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PubMed2005

The role of natriuretic peptides in cardioprotection.

Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating from recent work that ANP and BNP exert their cardioprotective functions not only as circulating hormones but also as local autocrine and/or paracrine factors. In studies using cultured neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP antagonists demonstrated that ANP has antihypertrophic and antifibrotic functions. Corroborating these in vitro results, mice lacking natriuretic receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and fibrosis independent of their blood pressure. Recent studies also suggest that the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role against the intracardiac renin-angiotensin-aldosterone system and TGF-beta mediated pathway. In a clinical setting, human recombinant ANP and BNP may be used for a therapy of heart failure; however, further evaluation is required in the future.

Animals↗
PubMed2005

CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro.

CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated. In this study, we used C2C12 myoblasts and human fetal primary myoblasts to investigate the function of Nkx2.5 in skeletal myogenesis. The expression levels of Nkx2.5 decreased as C2C12 myoblasts elongated and fused to form myotubes. The expression of human NKX2.5 in C2C12 myoblasts inhibited myocyte differentiation and myotube formation, and up-regulated Gata4 and Tbx5 expression. The expression of NKX2.5 in terminally differentiated C2C12 myotubes resulted in a change in morphology and breakdown into smaller myotubes. Furthermore, overexpression of NKX2.5 in C2C12 cells and primary cultures of human fetal myoblasts led to differentiation of myoblasts into neuron-like cells and expression of neuronal markers. This study sheds light on the previously unknown non-cardiac functions of Nkx2.5 transcription factor.

Adenoviridae↗
PubMed1984

The incidence and natural history of pericardial effusion after cardiac surgery--an echocardiographic study.

One hundred twenty-two consecutive patients (104 men; 18 women) were studied to determine the incidence and natural history of pericardial effusion occurring 2, 5, 10, and 20 to 50 days after cardiac surgery. Three patients had pericardial effusions before and 103 patients (91 men; three women) had effusions after surgery. Effusions were first recorded on the second postoperative day in 72 patients, on the fifth postoperative day in 29 patients, and on the tenth postoperative day in two patients. In 96 of these patients, effusions reached their maximum size by postoperative day 10. Of the 103 patients with effusions, 66 (64%) were followed to complete resolution. A specific pattern was observed in most resolving effusions. The echo-free space diagnostic of pericardial effusion became progressively more echo-dense as the effusion diminished in size. As the effusion became echo-dense, the posterior pericardium, which had been motionless, resumed its normal systolic anterior motion. One patient developed cardiac tamponade on postoperative day 3. We conclude that pericardial effusion occurs frequently after cardiac surgery, but that associated complications are rare.

Adult↗
PubMed2003

Deficiency of the vestibular spine in atrioventricular septal defects in human fetuses with down syndrome.

Data on the morphogenesis of atrioventricular septal defect (AVSD) in Down syndrome are lacking to support molecular studies on Down syndrome heart critical region. Therefore, we studied the development of complete AVSD in human embryos and fetuses with trisomy 21 using 3-dimensional graphic reconstructions and immunohistochemical markers. Eight trisomic hearts with AVSD and 10 normal hearts, ranging from 5 to 16 weeks' gestation, were examined. In AVSD, the muscular septum primum and venous valves develop normally, and the size and histology of the nonfused endocardial cushions also appear normal. However, the mass of extracardiac mesenchyme (vestibular spine), located at the dorsal mesocardium, is reduced and does not protrude ventrally along the right wall of the common pulmonary vein. As a result of this, the muscular septum primum and the right pulmonary ridge are seen as 2 separate septa that attach to the inferior endocardial cushion. Both the muscular septum primum and the superiorly fused venous valves (septum spurium) converge and are capped by a small rim of mesenchyme, which forms the roof of the persisting ostium primum and connects to cushions and the reduced vestibular spine. At 7 weeks, ventricular septation in AVSD is comparable to 5 to 6 weeks of normal cardiac development. At later stages, the septum spurium forms the anterosuperior limbus of the septum secundum and the mesenchymal cap becomes the bridging tendon that connects the bridging leaflets. Therefore, reduced expansion of the vestibular spine derived from the dorsal mesocardium appears to play an important role in the development of AVSD in Down syndrome.

