Gene expression specific for heart atria and ventricles]

The data on the chamber-specific expression of cardiac genes in the animal and human heart are reviewed. The positional specification of atrial and ventricular gene expression observed in adults is initiated early during embryogenesis. The existence of a cascade of genes is assumed, beginning with genes whose products form an anterior-posterior gradient along the heart-forming regions or along the linear heart tube derived from these regions, and ending with genes that encode the contractile proteins and display chamber-specific expression.     

Basic fibroblast growth factor in atria and ventricles of the vertebrate heart

Extracts from atrial and ventricular heart tissue of several species (chicken, rat, sheep, and cow) are strongly mitogenic for chicken skeletal myoblasts, with the highest apparent concentration of biological activity in the atrial extracts. Using several approaches (biological activity assay and biochemical and immunological analyses), we have established that (a) all cardiac extracts contain an 18,000-D peptide which is identified as basic fibroblast growth factor (bFGF) since it elutes from heparin-Sepharose columns at salt concentrations greater than 1.4 M and is recognized by bFGF-specific affinity-purified antibodies; (b) bFGF is more abundant in the atrial extracts in all species so examined; (c) avian cardiac tissue extracts contain the highest concentration of immunoreactive bFGF; and (d) avian ventricles contain a higher relative molecular mass (23,000-D) bFGF-like peptide which is absent from atrial extracts. Examination of frozen bovine cardiac tissue sections by indirect immunofluorescence using anti-bFGF antibodies shows bFGF-like reactivity associated with nuclei and intercalated discs of muscle fibers. There is substantial accumulation of bFGF around atrial but not ventricular myofibers, resulting most likely from more extensive endomysium in the atria. Blood vessels and single, nonmuscle, connective tissue cells react strongly with the anti- bFGF antibodies. Higher bFGF content and pericellular distribution in atrial muscles suggest a correlation with increased regenerative potential in this tissue. Distribution within the myofibers is intriguing, raising the possibility for an intimate and continuous involvement of bFGF-like components with normal myocardial function.     

Developmental patterns of expression and coexpression of myosin heavy chains in atria and ventricles of the avian heart

Monoclonal antibodies (mAbs), electrophoresis, immunoblotting, and immunohistochemistry were used to determine the molecular properties of cardiac myosin heavy chain (MHC) isoforms and the regions of the developing chicken heart in which they were expressed. Adult atria expressed three electrophoretically distinct MHCs that reacted specifically with mAbs F18, F59, or S58. During embryonic Days 2-4, when the atrial and ventricular chambers are forming, MHCs that reacted with mAbs F18, F59, or S58 were expressed in both the atria and ventricles. The atria continued to express MHCs that reacted with mAbs F18, F59, or S58 at all stages of development and in the adult. In the ventricles, expression of the MHCs reacting with these mAbs was found to be developmentally regulated. By embryonic Day 16, MHC(s) reacting with mAb F18 had disappeared from the developing ventricles, whereas MHCs reacting with S58 and F59 continued to be expressed throughout the ventricles. As development continued, MHC(s) reacting with S58 in the ventricle became restricted to expression in only the ventricular conducting system. MHC(s) reacting with F59 were expressed in both the ventricular myocytes and the ventricular conducting system throughout development and in the adult. Thus, in contrast to the embryonic chicken heart where at least three MHC isoforms were expressed in both the atria and ventricles, we found in the adult chicken heart that-at a minimum-three MHC isoforms were expressed in the atria, two MHC isoforms were expressed in the ventricular conducting system, and one MHC isoform in the ventricular myocardium. MHC isoform expression in the developing avian heart appears to be more complex than previously recognized.     

