transcripts, interstitial fibrosis, and mitochondrial pathology. Isolated cardiac myocytes from R92Q mice have increased basal sarcomeric activation, impaired relaxation, and shorter sarcomere lengths. Isolated working heart data are consistent, showing hypercontractility and diastolic dysfunction, both of which are common findings in patients with FHC. These mice represent the first disease model to exhibit hypercontractility, as well as a unique model system for exploring the cellular pathogenesis of FHC. The distinct phenotypes of mice with different TnT alleles suggest that the clinical heterogeneity of FHC is at least partially due to allele-specific mechanisms.

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Section: Discussionmentioning

confidence: 99%

Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

et al. 1999

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“…5 Based on these hallmarks, the nuclei were nuclei were evaluated per specimen and the mean value of the scoring was determined as the nuclear hypertrophy score of the electron microscopic specimen. Similarly, nuclear hypertrophy was scored as 0-3 using the paraffin-sections stained with hematoxylin-eosin under light microscopy based on the degree of nuclear deformity and the thickness of the hematoxylin stain of nuclear chromatin (Fig 2A).…”

Section: Scoring Of Nuclear Hypertrophy By Electron and Light Microscopymentioning

confidence: 99%

“…The nuclear change has been well characterized as "hypertrophied nucleus" by the morphological hallmarks of severe crenation of the nuclear membrane (bizarre shape) and widespread clumping of chromatin. [3][4][5] However, the significance of such dramatic alteration of the nuclear phenotype in hypertrophic hearts is largely unknown. We previously reported that hypertrophied nuclei in the myocytes of human hearts with dilated cardiomyopathy (DCM) were accompanied by increased activity of DNA repair/synthesis.…”

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confidence: 99%

Nuclear Hypertrophy Reflects Increased Biosynthetic Activities in Myocytes of Human Hypertrophic Hearts

Koda

Takemura

Okada

et al. 2006

Circ J

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n response to various stresses, cardiac myocytes present phenotypic alterations of the cytoplasm, such as increased cell volume, increased fraction of subcellular organelles in contrast to decreased fractions of myofilaments, mitochondriosis, and intracytoplasmic vacuoles. 1,2 Nuclear structure is markedly altered as well. The nuclear change has been well characterized as "hypertrophied nucleus" by the morphological hallmarks of severe crenation of the nuclear membrane (bizarre shape) and widespread clumping of chromatin. [3][4][5] However, the significance of such dramatic alteration of the nuclear phenotype in hypertrophic hearts is largely unknown. We previously reported that hypertrophied nuclei in the myocytes of human hearts with dilated cardiomyopathy (DCM) were accompanied by increased activity of DNA repair/synthesis. 6 Scholz et al speculated that the nuclear abnormalities might be the primary event in the pathogenesis of DCM and that they might lead to a reduced transcriptional rate, which most probably was the cause of the lack of myofilaments and other degenerative changes. 7 However, the molecular biological alterations are largely unknown in the hypertrophied nucleus of various hypertrophic hearts. We hypothesize that such a nuclear phenotype change is associated with various molecular biological alterations occurring in myocyte nuclei of pathologic hearts, which may also be related to cardiac functional alterations. Thus, the major aim of the present study was to use endomyocardial biopsy specimens from hypertrophic hearts of various etiologies to examine linkages between the structural and molecular biological alterations of the hypertrophied nuclei of cardiac myocytes of human hypertrophic hearts. Methods Patients and Endomyocardial BiopsiesThis study was approved by the Institutional Research Committee. A total of 93 patients with hypertrophic hearts were studied (Table 1): DCM (n=23); postmyocarditis (n=13); hypertrophic cardiomyopathy (HCM, n=21); apical hypertrophic cardiomyopathy (APH, n=11); hypertensive heart disease (HHD, n=11); 14 nonhypertrophic hearts served as controls. There were 67 males and 26 females with a mean age of 58±13 years. Echocardiography, cardiac catheterization, and coronary angiography were performed and left ventricular (LV) endomyocardial biopsies were obtained. Measurements included by echocardiography, LV mass index (LVMI); interventricular septal thickness, and LV posterior wall thickness, and by cardiac catheterization, LV end-diastolic volume index, LV ejection fraction (LVEF), and LV end-diastolic pressure. Each endomyocardial biopsy was originally performed for differentiation between primary and secondary myocardial diseases. The Background The nucleus of the myocytes in human hypertrophic hearts is characterized by its bizarre shape and widespread clumping of chromatin. The functional significance has not been determined. Methods and ResultsLeft ventricular (LV) endomyocardial biopsies obtained from patients with dilated cardiomyopathy (DCM, n=23), postmy...

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“…Much less is known about arrhythmia mechanisms in patients with IDC. There is some evidence of disturbed conduction in patients with IDC (2,(5)(6)(7)(8), and there is considerable evidence of abnormal cellular function (9-1 1 ), abnormal passive electrical properties ( 12,13), and abnormal morphologic features that could contribute to abnormal propagation (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However, we are not aware of any previous attempts to systematically examine the spread ofelectrical activity in cardiomyopathic states in humans or in animal models.…”

Section: Introductionmentioning

confidence: 99%

Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy.

Anderson¹,

Walker²,

Urie³

et al. 1993

J. Clin. Invest.

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Myocardial propagation may contribute to fatal arrhythmias in patients with idiopathic dilated cardiomyopathy (IDC). We examined this property in 15 patients with IDC undergoing cardiac transplantation and in 14 control subjects. An 8 X 8 array with electrodes 2 mm apart was used to determine the electrical activation sequence over a small region of the left ventricular surface. Tissue from the area beneath the electrode array was examined in the patients with IDC. The patients with IDC could be divided into three groups. Group I (n = 7) had activation patterns and estimates of longitudinal (OL = 0.84±0.09 m/s) and transverse (OT = 0.23±0.05 m/s) conduction velocities that were no different from controls (OL = 0.80±0.08 m/s, OT = 0.23±0.03 m/s). Group II (n = 4) had fractionated electrograms and disturbed transverse conduction with normal longitudinal activation, features characteristic of nonuniform anisotropic properties. Two of the control patients also had this pattern. Group III (n = 4) had fractionated potentials and severely disturbed transverse and longitudinal propagation. The amount of myocardial fibrosis correlated with the severity of abnormal propagation. We conclude that (a) severe contractile dysfunction is not necessarily accompanied by changes in propagation, and (b) nonuniform anisotropic propagation is present in a large proportion of patients with IDC and could underlie ventricular arrhythmias in this disorder. (J.

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Electron microscopic investigation of endomyocardial biopsy samples in hypertrophy and cardiomyopathy. A semiquantitative study in 48 patients.

Cited by 95 publications

References 30 publications

Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

Nuclear Hypertrophy Reflects Increased Biosynthetic Activities in Myocytes of Human Hypertrophic Hearts

Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy.

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