Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Heart development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1990

[Progressive left ventricular dilatation following anterior myocardial infarct as a determinant for the development of heart failure].

35 consecutive patients were studied prospectively with respect to echocardiographic left ventricular size after anterior myocardial infarction. In 25 patients sufficient follow-up was possible. Another 57 patients and volunteers were examined to prove accuracy in comparison to angiocardiography and nuclear magnetic resonance imaging and reproducibility as well as to define normal values. While two-thirds of all patients did not develop left ventricular dilation, one-third showed marked dilation with left ventricular size being 41% above mean normal value. All patients who subsequently developed congestive heart failure or died were in this group. Two-thirds showed no left ventricular dilation and had an uneventful follow-up. Mean left ventricular dilation for all infarcts was 22% within 4 weeks and 26% within 6.3 months, but some patients showed marked left ventricular dilation beyond 4 weeks. We conclude that serial echocardiography is very useful for stratification of risk for CHF after myocardial infarction, and left ventricular dilation is a major risk factor for CHF.

Adult↗
PubMed2006

Apoptosis in the developing mouse heart.

Apoptosis occurs at high frequency in the myocardium of the developing avian cardiac outflow tract (OFT). Up- or down-regulating apoptosis results in defects resembling human conotruncal heart anomalies. This finding suggested that regulated levels of apoptosis are critical for normal morphogenesis of the four-chambered heart. Recent evidence supports an important role for hypoxia of the OFT myocardium in regulating cell death and vasculogenesis. The purpose of this study was to determine whether apoptosis in the outflow tract myocardium occurs in the mouse heart during developmental stages comparable to the avian heart and to determine whether differential hypoxia is also present at this site in the murine heart. Apoptosis was detected using a fluorescent vital dye, Lysotracker Red (LTR), in the OFT myocardium of the mouse starting at embryonic day (E) 12.5, peaking at E13.5-14.5, and declining thereafter to low or background levels by E18.5. In addition, high levels of apoptosis were detected in other cardiac regions, including the apices of the ventricles and along the interventricular sulcus. Apoptosis in the myocardium was detected by double-labeling with LTR and cardiomyocyte markers. Terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) and immunostaining for cleaved Caspase-3 were used to confirm the LTR results. At the peak of OFT apoptosis in the mouse, the OFT myocardium was relatively hypoxic, as indicated by specific and intense EF5 staining and HIF1alpha nuclear localization, and was surrounded by the developing vasculature as in the chicken embryo. These findings suggest that cardiomyocyte apoptosis is an evolutionarily conserved mechanism for normal morphogenesis of the outflow tract myocardium in avian and mammalian species.

Animals↗
PubMed1982

Hereditary polymyopathy and cardiomyopathy in the Syrian hamster. II. Development of heart necrotic changes in relation to defective mitochondrial function.

The mitochondrial oxidative phosphorylation, calcium and magnesium contents, and swelling-contraction activity were investigated in relation to the progression of the hereditary hamster cardiomyopathy. The assessment was made in animals between 22 and 232 days of age, which were divided into 7 groups according to stage of disease. In 24-day-old hamsters prior to development of heart necrotic changes, the membrane permeability of isolated mitochondria was altered. In 50-day-old animals, at a stage of disease when myocardial cells undergo degeneration, a defect of oxidative phosphorylation resulting from an increase in mitochondrial calcium was demonstrated. With culmination of the heart necrotic changes, at close to 100 days of age, mitochondrial dysfunction and calcium overload were maximal. There was a transient improvement during the healing stage, but the situation deteriorated with the occurrence of circulatory failure. Since the mitochondrial respiratory pattern and calcium overload parallel the cardiac degeneration, it is inferred that the cell energy depletion is a functional consequence of an abnormal calcium influx.

Animals↗
PubMed1984

Effects of caffeine on the mechanical properties of developing rat heart ventricles.