Crown-Rump Length↗
PubMed2002

Cardiac-specific expression and hypertrophic upregulation of the feline Na(+)-Ca(2+) exchanger gene H1-promoter in a transgenic mouse model.

The NCX1 gene contains three promoters (H1, K1, and Br1), and as a result of alternative promoter usage and alternative splicing, there are multiple tissue-specific variants of the Na(+)-Ca(2+) exchanger. We have proposed that for NCX1, the H1 promoter regulates expression in the heart, the K1 promoter regulates expression in the kidney, and the Br1 promoter regulates expression in the brain as well as low-level ubiquitous expression. Here, using a transgenic mouse model, we test the role of the DNA region including -1831 to 67 bp of intron 1, encompassing exon H1 of the feline NCX1 gene (NCX1H1). The NCX1H1 promoter was sufficient for driving the normal spatiotemporal pattern of NCX1 expression in cardiac development. The luciferase reporter gene was expressed in a heart-restricted pattern both in early embryos (embryonic days 8 to 14) and in later embryos (after embryonic day 14), when NCX1 is also expressed in other tissues. In the adult, no luciferase activity was detected in the kidney, liver, spleen, uterus, or skeletal muscle; minimal activity was detected in the brain; and very high levels of luciferase expression were detected in the heart. Transverse aortic constriction-operated mice showed significantly increased left ventricular mass after 7 days. In addition, there was a 2-fold upregulation of NCX1H1 promoter activity in the left ventricle in animals after 7 days of pressure overload compared with both control and sham-operated animals. This work demonstrates that the NCX1H1 promoter directs cardiac-specific expression of the exchanger in both the embryo and adult and is also sufficient for the upregulation of NCX1 in response to pressure overload.

Animals↗
PubMed1997

Transgenic mice with cardiac overexpression of alpha1B-adrenergic receptors. In vivo alpha1-adrenergic receptor-mediated regulation of beta-adrenergic signaling.

Transgenic mice were generated with cardiac-specific overexpression of the wild-type (WT) alpha1B-adrenergic receptor (AR) using the murine alpha-myosin heavy chain gene promoter. Previously, we described transgenic mice with alpha-myosin heavy chain-directed expression of a constitutively active mutant alpha1B-AR that had a phenotype of myocardial hypertrophy (Milano, C. A., Dolber, P. C., Rockman, H. A., Bond, R. A., Venable M. E., Allen, L. F., and Lefkowitz, R. J. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10109-10113). In animals with >40-fold WT alpha1-AR overexpression, basal myocardial diacylglycerol content was significantly increased, indicating enhanced alpha1-adrenergic signaling and phospholipase C activity. In contrast to the mice overexpressing constitutively active mutant alpha1B-ARs, the hearts of these mice did not develop cardiac hypertrophy despite an 8-fold increase in ventricular mRNA for atrial natriuretic factor. In vivo physiology was studied in anesthetized intact animals and showed left ventricular contractility in response to the beta-agonist isoproterenol to be significantly depressed in animals overexpressing WT alpha1B-ARs. Membranes purified from the hearts of WT alpha1BAR-overexpressing mice demonstrated significantly attenuated adenylyl cyclase activity basally and after stimulation with isoproterenol, norepinephrine, or phenylephrine. Interestingly, these in vitro changes in signaling were reversed after treating the mice with pertussis toxin, suggesting that the extraordinarily high levels of WT alpha1B-ARs can lead to coupling to pertussis toxin-sensitive G proteins. Another potential contributor to the observed decreased myocardial signaling and function could be enhanced beta-AR desensitization as beta-adrenergic receptor kinase (betaARK1) activity was found to be significantly elevated (>3-fold) in myocardial extracts isolated from WT alpha1B-AR-overexpressing mice. This type of altered signal transduction may become critical in disease conditions such as heart failure where betaARK1 levels are elevated and beta-ARs are down-regulated, leading to a higher percentage of cardiac alpha1-ARs. Thus, these mice serve as a unique experimental model to study the in vivo interactions between alpha- and beta-ARs in the heart.

