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PubMed2003

Effect of hypo- and hyperthyroid states on phospholipid composition in developing rat heart.

The aim of this study was to examine the effect of hypo- and hyperthyroidism on the phospholipid composition in developing rat heart. The hypothyroid state (PTU) was induced by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from the postnatal day 2-21. The hyperthyroidism (T3) was made by daily injection of 3,3',5-triiodo-L-thyronine (10 microg/100 g body wt) to newborns in the same time period. Age matched intact littermates were taken as euthyroid controls. PTU decreased the concentration of total phospholipids (PL), choline phosphoglycerides (PC), ethanolamine phosphoglycerides (PE) and diphosphatidylglycerol (DPG) and increased the proportion of plasmalogen component of PE (PLPE). T3 increased the concentration of PL, PC, PE, DPG and decreased PLPE in comparison with euthyroid controls. The ratio of saturated/unsaturated fatty acids (FA) in PE was decreased in PTU and increased in T3 group. The ratio of n-6/n-3 polyunsaturated FA in PC, PE and phosphatidylinositol (PI) was increased in PTU due to increase of 18:2n-6 and decrease of 22:6n-3 proportion. T3 decreased this ratio because of decline in 20:4n-6 and rise in 22:6n-3 proportion. Both hypo- and hyperthyroidism decreased the ratio of 20:4n-6/18:2n-6 in the majority of phospholipids. PTU decreased the unsaturation index in PC, PI and phosphatidylserine. It is concluded that thyroid state plays an essential role in the development of membrane phospholipid components in cardiac membranes during the early postnatal period.

Animals↗
PubMedDate not supplied

Efficacy of captopril in relieving congestive heart failure developing during management of hypertension. Case report.

A 20-year-old woman presented with malignant hypertension, pulmonary edema, anemia, and azotemia. Blood pressure was adequately controlled only after progressively more intensive drug regimens, finally including minoxidil, nadolol, and furosemide. On these drugs, the patient developed progressive left and right heart failure, anasarca, and malnutrition. The control of hypertension, heart failure, and fluid retention, was accomplished by administration of captopril and furosemide. Captopril is a logical alternative to vasodilators in refractory hypertension complicated by congestive heart failure.

Adult↗
PubMed2002

Spatiotemporal and tissue specific distribution of apoptosis in the developing chick heart.

To investigate spatial and temporal distributions of apoptosis in the embryonic chick heart and its relation to different tissue types, we examined apoptosis in the embryonic chick heart from Hamburger and Hamilton stage 17 through 3 days after hatching. MF20 antibody, alpha-smooth muscle actin (SMA) antibody and EAP-300 antibody were applied to delineate specific cell types. During early development of the embryonic chick heart, very few apoptotic cells were detected. The first distinctive zone of apoptosis was observed in the outflow tract at stage 25. This focus was most prominent during septation of the pulmonary artery from the aorta (i.e., between stages 28 and 29), and diminished to virtually background level by stage 32, except in the subconal regions. Subsequently, remarkable apoptosis appeared in the atrioventricular cushions by stage 26, peaked at stages 29-31, and dropped significantly thereafter. Characteristic distribution patterns of apoptotic cells were also detected in the cardiac conduction tissues, including the His bundle, the bundle branches, and the ventricular trabeculae. After stage 36, cell death dropped to background level, except in developing coronary vessels. MF20 and TUNEL double staining revealed that apoptosis in cardiomyocytes was limited to a few specific regions, much less than in cushion tissues. SMA and TUNEL double staining demonstrated that vascular structures were the major foci of apoptosis from stage 40 to 44, whereas adjacent perivascular Purkinje cells displayed significantly less cell death at these stages. The characteristic spatiotemporal locations of apoptosis parallel the morphologic changes and tissue differentiation during heart development, suggesting that apoptosis is crucial to the transformation of the heart from a simple tube to a complex multichambered pump.

Actins↗
PubMed2004

Heart valve development: endothelial cell signaling and differentiation.