The effects of caffeine on isometric contractions of right-ventricular strips during the postnatal development of the rat heart were studied. Caffeine (2-10 mM) had a positive inotropic effect on ventricular strips of 3-15-days-old rats but a negative inotropic effect on the muscles of rats older than 22 days. Rest-twitch potentiation was most prominent in the muscles of 3-15-days-old rats but weakened clearly after that age. The potentiation was eliminated by 5 and 10 mM caffeine. An abrupt increase in frequency from 0.2 to 2 Hz caused a positive tension-staircase in 3-15-days-old rats but a negative staircase in older rats, the latter effect being eliminated by caffeine. It is suggested that the observed changes during the third postnatal week are due to a shift from extracellular to intracellular Ca2+ as the main source of this cation.

Action Potentials↗
PubMed1988

Troponin T switching in the developing rat heart.

A monoclonal antibody specific for cardiac troponin T has been used to investigate troponin changes during development in the rat heart. Specificity of the antibody was determined by immunoblot analysis with purified bovine cardiac troponin. In the rat heart, immunoblot analysis shows that anticardiac troponin T reacts with a 42.5-kDa band in fetal ventricles and with a 41-kDa band in adult ventricles. The faster migrating troponin T is present in traces in the fetal heart and increases markedly during the first 2 weeks after birth, concomitantly with the progressive decrease of the slower migrating form that is no longer detectable in the adult. The pattern of reactivity of the monoclonal antibody is not modified by alkaline phosphatase pretreatment, suggesting that the antibody is not specific for a phosphorylated epitope. Conditions known to affect cardiac myosin composition, such as hypothyroidism and hypertrophy secondary to systemic hypertension, do not change the troponin T isoform profile of adult rat ventricles. The expression and accumulation of the adult isoforms of troponin T are not suppressed by propylthiouracil treatment of pregnant and nursing rats.

Aging↗
PubMed2006

High-dose 17beta-estradiol treatment prevents development of heart failure post-myocardial infarction in the rat.

OBJECTIVES: Prognosis of heart failure remains poor despite therapeutic advances, such as angiotensin converting enzyme inhibition or beta-receptor blockade. Thus, more effective forms of treatment are urgently needed. Since estrogens have been shown to modulate migration and proliferation of cardiac fibroblasts and to modulate the expression of estrogen receptors of cardiomyocytes we examined whether high-dose estrogen treatment can affect post-myocardial infarction left ventricular remodeling. METHODS: Female rats were treated with 17beta-estradiol (7.5 mg/90 d) or placebo for ten weeks, starting two weeks prior to experimental myocardial infarction. Eight weeks after infarction, in vivo echocardiographic and hemodynamic measurements as well as isolated heart perfusion were performed. RESULTS: In vivo, chronic estrogen treatment almost completely prevented the development of all signs of heart failure that occur in untreated infarcted hearts, such as increased left ventricular diameters (dilatation), reduced fractional shortening (systolic dysfunction) or increased left ventricular end-diastolic pressure (diastolic dysfunction). In vitro, the right- (indicating structural dilatation) and downward (indicating left ventricular dysfunction) shift of left ventricular pressure-volume curves occurring in untreated infarcted hearts was completely prevented by estrogen. CONCLUSIONS: High dose estradiol treatment prevented development of post-MI remodeling, as assessed by in vivo and in vitro parameters of LV dysfunction. Estrogen may hold the potential of becoming a new form of heart failure treatment.However, the mechanisms responsible for this striking and unexpected beneficial action of estrogen in heart failure remain to be elucidated.

Animals↗
PubMed1992

HNK-1 expression pattern in normal and bis-diamine induced malformed developing rat heart: three dimensional reconstruction analysis using computer graphics.