Adenylate Cyclase Toxin↗
PubMed2002

Association between hypophosphatemia and cardiac arrhythmias in the early stages of sepsis.

BACKGROUND: The purpose of this study was to evaluate a possible association between serum phosphate levels and the incidence of cardiac arrhythmias in the early stages of sepsis. METHODS: We conducted a prospective, controlled study in the General Intensive Care Unit (GICU) of a university hospital. Sixteen patients with sepsis, but without any previous cardiac disease, were studied during their first 24 h in the GICU. Patients were connected to a continuous ECG recording device. Blood samples for serum phosphate level determinations were drawn during the first 6 h after admission to the unit. RESULTS: Ten of 16 patients had 21 episodes of atrial and ventricular arrhythmias. These patients had higher mean Apache II scores (20.2+/-6.2) than the six patients without arrhythmias (13.2+/-1.7; P<0.05) and significantly lower mean phosphate levels (0.73+/-0.16 vs. 1.02+/-0.32 mmol/l; P<0.03). No association was found between serum phosphate levels and mortality among patients with arrhythmias, or when all survivors (with and without arrhythmia) were compared to all non-survivors. CONCLUSIONS: The results indicate that patients with sepsis and low serum phosphate levels are at a greater risk of developing cardiac arrhythmias. We suggest that phosphate supplementation in the early stages of sepsis may prevent cardiac arrhythmias.

Journal Article↗
PubMed2002

KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population.

The long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of the QT interval on electrocardiograms (ECGs), syncope and sudden death caused by a specific ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in ion channel genes including the cardiac sodium channel gene SCN5A, and potassium channel subunit genes KCNQ1, KCNH2, KCNE1, and KCNE2. Little information is available about LQTS mutations in the Chinese population. In this study, we characterized 42 Chinese LQTS families for mutations in the two most common LQTS genes, KCNQ1 and KCNH2. We report here the identification of four novel KCNQ1 mutations and three novel KCNH2 mutations. The KCNQ1 mutations include L191P in the S2-S3 cytoplasmic loop, F275S and S277L in the S5 transmembrane domain, and G306V in the channel pore. The KCNH2 mutations include L413P in transmembrane domain S1, E444D in the extracellular loop between S1 and S2, and L559H in domain S5. The location and character of these mutations expand the spectrum of KCNQ1 and KCNH2 mutations causing LQTS. Excitement, exercises, and stress appear to be the triggers for developing cardiac events (syncope, sudden death) for LQTS patients with KCNQ1 mutations F275S, S277L, and G306V, and all three KCNH2 mutations L413P, E444D and L559H. In contrast, cardiac events for an LQTS patient with KCNQ1 mutation L191P occurred during sleep or awakening from sleep. KCNH2 mutations L413P and L559H are associated with the bifid T waves on ECGs. Inderal or propanolol (a beta blocker) appears to be effective in preventing arrhythmias and syncope for an LQTS patient with the KCNQ1 L191P mutation.

Cation Transport Proteins↗
PubMed2004

N-terminal pro-B-type natriuretic peptide as an indicator of possible cardiovascular disease in severely obese individuals: comparison with patients in different stages of heart failure.