Action potentials of the heart atria and ventricles of Rana temporaria frogs and Cyprinus carpio carp]

Using microelectrode technique, studies have been made on electrophysiological indices (amplitude of AP, amplitude of the plateau, latent period of AP, duration of maximal depolarization, duration of repolarization at different levels) of cells of isolated atrium and ventricles of the carp during both the spontaneous activity and electrical stimulation. The obtained amplitude-temporal parameters were compared to those of the heart in the frog R. temporaria. It was found that the amplitude of AP, the amplitude of the plateau and the duration of the latent period of AP in both the atrium and ventricles of the carp significantly (p less than 0.01) differ from the corresponding indices of the frog. On the contrary, the duration of maximal depolarization and repolarization in cells from homologous parts of the heart is very close in the species investigated.     

Fluorescence and electron-microscopic analysis of differentiation of the myocytes of the ventricles and atria of the avaian heart in ontogenesis]

The histogenesis of the ventricle and atria myocardium was studied in 240 chick embryos of from 30--34 hours up to 20 days of incubation and in 66 chickens at the age of 1--90 days. Fixators were the Bouin's Carnoy's and Newkomer's fluids and the 100% solution of neutral formalin. The paraffin sections were stained by histological and histochemical methods. RNA, DNA, glycogen and lipids were detected. The ultrafine sections of the material fixed in 1% buffer solution of osmium tetroxide (pH 7,2) and embedded in araldite were prepared for electron microscopy. The contrasting was made in solutions of acetic uranium and lead citrate. Electron microscope--UEMB-100K, accelarating voltage--75 kV. The prefunctional period of cardiogenesis is characterized by most intensive processes of specific differentiation of cardiac myocytes and by accumulation of energetic material. With the growing functional activity of the tubular heart the amount and size of lipid drops in the cytoplasm of differentiating cardiomyocytes diminished suggesting the use of lipids as the main source of energy. In the period of formation of the heart the trabecular myocardium of ventricles and the atria myocardium, seeming to perform the main functional load, are characterized by a better developed contracting apparatus and a considerable content of glycogen granules. A sharp decrease of the glycogen content at the end of the embryonic period is likely to be due to growing hypoxia, the appearance of lung respiration and transition to the other type of energy metabolism.     

A mathematical model of human heart including the effects of heart contractility varying with heart rate changes

Incorporating the intrinsic variability of heart contractility varying with heart rate into the mathematical model of human heart would be useful for addressing the dynamical behaviors of human cardiovascular system, but models with such features were rarely reported. This study focused on the development and evaluation of a mathematical model of the whole heart, including the effects of heart contractility varying with heart rate changes. This model was developed based on a paradigm and model presented by Ottesen and Densielsen, which was used to model ventricular contraction. A piece-wise function together with expressions for time-related parameters were constructed for modeling atrial contraction. Atrial and ventricular parts of the whole heart model were evaluated by comparing with models from literature, and then the whole heart model were assessed through coupling with a simple model of the systemic circulation system and the pulmonary circulation system. The results indicated that both atrial and ventricular parts of the whole heart model could reasonably reflect their contractility varying with heart rate changes, and the whole heart model could exhibit major features of human heart. Results of the parameters variation studies revealed the correlations between the parameters in the whole heart model and performances (including the maximum pressure and the stroke volume) of every chamber. These results would be useful for helping users to adjust parameters in special applications.     

Isolation and characterization of glycosaminoglycans from atria of the human heart

• 1.1. Five glycosaminoglycans were isolated from tryptic digest of atria of the human heart and were assayed by determining the carbohydrate content of materials.
• 2.2. Separation of these 5 polymers was achieved by Dowex 1 × 2 column chromatography.
• 3.3. They were identified as hyaluronic acid, heparan sulfate, chondroitin-4-sulfate, dermatan sulfate and chondroitin-6-sulfate, respectively.