During the past decade, single gene disruption in mice and large-scale mutagenesis screens in zebrafish have elucidated many fundamental genetic pathways that govern early heart patterning and differentiation. Specifically, a number of genes have been revealed serendipitously to play important and selective roles in cardiac valve development. These initially surprising results have now converged on a finite number of signaling pathways that regulate endothelial proliferation and differentiation in developing and postnatal heart valves. This review highlights the roles of the most well-established ligands and signaling pathways, including VEGF, NFATc1, Notch, Wnt/beta-catenin, BMP/TGF-beta, ErbB, and NF1/Ras. Based on the interactions among and relative timing of these pathways, a signaling network model for heart valve development is proposed.

Animals↗
PubMed2005

Inflammation, as measured by the erythrocyte sedimentation rate, is an independent predictor for the development of heart failure.

OBJECTIVES: Our objective was to explore inflammation, measured as erythrocyte sedimentation rate (ESR), as a predictor for the development of heart failure (HF). BACKGROUND: In recent years, evidence of the importance of inflammation in the pathophysiology of HF has emerged, and various inflammatory markers have been found to predict future HF. Erythrocyte sedimentation rate is an inexpensive and easily accessible marker of systemic inflammation, but to this date it is unknown whether ESR predicts subsequent HF. METHODS: In a community-based prospective study of 2,314 middle-aged men free from HF, myocardial infarction, and valvular disease at baseline, ESR was analyzed in multivariable models together with established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) and hematocrit. RESULTS: A total of 282 men developed HF during a median follow-up time of 30 years. In Cox proportional hazards analyses, ESR was an independent predictor of HF (hazard ratio 1.46 for highest quartile vs. the lowest, 95% confidence interval 1.04 to 2.06). This observation remained significant when also adjusting for interim myocardial infarction during follow-up. CONCLUSIONS: Erythrocyte sedimentation rate was a significant predictor of HF, independent of established risk factors for HF, and interim myocardial infarction after three decades of follow-up in a population-based sample of middle-aged men. Our findings indicate that inflammation occurs early in the process leading to HF and that ESR could be used to evaluate this process.

Blood Sedimentation↗
PubMed1998

Dynamic left/right regionalisation of endogenous myosin light chain 3F transcripts in the developing mouse heart.

It has recently emerged that transcriptional differences exist between left and right cardiac chambers. An example is provided by transgenic mice with an nlacZ reporter gene under transcriptional control of the fast skeletal muscle alkali myosin light chain (MLC) 3 promoter and 3' enhancer, which express beta-galactosidase in a left ventricular-right atrial dominant pattern in the developing and adult heart. Here, we demonstrate that endogenous MLC3F transcripts are also left/right regionalised in the mouse heart during embryonic development. Regionalisation is observed as early as embryonic day (E) 8.5, and by E10.5 MLC3F transcripts are present predominantly in the future left ventricle and right atrium, and to a lesser extent in the left atrium. Subsequently, MLC3F transcripts are down-regulated in the left ventricle, and by E12.5 expression is restricted to both atria and left-ventricular trabeculae. No MLC3F protein can be detected in the adult or embryonic mouse heart, suggesting that post-transcriptional regulation prevents this fast myosin isoform contributing to myocardial contraction. Left ventricular-right atrial dominant MLC3F transgenes therefore reflect transitory left/right regionalisation of the endogenous gene, unlike other reported cases of transgene regionalisation. MLC3F transgenes, however, maintain an embryonic-like distribution throughout development suggesting that myocardial gene expression is controlled by distinct temporal, as well as spatial, regulatory modules.

Age Factors↗
PubMed2004

Lethal outcomes in patients with symptomatic heart failure developed after Q-wave myocardial infarction.