BACKGROUND: Mild stages of heart failure might be difficult to diagnose in severely obese individuals with a body mass index (BMI) >40 kg/m(2). Measurement of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is feasible for detecting cardiac impairment. The aims of our study were to measure NT-proBNP in plasma of severely obese patients and to compare the results with results for patients in different stages of manifest cardiac dysfunction. METHODS: In 61 severely obese individuals (median BMI, 43.2 kg/m(2)) and 96 nonobese patients with existing heart failure [classified into New York Heart Association (NYHA) classes I-IV], NT-proBNP was measured in the fasting condition. A medical history, physical examination, electrocardiography, blood chemistry, and chest x-ray were performed in the obese group. In addition, echocardiography was performed in the NYHA group. RESULTS: In obese individuals, NT-proBNP was increased to a median of 356 (interquartile range, 221-458) pmol/L [854 (530-1099) ng/L] and was comparable (P >0.05) to the median value for NYHA I patients {289 (258-451) pmol/L [694 (619-1082) ng/L]}, but was significantly lower than in the other NYHA groups (P <0.001 for each). CONCLUSION: The prognostic relevance of increased NT-proBNP for risk of developing cardiac insufficiency in severely obese patients needs to be further evaluated.

Adult↗
PubMed1998

tinman-related genes expressed during heart development in Xenopus.

The tinman homeobox gene of Drosophila is absolutely required for development of the insect heart. This observation prompted the isolation of tinman-related genes from vertebrates, in the hope that the developmental function of the gene would be conserved between evolutionarily distinct species. The first vertebrate tinman gene, Nkx2-5, was isolated from mouse and subsequently, orthologues of Nkx2-5 have been isolated from a number of different species. In all cases, a conserved pattern of Nkx2-5 expression is observed in the developing heart, commencing prior to differentiation. Genetic ablation of Nkx2-5 in the mouse results in embryonic lethality due to heart defects, but most myocardial genes are expressed normally and a beating heart tube forms. This observation raises the possibility that additional genes related to Nkx2-5 are partially rescuing Nkx2-5 function in the null mouse. Recently, additional members of the tinman-related gene family have been discovered and characterized in a number of different species. Somewhat surprisingly, orthologous genes in different organisms can be rather divergent in sequence and may show completely different expression patterns. In at least some organisms, expression of the tinman-related genes is not observed in the heart. Due to the increasing number of family members and the somewhat divergent expression patterns, the precise role of the tinman-related genes in cardiac development remains an open question. In a search for additional tinman-related genes in the frog, Xenopus laevis, we have identified Nkx2-9, a novel member of the tinman-related gene family. Preliminary characterization reveals that Nkx2-9 is expressed in the cardiogenic region of the embryo prior to differentiation, but transcript levels decrease rapidly, in the heart, at about the time that differentiation commences.

Animals↗
PubMed1986

Immunoelectron microscopic localization of alpha-actinin and actin in embryonic hamster heart cells.

Myofibrillogenesis in developing cardiac cells of the Syrian hamster from early embryonic stages through newborn was studied by electron microscopy, immunofluorescence microscopy and immunoelectron microscopy. alpha-Actinin and actin were localized at light and electron microscopic levels in embryonic heart cells which had been fixed in a periodate-lysine-paraformaldehyde or a glutaraldehyde-formaldehyde mixture, and embedded in Lowicryl K4M. Indirect staining methods were used for immunofluorescence staining of thick sections and immunoferritin staining of thin sections. The earliest evidence of myofibrillogenesis in embryonic myocardial cells was the presence of many randomly arranged thin (6 nm) filaments and a few scattered thick filaments (15 nm) near the plasma membrane. alpha-Actinin was detected in a semi-continuous, diffuse layer in some portions of the cell just beneath the plasma membrane in association with the filamentous collections. Later in development, alpha-actinin coalesced into Z-plaques at the membrane as the filaments arranged into parallel arrays. Actin was localized in the thin filaments as expected. In later stages of development, alpha-actinin was observed at the Z-lines and intercalated discs of the mature myofibrils while actin was localized at both the I-band and Z-line. Our results suggest that myofibrillogenesis is initiated at the plasma membrane and that Z-plaques are precursors of myofibrillar Z-bands and may serve as organizing centers for myofibrillogenesis in developing cardiomyocytes.