The spatiotemporal distribution of the immunoreactivity of monoclonal antibody HNK-1 was investigated immunohistochemically in normal and bis-diamine-induced malformed rat embryonic hearts using three-dimensional reconstruction with computer graphics. First recognized in the primitive heart 11.5 days after conception, HNK-1 immunoreactivity was distributed in the atrio-ventricular and bulbo-ventricular junctional areas with incomplete ring-like appearance in the early embryonic stages. In the late embryonic stages the immunoreactive sites were rearranged and localized in the sites topographically corresponding to almost the entire pathway of the conduction system, including the three major internodal tracts connecting the right sinoatrial node and atrioventricular node. Immunoreactivity gradually decreased after the completion of the conduction system, and only a faint reactivity in the atrio-ventricular node region remained in the new-born heart. These results indicate that HNK-1 is expressed temporarily in the pathways corresponding to the conduction system during the development of the heart. In bis-(dichloroacethyl)-octamethylen-diamine (bis-diamine)-induced malformed hearts, localization of HNK-1 immunoreactivity was not remarkably altered in the early embryonic heart. In the late embryo, immunoreactive sites in the sino-atrial node region and atrio-ventricular node region deviated dorsocaudally with the poorly developed internodal tracts, and abnormal distribution was observed in the bilateral atria. We consider that these abnormalities may occur in conjunction with abnormal morphological development such as insufficient absorption of the sinus venosus.

Animals↗
PubMed1987

Identification of two variants of troponin T in the developing chicken heart using a monoclonal antibody.

Troponin T (TNT) expressed in the developing chicken cardiac muscle was examined by immunoblotting combined with two-dimensional electrophoresis (2-D PAGE) and peptide mapping. When the whole lysate of the neonatal heart was examined by 2-D PAGE, two TNT variants were detected on the gel by monoclonal antibody to TNT. Expression of the two variants was developmentally regulated: one isoform (type I) was expressed from embryonic through neonatal stages, and the other (type II) from the late embryonic stage through adulthood during cardiac muscle development. The type-I isoform, but not type-II isoform, was also expressed transiently in chicken skeletal muscle at embryonic stages. As judged from the peptide maps, the two isoforms differed in the N-terminal region but not in the C-terminal region.

Aging↗
PubMed1988

[The development of heart failure during transvalvular catheterization of the left ventricle in spontaneously hypertensive rats].

Systemic hemodynamic parameters in 5-month-old and 10-month-old normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) conscious rats were studied with microsphere technique. Cardiac index was similar in both strains of rats and was not significantly different between 5 and 10 months. Left ventricle catheter implantation through the right common carotid artery evoked the development of heart failure in 10-month-old SHR (in the first day after operation). This model can be used for screening of new drugs for heart failure treatment.

Aging↗
PubMed2003

Diastolic mitral annular velocity during the development of heart failure.

OBJECTIVES: We sought to investigate the mechanism of reduced diastolic mitral annular velocity with diastolic dysfunction, despite elevated left atrial (LA) pressure. BACKGROUND: The peak rate of left ventricular (LV) early diastolic filling (E) and velocity of the mitral annulus due to long-axis lengthening (E(M)) are reduced in mild diastolic dysfunction. With more severe dysfunction, E increases in response to increased LA pressures. In contrast, E(M) decreases, despite increased LA pressure. METHODS: We studied eight dogs instrumented to measure LA pressure, LV pressure, and internal dimensions during the progressive development of heart failure (HF) produced by rapid pacing. RESULTS: Early diastolic filling decreased after four days of pacing from 114 +/- 32 to 88 +/- 22 ml/s (p < 0.05), but with more severe HF, it progressively increased to 155 +/- 32 ml/s (p < 0.05). In contrast, E(M) progressively decreased from 44 +/- 12 mm/s during the control period to 24 +/- 8 mm/s after four weeks (p < 0.05). Although E(M) was related to the time constant of LV relaxation (tau) (R(2) = 0.85), E was not. The latter occurred coincident with termination of the early diastolic LA to LV pressure gradient during all conditions. In contrast, with increasing HF, E(M) was progressively delayed after LA to LV pressure crossover by 37 +/- 12 ms (p < 0.05). The time from E to E(M) was related to tau (R(2) = 0.97). CONCLUSIONS: With slowed relaxation during the development of HF, E(M) is reduced and delayed so that it occurs after early, rapid filling. Thus, with slowed relaxation, E(M) does not respond to the early diastolic LA to LV pressure gradient, because it occurs when LV pressure is greater than or equal to LA pressure.

Animals↗
PubMedDate not supplied

Impairment of mitochondrial and sarcoplasmic reticular functions during the development of heart failure in cardiomyopathic (UM-X7.1) hamsters.