     

Distribution of atrial natriuretic factor in fetal rat atria and ventricles

Summary An immunohistochemical study of rat fetal hearts at 20 days of gestation revealed the presence of immunoreactive atrial natriuretic factor (ANF) in cardiocytes of the left and right atria as well as in certain cells is the left and right ventricles. In the atria, cells of the adluminal pectinate muscles appear more densely labeled than the more peripheral mural cells. In the ventricles, immunoreactive cells were found only in adluminal cardiocytes of the presumptive trabeculae and papillary muscles. The results indicate that ANF is synthesized in the perinatal heart, and that the presence of this hormone in the ventricular cardiocytes may be of only temporary nature during certain stages of pre- and postnatal development.Supported by Miami Valley Chapter of American Heart Association MVH-86-019 and MVH-86-010     

A comparison of myosin light chain subunits in the atria and ventricles of mammals

An SDS-electrophoretic comparison of atrial and ventricular myosin light chain isotypes was performed in mouse, rat, rabbit, dog, pig, rhesus monkey, baboon, human and cow heart. Light chains 1 and 2 in atria and ventricles differed in all species with the possible exception of the rhesus monkey. Relative migration of atrial and ventricular LC-2 isotypes was similar in all species but LC-1 isotypes varied in relative migration rates suggesting increased primary sequence heterogeneity. Order of migration was VLC-1 less than ALC-1 less than ALC-2 less than VLC-2 in mouse, rat, rabbit, dog, baboon and cow and ALC-1 less than VLC-1 less than ALC-2 less than VLC-2 in pig and human heart. No obvious relationship existed between electrophoretic pattern and phylogenetic evolution.     

Immuno-electron microscopy of atrial natriuretic factor secretory pathways in atria and ventricles of control and cardiomyopathic hamsters with heart failure

Summary The secretory pathways of atrial natriuretic factor have been investigated in atrial and ventricular cardiocytes of control and cardiomyopathic Syrian hamsters in severe congestive heart failure with four antibodies: a monoclonal antibody (2H2) against rat synthetic atrial natriuretic factor (101–126), which is directed against region 101–103 of rat atrial natriuretic factor (99–126), and polyclonal, affinity-purified antibodies produced in rabbits against synthetic C-terminal atrial natriuretic factor (101–126), synthetic N-terminal atrial natriuretic factor (11–37) or the putative cleavage site of atrial natriuretic factor (98–99): atrial natriuretic factor (94–103). Application of the immunogold technique on thin frozen sections (immunocryoultramicrotomy) revealed an identical picture with the four antibodies. In atria of both control and cardiomyopathic hamsters where atrial natriuretic factor secretion is regulated, the atrial natriuretic factor propeptide travels, uncleaved, from the Golgi complex to immature and mature secretory granules. In ventricles of control hamsters, where secretion is constitutive, the atrial natriuretic factor propeptide travels from the Golgi complex to secretory vesicles. In the ventricles of hamsters with severe congestive heart failure, the Golgi complex is larger, secretory vesicles more abundant and a few secretory granules are present in 20% of cardiocytes. Here again, the peptide travels uncleaved in all these pathways. These results reveal the pathways of secretion of atrial natriuretic factor in atrial and ventricular cardiocytes and indicate that the propeptide is not cleaved intracellularly.Supported by a grant from the Medical Research Council of Canada to the Multidisciplinary Research Group on Hypertension, by the Canadian Heart Foundation and the Pfizer Company (England)     

Gene expression of the phenylethanolamine N-methyltransferase is differently modulated in cardiac atria and ventricles

Phenylethanolamine N-methyltransferase (PNMT) is a final enzyme in catecholamine synthesizing cascade that converts noradrenaline to adrenaline. Although most profuse in adrenal medulla, PNMT is expressed also in the heart, particularly in cardiac atria and ventricles. In atria, the PNMT mRNA is much more abundant compared to ventricles. In present study we aimed to find out whether there is a difference in modulation of the PNMT gene expression in cardiac atria and ventricles. We used three methodological approaches: cold as a model of mild stress, hypoxia as a model of cardiac ischemic injury, and transgenic rats (TGR) with incorporated mouse renin gene (mREN-2)27, to determine involvement of renin-angiotensin pathway in the PNMT gene expression. We have found that PNMT gene expression was modulated differently in cardiac atria and ventricles. In atria, PNMT mRNA levels were increased by hypoxia, while cold stress decreased PNMT mRNA levels. In ventricles, no significant changes were observed by cold or hypoxia. On the other hand, angiotensin II elevated PNMT gene expression in ventricles, but not in atria. These results suggest that PNMT gene expression is modulated differently in cardiac atria and ventricles and might result in different physiological consequences.     