The article analyses clinical characteristics and mortality of patients with symptomatic chronic heart failure following Q-wave myocardial infarction. During the study 224 patients (mean age 64.1+/-9.7) with symptomatic chronic heart failure and left ventricular ejection fraction <40% were followed-up for 1-5 years (on the average, 2.6+/-2.0 years). The majority of the studied patients had had anterior or anterior-lower Q-wave myocardial infarction (61.6% and 25.9%, respectively) and an identified Canadian function class II-IV angina pectoris (74.6%), and one-fifth of the patients (19.6%) had unstable angina pectoris. All patients were diagnosed with chronic heart failure New York Heart Association function class II-IV, the majority of patients had disturbances in cardiac rhythm and conduction, almost a half of them (46.0%) had left ventricular aneurysm, 92.8% of patients were diagnosed with marked changes in left ventricular geometry, 84.4% of patients had II-IV degrees mitral regurgitation, a half of the patients had significant left ventricular diastolic dysfunction, and 6.3% of patients had previously experienced thromboembolic complications. During the follow-up period 132 patients died. The comparison of the characteristics of patients who survived with those of patients who died showed that the deceased patients were statistically significantly older compared to survivors; in addition to that, marked stenoses of three coronary arteries, severe chronic heart failure, ejection fraction < or =20%, ventricular extrasystoles, and sinal tachycardia were more common in the former group, and patients who died less frequently were overweight and less frequently used beta adrenoblockers. The evaluation of Kaplan-Meier curves showed that total mortality resulting from the development of chronic heart failure symptoms and indications of chronic heart failure during the 1st year was 21.0%, during the 2nd year -40%, during the 3rd year -55.0%, during the 4th year -61.0%, and during the 5th year -65.0% the highest mortality was observed when left ventricular ejection fraction < or =20%, and age >75. The development of severe chronic heart failure resulted, on the average, after 1.5+/-1.1 years. It is obvious that symptomatic chronic heart failure caused by ischemic cardiomyopathy and marked left ventricular systolic dysfunction following Q-wave myocardial infarction is a rapidly progressing process conditioning high risk of lethal outcome within the period of several years.

Adult↗
PubMed1984

Metabolic and contractile function enhancement during rat heart postnatal development.

Enhanced cardiac contractile function during the early post-birth period is a mammalian characteristic; however, concurrent metabolic measurements have not been systematically carried out. To define heart postnatal development, left ventricular pressure and rate of left ventricular pressure development (dP/dt) were measured in rats at 3, 5, 7, and 9 weeks post birth. When functional measurements were completed, the heart was excised, weighed, and tissue samples were used for chemical and/or enzymatic analyses. Left ventricular weight increased approximately 5-fold over the period studied, but was outstripped by 8-fold increases in body weight. Left ventricular DNA content increased dramatically between 3 weeks and 7 weeks post birth, then stabilized between 7 and 9 weeks post birth. Minor fluctuations in phosphofructokinase and lactate dehydrogenase enzyme activities suggest that glycolytic and anaerobic metabolisms undergo relatively small alterations as normal growth and development transpire. In contrast, enzymatic indices of aerobic metabolism (citrate synthase and malate dehydrogenase) were augmented approximately 6-fold without significant change in specific enzyme activity in purified mitochondria. Thus, mitochondria accumulated more rapidly than left ventricular tissue during heart growth. Magnesium-stimulated, myofibrillar ATPase enzyme activity approximately doubled over the intervening time between 3 weeks and 9 weeks post birth. Heart contractile function is augmented during normal growth roughly in parallel with increases in cell numbers, mitochondrial mass, and myofibrillar ATPase activity.

Adenosine Triphosphatases↗
PubMed2002

The heart LIM protein gene (Hlp), expressed in the developing and adult heart, defines a new tissue-specific LIM-only protein family.

In a subtraction designed to identify transcripts accompanying mesodermal lineage specification in mouse ES differentiation cultures, we identified a gene encoding a two LIM-domain protein which we named heart LIM protein (Hlp). Hlp is most closely related to thymus LIM protein, and these two genes comprise a new gene family related to the cysteine-rich protein (CRP) gene family. In the embryo, Hlp expression is primarily restricted to the developing heart. In situ hybridization showed expression at E7.75 in the paired heart-forming primordia prior to linear heart-tube formation. At E8.5, strong expression is detected in the heart, with equal expression in both heart chambers. Hlp expression is detected in both myocardium and endocardium, and in vascular endothelium. Later in fetal development low levels of Hlp expression are detected outside the heart, including dorsal root ganglia and the spinal cord. In the adult, Hlp is expressed at highest levels in the heart, and at lower levels in the brain, skeletal muscle and aorta. Hlp expression is unchanged in hypertrophic hearts induced by aortic constriction. These data suggest a role for the two LIM-domain gene Hlp in the very earliest stages of heart differentiation and development.