The oxidative phosphorylation as well as calcium transporting properties of heart mitochondria and calcium transport activities of the fragments of the sarcoplasmic reticulum (microsomes) were studied during the life span of cardiomyopathic hamsters (UM-X7.1). Control healthy hamsters of the same age group were used for comparison. No changes in the oxidative phosphorylation ability of cardiomyopathic mitochondria were seen at early and moderate stages of heart failure; however, at severe stages, mitochondrial respiratory functions, but not the ADP:0 ratio, were impaired. Both creatine phosphate and ATP contents were decreased without any significant changes in the ATPase activities of myofibrils from the failing hearts. Heart mitochondria from cardiomyopathic animals at severe stages of failure exhibited less calcium binding and uptake activities in comparison with the control values whereas no changes in the mitochondrial calcium binding and uptake were seen in cardiomyopathic hamsters which showed no clinical signs of heart failure. Although mitochondrial calcium binding in cardiomyopathic hearts at early and moderate stages of failure was decreased, mitochondrial calcium uptake was not significantly different from the control. Microsomal calcium binding activity, unlike calcium uptake activity, was decreased in the hearts of cardiomyopathic hamsters without any signs of heart failure. Both calcium binding and calcium uptake activities of microsomes from animals with early, moderate and severe heart failure were less in comparison with the control values but were not associated with any changes in the Ca2+-stimulated ATPase activity. These results suggest that changes in the process of mitochondrial energy production and mitochondrial Ca2+-transport may be secondary to other factors whereas alterations in the sarcoplasmic reticular Ca2+-transport may lead to the development of heart failure in the cardiomyopathic hamsters.

Adenosine Triphosphatases↗
PubMed2000

The expression of SR calcium transport ATPase and the Na(+)/Ca(2+)Exchanger are antithetically regulated during mouse cardiac development and in Hypo/hyperthyroidism.

The mouse has been used extensively for generating transgenic animal models to study cardiovascular disease. Recently, a number of transgenic mouse models have been created to investigate the importance of sarcoplasmic reticulum (SR) Ca(2+)transport proteins in cardiac pathophysiology. However, the expression and regulation of cardiac SR Ca(2+)ATPase and other Ca(2+)transport proteins have not been studied in detail in the mouse. In this study, we used multiplex RNase mapping analysis to determine SERCA2, phospholamban (PLB), and Na(+)/Ca(2+)-exchanger (NCX-1) gene expression throughout mouse heart development and in hypo/hyperthyroid animals. Our results demonstrate that the expression of SERCA2 and PLB mRNA increase eight-fold from fetal to adult stages, indicating that SR function increases with heart development. In contrast, the expression of the Na(+)/Ca(2+)-exchanger gene is two-fold higher in fetal heart compared to adult. Our study also makes the important observation that in hypothyroidic hearts the NCX-1 mRNA and protein levels were upregulated, whereas the SERCA2 mRNA/protein levels were downregulated. In hyperthyroidic hearts, however, an opposite response was identified. These findings are important and point out that the expression of NCX-1 is regulated antithetically to that of SERCA2 during heart development and in response to alterations in thyroid hormone levels.

Animals↗
PubMed2006

Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction.

The impact of hypertension on left ventricular (LV) structure, pump function, and heart failure in Dahl salt-sensitive rats is poorly characterized but hypothesized to yield insights into the pathophysiology of heart failure with normal or preserved ejection fraction. Eighty Dahl salt-sensitive rats were fed either a high-salt (HS) or low-salt (LS, controls) diet starting at age 7 weeks. Ventricular properties were measured by echocardiography, hemodynamics and end-systolic and end-diastolic pressure-volume relationships (ESPVR and EDPVR, respectively). Compared with LS controls, HS rats developed severe hypertension and LV hypertrophy. At week 12, HS rats developed passive diastolic dysfunction (leftward/upward shifted EDPVR, increased chamber stiffness) with reductions in end-diastolic volume. However, the ESPVR also shifted upward (enhanced end-systolic function) so that overall pump function was enhanced compared with LS, and there was no change in end-diastolic pressure (EDP). At 16 and 20 weeks, HS hearts enlarged so that end-diastolic volumes and EDPVRs became similar to the respective age-matched LS controls. Concomitantly, the ESPVRs and overall pump function curves also moved toward controls, and ejection fraction declined. Despite normal or enhanced overall pump function at these times, EDP and wet lung weight increased, indicative of development of heart failure. In the Dahl salt-sensitive rat, which pathophysiologically retains salt and water, the development of heart failure (increased EDP and wet lung weight) is dissociated from changes in passive diastolic and active systolic properties. These observations suggest that a volume overload sate plays an important pathophysiological role in development of heart failure despite preserved overall ventricular pump function in this model of chronic hypertension.