Actinin↗
PubMed2002

Cardiac troponin T variants produced by aberrant splicing of multiple exons in animals with high instances of dilated cardiomyopathy.

Adult cardiac muscle normally expresses a single cardiac troponin T (cTnT). As a potential pathogenic mechanism for turkey dilated cardiomyopathy, the splice-out of a normally constitutive exon generates an additional low molecular weight cTnT with altered conformation and function. We further found that aberrant splicing of cTnT also occurs in several mammals correlating to dilated cardiomyopathy. Skipping of the same exon as that in the turkey was found in the canine cTnT. Splice-out of the adjacent exon 6 occurred in the guinea pig cTnT. Retention of the embryonic exon 5 was found in the cTnT of cat, dog, and guinea pig. These aberrant splicing variants significantly altered the structure of cTnT to sustain functional effects as that in the myopathic turkey cTnT. The genomic sequence of canine cTnT gene shows no specific alterations. However, the alternative splicing patterns of canine cTnT are different in developing cardiac and skeletal muscles, suggesting abnormality of trans-regulatory factors. Transgenic expression of the aberrant cTnT variants resulted in contractile changes in mouse cardiomyocytes. The findings support the hypothesis that thin filament heterogeneity due to the co-expression of alternatively spliced cTnT variants may desynchronize myocardial contraction and contribute to the pathogenesis and pathophysiology of cardiomyopathy and heart failure.

Alternative Splicing↗
PubMed1991

A multivariate analysis of cardiac growth in human embryos: endocardial cushions and ventricular myocardium.

STUDY OBJECTIVE: In view of the controversy about the morphological significance of the endocardial cushion tissue and ventricular myocardium during cardiac development, the aim was to carry out quantitative studies of these structures. DESIGN: Endocardial cushion tissue and ventricular myocardium were quantified by point count planimetry. The relative growth of the volume of these structures, and also the embryonic crown-rump length, was studied by multivariate allometry (principal components analysis) with the covariance matrix calculated from natural logarithms of the data. EXPERIMENTAL MATERIAL: 27 serially sectioned human embryos were studied, ranging from stage 15 to stage 23 (Paris collection). MEASUREMENTS AND MAIN RESULTS: The relative growth of endocardial cushion tissue, ventricular myocardium, and crown-rump length was discontinuous during the postsomitic period. The first component in principal components analysis measures overall size and, in the present analysis, accounts for 88.6% of the total variance. The growth vector isometry hypothesis was checked with the chi 2 test. This showed that differences in growth between cardiac structures and crown-rump length were allometric (p less than 0.01). Endocardial cushion tissue volume and crown-rump length grew with negative allometry during the second month of gestation, while ventricular myocardium volume grew with positive allometry. CONCLUSIONS: The results agree with those researchers who consider that endocardial cushion tissue functions only in causing initial cardiac fusion and partitioning, with little influence on the formation of definitive cardiac structures.

Heart↗
PubMed2000

[Permanent cardiac stimulation in Senegal: preliminary experience at the Cardiology Clinic of Dakar].

We report a prospective and descriptive study in 12 patients who had pacemaker implantation from may. 1996 and dec. 1997. Our patients benefited from complete clinical examination, ECG (12 derivations), standard laboratory tests, chest X ray. Pulsed-Doppler, two dimensional and TM echocardiography have been performed. Stimulation was achieved using endocardial lead introduced percutaneously. During the study, 12 patients over 22, representing 55% of the subjects with symptomatic conduction defects, had definitive pacemaker implantation. Mean age was 53.8 years +/- 18. Most of the patients lived in Dakar. Sex-ratio was 0.58 (7 males/5 females). Most of the patients (83%) had low socio-economical status. Before implantation mean heart rate was 47 bpm +/- 20.8. Mean blood pressure was 155 mmHg +/- 26.7 (systolic) and 71.6 +/- 20.8 mmHg (diastolic). Heart failure was present in 5 patients/12. Others symptoms were mainly syncope (83%). Mean cardiothoracic ratio was 0.56 +/- 0.09. Over a 14 months period we have implanted 7 double chamber stimulators (DDD) and 5 monochamber (VVI). Over a 210 days follow-up, main problems are infection of the pocket in 2 patients. In one of them culture was positive. In Senegal, it is necessary to develop cardiac stimulation. Pacemakers should be available for all patients with symptomatic conduction defects. A national center for electrophysiologic studies and pacemaker implantation is a priority.