Amino Acid Sequence↗
PubMed2006

Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4.

The function of the p53 tumor suppressor to inhibit proliferation or initiate apoptosis is often abrogated in tumor cells. Mdm2 and its homolog, Mdm4, are critical inhibitors of p53 that are often overexpressed in human tumors. In mice, loss of Mdm2 or Mdm4 leads to embryonic lethal phenotypes that are completely rescued by concomitant loss of p53. To examine the role of Mdm2 and Mdm4 in a temporal and tissue-specific manner and to determine the relationships of these inhibitors to each other, we generated conditional alleles. We deleted Mdm2 and Mdm4 in cardiomyocytes, since proliferation and apoptosis are important processes in heart development. Mice lacking Mdm2 in the heart were embryonic lethal and showed defects at the time recombination occurred. A critical number of cardiomyocytes were lost by embryonic day 13.5, resulting in heart failure. This phenotype was completely rescued by deletion of p53. Mice lacking Mdm4 in the heart were born at the correct ratio and appeared to be normal. Our studies provide the first direct evidence that Mdm2 can function in the absence of Mdm4 to regulate p53 activity in a tissue-specific manner. Moreover, Mdm4 cannot compensate for the loss of Mdm2 in heart development.

Alleles↗
PubMed1997

Temporal and spatial asymmetries in the initial distribution of mesenchyme cells in the atrioventricular canal cushions of the developing chick heart.

BACKGROUND: We investigated potential early asymmetries in the distribution of mesenchymal cells within the inferior and superior AV cushions in the developing chick heart. METHODS: Chick embryos stages 16-20 HH were fixed, embedded in polyacrylamide, and the cell nuclei stained with propidium iodide. Cells counts were determined within the cardiac jelly of the atrioventricular canal (AV) by laser confocal microscopy in coronal planes spanning its entire length. RESULTS: Our data show at the different stages studied, 16-20 HH, that the inferior AV cushion invariably contains more cells than the superior AV cushion. In the inferior cushion, the cell distribution is bimodal, i.e., the proximal and distal regions have more mesenchymal cells than the middle part of the AV canal. In the superior cushion, there is a increasing gradient of mesenchymal cells along the longitudinal axis from the atrium to the ventricle. CONCLUSIONS: Our findings reveal that the temporal and spatial characteristics of mesenchyme formation in the inferior vs. superior AV cushion are different. This asymmetry suggests several potential hypotheses: (1) the distribution of the inducer molecule or its receptor has a distribution similar to that of mesenchymal cells, (2) the extracellular matrix has a differential composition or regionally-specific physical associations, (3) the endocardium is heterogeneous with respect to transformation capacity, or (4) these patterns result from an earlier inductive event. The potential importance of the observed asymmetries in the distribution of AV mesenchyme is discussed relative to localization patterns of molecules critical to successful cardiac morphogenesis and remodeling.

Animals↗
PubMed2000

Vasoactive intestinal polypeptide and calcitonin gene-related peptide in the developing rat heart atria.

Vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) and calcitonin gene-related peptide (CGRP)-LI concentrations were determined in the developing rat heart atria using radioimmunoassay. Peptide levels were analysed on postnatal days 1, 10, 25, 45, 60, and 85 (P1-P85) separately in the right (RA) and left atria (LA). No sex differences were revealed at any age examined. VIP-LI has been already detected in both atria at P1 in concentrations comparable to values at P10. In the RA, VIP-LI levels increased significantly between days P10 and P25, remained high at P45 and then declined. In the LA, VIP-LI concentrations did not differ from those in the RA on days P1, P10, P25, and P45. However, regional differences were found at P60 and P85, when the peptide levels were significantly higher in the LA than in the RA. The postnatal changes in CGRP-LI concentrations were comparable in both atria with similar values at P1 and P85. After birth, CGRP levels decreased gradually till P45, then they increased till P60 and declined again at P85. The results demonstrate that there is an asymmetry in the postnatal development of the atrial VIP-LI and CGRP-LI concentrations. VIP-LI levels reached their maximum at P25, whereas CGRP-LI levels at P60. Relatively high peptide concentrations in neonatal atria and their variations during development might be related to diverse trophic functions of VIP and CGRP.