Animals↗
PubMed1996

Role of endothelium-derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro. Implications for the development of heart failure.

The mechanism responsible for the regulation of cardiac function by endogenous nitric oxide (NO) remains unclear. In this investigation, O2 consumption by freshly isolated myocardial muscle segments from the left ventricular free wall of canine hearts was quantified by a Clark-type O2 electrode at 37 degrees C. S-nitroso-N-acetylpenicillamine (SNAP, 9 +/- 3% to 50 +/- 8%), bradykinin (BK, 14 +/- 3% to 30 +/- 5%), or carbachol (CCh, 15 +/- 4% to 29 +/- 4%) significantly attenuated tissue O2 consumption at doses of 10(-7) to 10(-4) mol/L (mean +/- SE, P < .05). The effects of BK and CCh, but not SNAP, were blocked by 10(-4) mol/L NG-nitro-L-arginine, consistent with both BK and CCh stimulating NO biosynthesis and with SNAP decomposing to release NO, respectively. Similar doses of 8-Br-cGMP caused a respiratory inhibition, but to a lesser extent (9 +/- 2% to 14 +/- 6%). A mitochondrial uncoupler, 2,4-dinitrophenol (at 1 mmol/L), blocked the effects of 8-Br-cGMP, but not those of SNAP, BK, or CCh, suggesting that the major site of action of NO is on mitochondrial electron transport. Myocardial muscle from dogs with pacing-induced heart failure had a basal O2 consumption rate of 251 +/- 21 nmol.min-1.g-1, which was 54% higher than the rate seen in muscle from normal healthy canine hearts. The inhibitory effects of BK and CCh on O2 consumption were not observed in failing cardiac tissue, but SNAP showed an unaltered inhibitory effect. Therefore, our results indicate that NO released from microvascular endothelium by BK, stimulation of muscarinic receptors, and perhaps flow velocity may play an important physiological role in the control of cardiac mitochondrial respiration, and the loss of this regulatory function may contribute to the development of heart failure.

2,4-Dinitrophenol↗
PubMed1994

Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure.

BACKGROUND: Rapid ventricular pacing for 1 day reduced myocardial contractile function without inducing heart failure in conscious, chronically instrumented dogs. After 4 to 7 weeks of pacing, myocardial contractility was depressed further and overt signs of congestive heart failure, eg, ascites, dyspnea, and edema, were evident. METHODS AND RESULTS: The mechanical restitution response, a physiological index of calcium release, was depressed at 1 day of rapid ventricular pacing. Postextrasystolic potentiation was also depressed by a similar amount, 14 +/- 3%, at 1 day after pacing. The response to isoproterenol 0.2 microgram/kg per minute was depressed by a significantly greater amount (P < .05), 52 +/- 7%, at 1 day after pacing. 3H-ryanodine receptor binding fell from 1013 +/- 25 to 808 +/- 42 fmol/mg after 1 day of pacing and remained depressed at similar levels (782 +/- 61 fmol/mg) at 4 to 7 weeks when heart failure was manifest. Ryanodine receptor affinity was unchanged from control values. Neither dihydropyridine binding nor affinity for 3H-PN200-110 was changed from control levels. Within 5 days after recovery from 1 day of pacing, physiological responses to isoproterenol, postextrasystolic potentiation, and mechanical restitution recovered, as did 3H-ryanodine binding density. CONCLUSIONS: These findings suggest that the changes in excitation-contraction coupling and potentially the sarcoplasmic reticulum calcium release channel occur early in the development of heart failure and therefore may be important in the pathogenesis of the contractile abnormalities in this disease state.