Age Distribution↗
PubMed2005

Architecture must document functional evidence to explain the living rhythm.

The central theme of surgical procedures is to interact structure and function. Two reviews of architecture by Torrent-Guasp and Lunkenheimer provide anatomic observations, and then only deduce, rather than test and verify functional relationships. Lunkenheimer previously showed the reciprocal helical configuration of the connective tissue scaffold, a weave-like network that may be the lattice for the descending and ascending segments of Torrent-Guasp's apical loop formed from the helical band. Lunkenheimer stresses cardiac development from a blood vessel, and exposes the need to disregard heart formation by a band that develops between the pulmonary artery and aorta. Torrent-Guasp's band-like concept is confirmed by MRI and sonomicrometer measurements, together with early systolic filling by ongoing, unopposed contraction of the ascending segment of the apical loop. This muscular component contradicts conventional concepts that elastic recoil causes rapid ventricular filling. However, direct physiologic measurements show that Torrrent-Guasp's physiologic timing sequence must be revised. While presumption is an important first step, proof of the marriage of structure and function happens only with measurement, a critical step before surgical action.

Biomechanical Phenomena↗
PubMed1995

Maternal consumption of a low vitamin D diet retards metabolic and contractile development in the neonatal rat heart.

During the fetal and suckling periods of mammalian development, the mother serves as the sole nutritional source for the offspring. As such, the quality of the maternal diet effects growth and development of the offspring during these periods. This study sought to determine if a maternal vitamin D deficiency altered the well characterized development of the neonatal heart. Weaned rat pups (21-day-old) were obtained from mothers who had consumed either a vitamin D-supplemented diet (3000 IU of vitamin D/kg) or a low vitamin D diet (< 200 IU of vitamin D/kg) prior to becoming pregnant and throughout pregnancy and suckling. These pups were sacrificed, hearts excised, and the hearts biochemically analysed for metabolic and contractile protein properties. The pups of dams fed the low vitamin D diet were slightly hypocalcemic relative to those on the supplemented diet (2.28 v 2.41 mumol/l, P < 0.05), had significantly lower body weights (43 v 55 g), heart weights (143 v 174 mg), citrate synthase activity (106 v 147 mumol g-1 min-1), and 3-hydroxyacyl CoA dehydrogenase activity (59 v 91 mumol g-1 min-1). Hexokinase activity (1.98 v 2.02 mumol g-1 min-1), and the distribution of cardiac myosin among its three isoforms (> 85% V1), were unaffected by this dietary deficiency, however myofibrillar protein content was approximately 15% lower in the experimental hearts. These data demonstrate that maternal consumption of a low vitamin D diet results in a general but significant slowing of neonatal cardiac development.

Animals↗
PubMed2001

[Generation of new cardiomyocytes in the adult heart: Prospects of myocardial regeneration as an alternative to cardiac transplantation].

