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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The short-time autolysis of hearts was regarded as a model of ischaemic heart failure. Therefore, isolated rat hearts were subjected to 30--120 min autolysis in a Locke solution at 37 degrees C. Electron microscopic examinations and myofibrillar preparations were made from the autolysed heart ventricles. The myofibrillar proteins were resolved by SDS-polyacrylamide gel electrophoresis. After 30 min autolysis the amount of a protein of 192,000 daltons greatly increased. At the same time on the electron micrographs the focal destruction of filament destruction on the A filament area and the mitochondrial structure altered too. After 60 min autolysis another protein of 36,400 daltons appeared. On the electron micrographs the focal desintegration of Z membranes and the focal destruction of I filaments can be observed. After 120 min autolysis further proteolytic products could not be detected by gel electrophoresis but on the electron micrographs the destruction of Z membranes and I filaments became more pronounced.
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PMID:Investigation of the short-time autolysis of rat hearts by means of SDS. Polyacrylamide gel electrophoresis and electron microscopy. 49 22

The expression of troponin T, a thin filament regulatory protein, was examined in normal and failing left ventricles. The samples were obtained from the hearts of patients with severe heart failure who were undergoing cardiac transplantation, and from normal adult hearts that could not be used for transplantation. Western blots of the myofibrillar proteins demonstrated two isoforms, troponin T 1 (TnT1) and troponin T 2 (TnT2). TnT2 is expressed at significantly higher levels in failing hearts (p less than 0.004). Western blots of two-dimension SDS-PAGE gels resolved two dominant spots of TnT1 and of TnT2 and several minor troponin T species. Alkaline phosphatase treatment markedly decreased the sizes of the two acidic spots while increasing the two more basic spots by a comparable amount. Myofibrillar ATPase activity had an inverse and negative linear relationship (r = 0.7, p less than 0.02) with the myofibrillar percentage of total troponin T comprised of TnT2. In that heart failure in these transplant patients had multiple bases, we propose that rather than a cause of heart failure, the disease-associated changes in troponin T isoform expression are an adaptation to abnormal myocardial function.
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PMID:Troponin T isoform expression in the normal and failing human left ventricle: a correlation with myofibrillar ATPase activity. 138 29

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.
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PMID:Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. 887 78

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure.
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PMID:Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure. 928 60

Alterations in troponin T (TnT) isoforms have been reported in severe human and experimental heart failure (HF), and may play a role in the depressed myofibrillar ATPase activity observed in this condition. It is unclear whether these alterations reflect very severe hemodynamic derangement or are a component of mild hypertrophic stress. Therefore, we studied the expression of TnT isoforms (SDS-PAGE, Western blots), myosin isoforms, myofibrillar ATPase activity, and left ventricular (LV) mechanoenergetics (rbc perfused, isovolumically contracting isolated heart) in a rabbit model of mild hypertrophy (LVH) due to gradual hypertension caused by 12 weeks of cellophane wrap of the kidneys (n=12). LV/body weight ratio increased by 28% in LVH compared to shams (P<0.001); no animals had evidence of HF. In LVH, the percentage of TnT2 was modestly but significantly increased compared to shams [6.2+/-1.9 (+/-S.D. ) v 3.7+/-1.0%, P<0.05], mainly as a consequence of a parallel decrease in TnT4 (P=0.07). Sham hearts ranged from 75-100% V3 isomyosin, whereas all LVH hearts had 100% of the V3 form. There were no significant differences in myofibrillar ATPase activity or mechanical variables, including contraction and relaxation rates. The slope of the VO2-pressure-volume-area relation (a measure of the energy conversion efficiency of the contractile machinery) was also unchanged. We conclude that in the rabbit, shifts in TnT isoforms toward a more "fetal" pattern occur during mild LVH and, therefore, are likely to be a general feature of the response to hemodynamic stress, rather than a phenomenon confined to end-stage disease. These modest shifts are not associated with major alterations in LV myofibrillar ATPase activity or mechanoenergetics.
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PMID:Altered expression of troponin T isoforms in mild left ventricular hypertrophy in the rabbit. 929 58

The tumor necrosis factor (TNF) alpha level is elevated in patients with advanced heart failure, and the phosphorylation of contractile regulatory proteins is reduced in the human heart. We hypothesized that TNFalpha affects the phosphorylation of proteins involved in regulating contraction; phospholamban (PLB), myosin light chain 2 (MLC2) and troponin I (TnI). Spontaneously beating rat neonatal cardiac myocytes, prelabelled with [32P]orthophosphate, were treated with TNFalpha for 30 min, and stimulated with isoproterenol for 5 min. 32P-labelled myofibrillar proteins were isolated by 15% SDS-PAGE. Baseline phosphorylation levels of PLB, TnI and an unknown 23kDa phosphoprotein were decreased by TNFalpha in a dose-dependent manner. Moreover, TNFalpha attenuated the phosphorylation levels of PLB and TnI increased by a concentration of 0.01 microM isoproterenol, but not by 1 microM of isoproterenol. Although TNFalpha had no effect on the cAMP content or cAMP-dependent protein kinase activity in the presence or absence of isoproterenol, an inverse relationship was observed between the concentration of TNFalpha and the cGMP content in cardiac myocytes, and treatment with TNFalpha resulted in a concentration-dependent increase in type 2A protein phosphatase activity. The observation that TNFalpha decreases phosphorylation levels of PLB and TnI in cardiac myocytes suggests that the reduction of these protein phosphorylation levels is partially responsible for alterations of intracellular Ca2+-cycling and the force of contraction in TNF alpha-treated cardiac myocytes. Furthermore, TNFalpha reduces myocyte contraction and protein phosphorylation states possibly via cAMP-independent mechanisms, at least in part, by the activation of type 2A protein phosphatase.
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PMID:Tumor necrosis factor-alpha decreases the phosphorylation levels of phospholamban and troponin I in spontaneously beating rat neonatal cardiac myocytes. 1007 33