Animals↗
PubMed1995

Chronotropic and inotropic effects of histamine in developing chick heart: differential mechanisms before and after hatching.

Chronotropic and inotropic effects of histamine were examined in isolated atrial and ventricular preparations from embryonic and hatched chicken hearts. Histamine produced positive chronotropic and inotropic responses both in embryonic and hatched hearts. The responses to histamine in middle embryonic myocardia, which were observed in the micromolar range, were antagonized by H2 antagonists but not by H1, H3 antagonists and propranolol. Isobutyl-methylxantine, an inhibitor of phosphodiesterase, produced a leftward shift of the concentration-response curve for the chronotropic effect of histamine in the embryo. The responses to histamine in myocardia from hatched chicks, which were observed in the milimolar range, appeared concurrently with the responses to tyramine during development and were antagonized by beta adrenoceptor antagonists but not by any of the histamine antagonists. The positive inotropic response to histamine in hatched ventricular preparations were greatly attenuated by reserpine pretreatment or in the presence of desipramine. Thus, we demonstrated that exogenously applied histamine produces positive chronotropic and inotropic responses in developing chicken hearts and that the mechanisms are different between embryonic and hatched chicks: direct action on H2 receptors in the embryonic heart and release of norepinephrine from sympathetic nerve terminals in hatched hearts.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Fate of the atrioventricular endocardial cushions in the developing chick heart.

To determine the fate of the atrioventricular endocardial cushions in cardiac development, we used staining methods for extracellular fibronectin, which is abundant in the endocardial cushions, and actin, which is abundant in the myocytes. White Leghorn chick embryo hearts were harvested at Hamburger and Hamilton stages 26 to 36, and serial sections of the atrioventricular valve region were stained. Before atrioventricular valve formation, fibronectin and actin staining reveal separation between the fibronectin-rich endocardial cushions and the actin-rich myocardial layer. The developing mitral valve leaflets at all of the observed stages contain a fibronectin-rich matrix but no actin-rich myocytes. In contrast, the tricuspid band includes both fibronectin matrix and actin-rich cells. We conclude that the mitral valve leaflets in the chick form predominantly from the endocardial cushion tissue, and the tricuspid band receives contributions from both the endocardial cushions and surrounding myocardium.

Actins↗
PubMed1996

Sequence of alterations in subcellular organelles during the development of heart dysfunction in diabetes.

Although changes in different subcellular organelles such as myofibrils, sarcoplasmic reticulum (SR), mitochondria and sarcolemma (SL), as well as in heart function have been reported to occur in chronic diabetes, their inter-relationships and functional significance are poorly understood. In order to gain information on this aspect, diabetes in rats was induced by an intravenous injection of streptozotocin and animals were assessed hemodynamically at 15-27 days. Ventricular tissue from several diabetic animals was pooled, subcellular organelles were isolated and their biochemical activities determined. Significant depressions in cardiac contractile and relaxation were observed to be associated with decreases in myofibrillar Ca(2+)-stimulated ATPase and SR Ca(2+)-pump activities at 21 days from the induction of diabetes. Likewise, the SL Na+-Ca2+ exchange and Ca(2+)-channel density were decreased at 21 days but the affinity of SL Ca(2+)-channels was increased in the diabetic heart. The SL Ca(2+)-pump and Na+-K+ ATPase activities were depressed at 18 and 24 days, respectively. Both alpha- and beta- adrenoceptor densities in SL were decreased at 27 days whereas no changes in mitochondrial function were observed at these early stages of diabetes. The SL low affinity Ca(2+)-binding was decreased while the low affinity Ca(2+)-ATPase activity was increased at 18 days following the induction of diabetes. These results indicate that SL defects precede those in SR, myofibrils or mitochondria and suggest that abnormalities in Ca(2+)-handling as well as interaction of Ca2+ with myofilaments in cardiomyocytes may lead to the development of heart dysfunction in chronic diabetes.

Adenosine Triphosphatases↗