Animals↗
PubMed1996

Development of heart rate power spectra reveals neonatal peculiarities of cardiorespiratory control.

Postnatal adaptation should be associated with changes in cardiac rhythmic behavior. To examine the development of heart rate variability, instantaneous heart rate (IHR) and the corresponding breathing signals of 16 healthy infants were analyzed. This was pursued by use of fast Fourier transformation beginning with the 1st day until the 6th mo of life. Power in the low-frequency range (LF, 0.02-0.2 Hz) and high-frequency range (HF, 0.2-1.5 Hz), total power (TP), the quotient LF/HF, and the frequency of the peak in LF and HF (LFF and HFF, respectively) were derived from the IHR spectrum. The peak frequency in HF (RF) was detected in the respiratory spectrum. Power and frequency of IHR rhythms undergo a marked development. TP, LF, and HF are lowest from the end of the 1st mo until the 2nd mo. LF predominates over HF, with LF/HF reaching its peak during 1- to 2-mo period. HF, recording respiratory related rhythms is negatively correlated with the breathing rate (BR). HFF and RF both show an increasing tendency during the 1st mo followed by a decrease down to the 6th mo. However, HFF is lower than RF if BR is high, mainly during the first 2 mo. The distinct changes in BR and its important influence on the IHR spectrum underscore the importance of monitoring respiration as a further measure in the diagnosis of infants. LFF is on average between 0.075 and 0.095 Hz, exhibiting an irregular course with minimum at the 10th, 21st-28th, and 90th day being apparent. The developmental pattern of LFF may by interpreted in terms of the maturation of the nervous system involved in the generation of circulatory rhythms.

Aging↗
PubMed2006

Bmp2 and Gata4 function additively to rescue heart tube development in the absence of retinoids.

We used the vitamin A-deficient (VAD) quail model to investigate the retinoid-dependent mechanism that regulates heart tube development. We showed previously that decreased levels of Gata4 in cardiogenic mesoderm and endoderm correlate with the cardiomyopathy caused by VAD, but that this could be rescued by transplanting normal anterior endoderm. Bmp2 is a known cardiogenic factor that is expressed normally in lateral plate mesoderm and cardiac-associated pharyngeal endoderm. Here we show that (like Gata4) transcripts encoding Bmp2 and BMP-dependent signaling activity are decreased throughout the heart-forming region of the VAD embryo. Addition of Bmp2 protein or forced expression of Gata4 in cultured VAD embryos leads to a partial rescue of the cardiomyopathy, and addition of both Bmp2 and Gata4 has an additive positive effect. Our data are consistent with a requirement for retinoid signaling to maintain expression of Bmp2, which regulates Gata4, and in addition acts with Gata4 to regulate genes important for normal morphogenesis of the primitive heart tube.

Animals↗
PubMed2000

Molecular cloning of junctin from human and developing rabbit heart.

Canine junctin is a 26-kDa transmembrane protein found in the sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscle. Junctin has recently been shown to bind directly to calsequestrin, the ryanodine receptor, and triadin. Junctin is thought to play a role in facilitating (and perhaps regulating) Ca(2+) release from the SR. Immature heart exhibits decreased utilization of SR Ca(2+) stores for cell contraction. We have cloned human and rabbit cardiac junctin and investigated the expression of junctin in developing rabbit heart. Human junctin was cloned from an adult cardiac cDNA library. Rabbit junctin was cloned by RT-PCR. Northern blot analysis demonstrates a single primary mRNA transcript of approximately 2.8 kb in hearts from both species. Sequence analysis demonstrates greater than 97% homology between the predicted amino acid sequences of human, rabbit, and canine junctin in the putative transmembrane domain and subsequent initial 61 amino acid portion of the putative luminal domain. These domains also exhibit sequence homology with triadin. The C-terminal region shows much lower (72 to 75%) sequence homology among the three species. In addition, Northern blot analysis demonstrates that the expression of junctin increases markedly in postnatal rabbit myocardium. These findings suggest that the putative transmembrane domain and subsequent initial portion of the putative luminal domain of junctin play an important role in the binding of junctin to calsequestrin, the ryanodine receptor, and triadin in the postnatal heart. Furthermore, the previously described increase in SR Ca(2+) release with development is associated with the increased expression of junctin.