The present study examines ultrastructural and molecular changes in ventricular myocardium associated with ascites cases in fast-growing broilers raised at low altitude. Extensive ultrastructural lesions were seen in the left and right ventricular myocardium of broilers with fulminant heart failure and ascites. Significant changes included lesions in the myofibril contractile apparatus, altered mitochondria, marked reduction in the myofibril component, and changes in the extracellular matrix (ECM) architecture. No lesions were observed in hearts of slow growing broilers, but mild to moderate changes (predominantly in the left ventriculum) were apparent in the hearts from some clinically normal, fast-growing broilers. SDS-PAGE profiles of washed myofibrils showed several distinctly different bands in preparations from left ventricular myocardium of ascitic birds. Western blot analysis of these samples revealed several fragments of myosin heavy chain, M-protein, and titin. Based on gelatinolytic activity, matrix metalloproteinases (MMP) in the cytosolic fraction of ventricular myocardium homogenates were identified as MMP-2. The relative activity of this enzyme appears to be considerably higher in preparations from broilers, particularly in the preparations from the left ventriculum of fast-growing broilers, in comparison to leghorns or slow growing broilers. The nature and distribution of the changes in the heart indicate that chronic cardiomyopathic process in the left ventricular myocardium occurs during the development of ascites. It is postulated that progressive deterioration of the left heart pump function caused by initial lesions in the left ventricular myocardium is a significant factor in the development of pulmonary hypertension and the pathogenesis of ascites in broilers raised at low altitude.
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PMID:Ultrastructural and molecular changes in the left and right ventricular myocardium associated with ascites syndrome in broiler chickens raised at low altitude. 1151 7

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts. To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17 +/- 4 microg hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8 +/- 2.3 to 45.1 +/- 3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7 +/- 89.8 to 2,181 +/- 135.4 mmHg/s in the contraction rate, and 713 +/- 60.2 to 1,364 +/- 137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.
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PMID:Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model. 1498 54

Isometric force production and ATPase activity were determined simultaneously in single human skeletal muscle fibers (n = 97) from five healthy volunteers and nine patients with chronic heart failure (CHF) at 20 degrees C. The fibers were permeabilized by means of Triton X-100 (1% vol/vol). ATPase activity was determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. Calcium-activated actomyosin (AM) ATPase activity was obtained by subtracting the activity measured in relaxing (pCa = 9) solutions from that obtained in maximally activating (pCa = 4.4) solutions. Fiber type was determined on the basis of myosin heavy chain isoform composition by polyacrylamide SDS gel electrophoresis. AM ATPase activity per liter cell volume (+/-SE) in the control and patient group, respectively, amounted to 134 +/- 24 and 77 +/- 9 microM/s in type I fibers (n = 11 and 16), 248 +/- 17 and 188 +/- 13 microM/s in type IIA fibers (n = 14 and 32), 291 +/- 29 and 126 +/- 21 microM/s in type IIA/X fibers (n = 3 and 5), and 325 +/- 32 and 205 +/- 21 microM/s in type IIX fibers (n = 7 and 9). The maximal isometric force per cross-sectional area amounted to 64 +/- 7 and 43 +/- 5 kN/m(2) in type I fibers, 86 +/- 11 and 58 +/- 4 kN/m(2) in type IIA fibers, 85 +/- 6 and 42 +/- 9 kN/m(2) in type IIA/X fibers, and 90 +/- 5 and 59 +/- 5 kN/m(2) in type IIX fibers in the control and patient group, respectively. These results indicate that, in CHF patients, significant reductions occur in isometric force and AM ATPase activity but that tension cost for each fiber type remains the same. This suggests that, in skeletal muscle from CHF patients, a decline in density of contractile proteins takes place and/or a reduction in the rate of cross-bridge attachment of approximately 30%, which exacerbates skeletal muscle weakness due to muscle atrophy.
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PMID:Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure. 1605 11

A two-dimensional gel electrophoresis (2-DE)-based proteomic approach was used to study a transgenic mouse model of acerbated dilated cardiomyopathy in which the small monomeric GTPase, Rac1, was constitutively expressed exclusively in the myocardium. A subfractionation procedure allowed for the focused analysis of both cytoplasmic and myofilament protein-enriched extracts of ventricular tissue from Rac1 transgenic and age-matched nontransgenic (NTG) mice. The majority of these mice displayed severe hypertrophy (heart-to-body weight ratios >2-fold greater in the Rac1 mice) and died from overt heart failure between days 14 and 17. Comparative 2-DE analysis (pH 3-10, 12% SDS-PAGE) derived from Rac1 (n = 4) and NTG (n = 4) groups revealed differences in mean protein spot intensities. Twelve proteins from the cytoplasmic protein-enriched extract met our criteria for robustness and spot resolution and were identified. These proteins represent a broad distribution of cellular functions with only some previously implicated in myocardial hypertrophy. The myofilament subproteome displayed no change in posttranslational modification, but further analysis by one-dimensional Western blot showed increased quantities of myofilament proteins in the Rac1 mouse ventricles. Additionally, three proteins with different functionality that were altered in the cytoplasmic protein-enriched subproteome, tubulin beta-chain, manganese superoxide dismutase, and malate dehydrogenase, were analyzed at days 7, 9, and 11 to assess their role in the development of the dilated cardiomyopathic phenotype. The quantity of all three proteins peaked at day 9, suggesting an early response in cardiac hypertrophic failure.
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PMID:Myocardial subproteomic analysis of a constitutively active Rac1-expressing transgenic mouse with lethal myocardial hypertrophy. 1615 95


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