The classic dogma, still prevalent in cardiology, that the adult myocardium is a terminally differentiated tissue unable to produce new cardiomyocytes needs to be revised in light of recent results. In human and experimental animals there is now incontrovertible evidence that new myocytes are continuously generated throughout life in response to physiological and pathological stimuli. Moreover, the elucidation of mechanisms responsible for the hypertrophic response indicate similarity and overlap with the mechanisms involved in cell death by apoptosis as well as cell growth. During cardiac development, from birth to adulthood, there is a balance between the stimuli induce cell growth -by hypertrophy and hyperplasia- on one hand and those that induce programmed cell death on the other. In human and experimental animals it has been well documented that pathological conditions, such as diabetes and hypertension, can increase dramatically the rate of cell death. Moreover, high rates of cell death have been measured in normal adult human hearts and those of mice and rats. No surprisingly, these values increase significantly with age and high in senescence. By themselves, these high rates of normal cell death provide a very compelling argument in favor of cardiomyocyte regeneration. Without cell renewal, these rates of cell death would be incompatible with survival because the heart would disappear before early adulthood. As expected, direct measurement of rates of new cell formation in adult hearts demonstrate high rates of cell renewal that compensate for cell death. Thus, the heart is in continuous cellular turnover with new myocardial cells replacing the older ones. Experiments with fetal mouse cardiocytes shows that the retinoblastoma protein is responsible for the cardiocyte withdrawal from the cell cycle during development. The identification in the adult heart of a subpopulation of quiescent cells that have many of the characteristics of stem cells able to rapidly enter the cell cycle and generate new cardiocytes is yet another evidence that the heart continuously produces new cardiocytes to replace those that disappear either by apoptosis or necrosis.Surprisingly, stem cells other that those from the heart are able to produce new cardiocytes and repopulate the myocardium. We have used bone marrow stem cells injected into the border zone of post-coronary occlusion necrosis. Remarkably, these cells have proven to be very effective in generating new myocardium in the necrotic zone that is integrated to the rest of the muscle and irrigated by new vessels. These results demonstrate that stem cells provide a new avenue for the generation of new contractile tissue. This approach could prove useful in the treatment of chronic cardiac failure and post-ischemic necrosis.

Adult↗
PubMed1994

Elastic extracellular matrix of the embryonic chick heart: an immunohistological study using laser confocal microscopy.

The "elastic matrix" constitutes a specialized component of the extracellular matrix which confers resiliency to tissues and organs subjected to repeated deformations. The role of the elastic matrix in living organisms appears to be of key importance since diseases characterized by expression of defective inherited genes which encode components of the elastic matrix lead to premature death. While the elastic matrix of adult organs has received a great deal of attention, little is known about when it first appears in embryonic tissues or its possible role in developing organs. In the present study we have performed an immunohistochemical study of the distribution of elastin and three additional components often associated with elastic matrices in adult tissues (i.e., fibrillin, emilin, and type VI collagen) during the development of the chicken embryonic heart. The three-dimensional arrangement of these components was established through the observation of whole-amount specimens with scanning laser confocal microscopy. Our results revealed three different periods of heart development regarding the composition of the elastic matrix. Prior to stage 21 the embryonic heart lacks elastin but exhibits a matrix scaffold of fibrillin and emilin associated with the endocardium and the developing cardiac jelly. Between stages 22 and 29 the heart shows a transient elastic scaffold in the outflow tract which contains elastin, fibrillin, and emilin. Elastin-positive fibrillar material is also observed during these stages in the base of the atrioventricular cushion adjacent to the myocardial wall. In addition, emilin-positive material appears to be associated with the zones of formation of ventricular trabeculae. Collagen type VI was not detected during these early stages. From stage 30 to stage 40 a progressive modification of the pattern of distribution of elastin, fibrillin, emilin, and collagen type VI is observed in association with the formation of the definitive four-chambered heart. The distribution of the elastic scaffold in the outflow tract appears to be rearranged and becomes restricted to the roots of the main arteries. Each of the components studied here is also deposited at increasing levels in the developing valvular apparatus including the valve leaflets and the chordae tendinea. The components are also present in the subendocardial space where they form aligned fibrillar tracts, an arrangement suggestive of a role in ventricular contractile function. The epicardium constitutes an additional region of elastic matrix deposition during these later stages and contains elastic, fibrillin, and collagen type VI.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