Adult↗
PubMed1987

The role of active myocarditis in the development of heart failure in chronic Chagas' disease: a study based on endomyocardial biopsies.

The authors analyze the presence of active myocarditis in endomyocardial biopsies from 38 patients with chronic Chagas' disease diagnosed serologically. The patients were divided into three clinical groups of increasing severity. Group I: 13 patients with normal electrocardiograms, normal chest x-rays, and no symptoms; Group II: 13 patients with abnormal electrocardiograms and no cardiomegaly; and Group III: 12 patients with abnormal electrocardiograms, cardiomegaly and heart failure. In order to diagnose myocarditis activity, two sets of criteria were used: one mainly observing histopathologic aspects of inflammatory cells aggressing cardiac fibers; and the other counting the mean number of lymphocytes per high power microscopic field. The results of both methods showed a higher incidence of active myocarditis in the clinical group with heart failure. The present report clearly shows the important role played by activity of myocarditis in the development of heart failure in chronic Chagas' disease. Therefore, the possibility of using drugs to control early stages of the activity of the inflammatory process is suggested. On the other hand, endomyocardial biopsy (EMB) seems to be an adequate method to evaluate the intensity of the cardiac inflammatory process in Chagas' heart disease.

Adolescent↗
PubMed2000

Vital epidemiologic clues in heart failure.

The epidemiologic investigation of heart failure evolution by the Framingham Heart Study has provided vital clues concerning the pathogenesis, predisposing conditions, other predictive risk factors, and indicators of deteriorating ventricular function related to the disease. This information is important in the early detection of those susceptible to heart failure who are candidates for preventive measures-of importance because the prevalence of the disease has not declined despite the recent therapeutic advances. Epidemiologic investigation has identified useful indicators for the disease including a low or falling vital capacity suggesting diastolic dysfunction, a rapid resting heart rate in compensation for a decreased stroke volume, and cardiomegaly indicating myocardial hypertrophy or dilatation. Hypertension and coronary disease remain the leading causes of the disease, and heart failure due to myocardial infarction has increased in prevalence. Hypertension and coronary disease often coexist in individuals who develop heart failure so that correction and prevention of these conditions deserve a high priority. Early detection and correction of insulin resistance is important because a threefold increase in the prevalence of diabetes in the general population has serious implications for the incidence of heart failure. In patients with hypertension, the occurrence of a myocardial infarction increases the risk of developing heart failure five to sixfold, whereas angina increases it less than twofold. In these patients, the presence of left ventricular hypertrophy increases the risk of developing heart failure two- to threefold. Heart failure-related mortality remains unacceptably high, despite improvements in treatment, indicating a need for early detection and treatment of predisposing conditions.

Aged↗
PubMed1997

Development of heart inter-beat interval variability in preweanling rats: effects of exposure to alcohol and hypoxia.

The effect of alcohol exposure and hypoxia on the development of heart rate and heart inter-beat interval (IBI) variability was studied in preweanling rats. Rats were artificially reared from postnatal day (PD) 4 through 12 and either exposed to alcohol (5 g/kg/day) or hypoxia (2-15-min episodes/day) from PD 4 to 10. Control groups consisted of artificially reared and normally reared rats not exposed to alcohol or hypoxia. The heart rate and respiration was recorded for 20-min sessions every other day from PD 5 through 21. Inter-beat intervals and measures of their variability caused by respiratory sinus arrhythmia (RSA) were computed from the recordings. There was a steady decline in average IBI across this age range. There was little change in RSA from PD 5 to 15, followed by a large increase in RSA level from PD 15 to 21. The alcohol- and hypoxia-exposed rats showed significantly less increase in RSA level on PD 19 and 21. Large bradycardias occurred in all groups on PD 5, 9, and 17, and were more prevalent in rats exposed to alcohol or hypoxia. These data suggest that neural control of the chronotropic functions of the heart undergoes major changes in the late preweanling stage, and the changes in neural control are slowed by hypoxia or alcohol exposure during the early postnatal period.

Animals↗