Thyroid hormones differentially affect sarcoplasmic reticulum function in rat atria and ventricles

The present study was undertaken to compare the effects of hypothyroidism and hyperthyroidism on sarcoplasmic reticulum (SR) Ca²⁺-pump activity, together with assessment of the functional role of SR in providing activator Ca²⁺ under these altered thyroid states. In response to a shift from hypothyroid to hyperthyroid state, a 10 fold and 2 fold increase in SR Ca²⁺-pump activity in atria and ventricles, respectively, were observed. This was associated with the 8-9 fold increases in atrial contractility (+dT/dt) and relaxation (-dT/dt), but only with a 3-4 fold increase in their ventricular counterparts. Also, the recirculation fraction of activator Ca²⁺ (RFA) increased to a far greater extent in atria (4 fold) than in papillary muscles, and the relative increment in inhibition of developed tension by ryanodine became 3 times larger in atria than in papillary muscles. A positive force-frequency relationship (FFR) was observed in hypothyroid atria, whereas the hyperthyroid atria, hypothyroid and hyperthyroid papillary muscles showed a negative FFR. These results suggest the greater role of transsarcolemmal (SL) Ca²⁺ and smaller role of SR Ca²⁺ in activating contraction in hypothyroid atria compared to other preparations. Thyroid hormones decrease the contribution of SL and increase that of SR in providing activator Ca²⁺ to the greater extent in atria than in ventricles. This effect of thyroid hormones is based on larger stimulation of SR Ca²⁺-pump in atria compared to ventricles.     

Development of different electrophysiological mechanisms for muscarinic inhibition of atria and ventricles

The negative inotropic effect of acetylcholine (ACh) in atrial muscle can be accounted for by a decrease of a voltage- and time-dependent slow inward current (Isi) carried by Ca2+/Na+ and an increase of outward time-dependent current carried by K+ (IK1) through inwardly rectifying channels. The negative inotropic effect of ACh in ventricular muscle is associated with a reduction of Isi; there is no important effect of ACh on IK1 in ventricular muscle. Because atrial and ventricular muscles display IK1 that is sensitive to Ba2+ and have similar numbers of muscarinic receptor sites, it is concluded that ventricular muscle lacks a metabolic link between the muscarinic receptor and inwardly rectifying K+ channels. Although there is much evidence for cyclic nucleotides as the mediator between muscarinic receptors and Isi channels, cyclic nucleotides do not seem to connect these receptors with inwardly rectifying K+ channels. According to this hypothesis, identification of a metabolic link between muscarinic receptors and IK1 channels should be demonstrable in atrial but not ventricular muscle.     

Comparative effects of dihydropyridine inhibitors of calcium penetration on spontaneous contraction of the isolated heart atria in the guinea pig

All DHPs (nifedipine, nicardipine, nitrendipine) produced a concentration-dependent depression of the isometric contraction and of the atrial rate of the isolated, spontaneously beating atria of the guinea-pig. The depressive actions of nifedipine and nitrendipine were completely antagonized by the addition of calcium, aminophylline and isoprenaline. Aminophylline partially, calcium almost completely and isoprenaline completely antagonized the depressive action of nicardipine on the isometric contraction. Only isoprenaline antagonized the effect of DHPs on the atrial rate of the isolated, spontaneously beating atria of the guinea-pig. It is possible that all these substances restore the contractibility of the atria by compensating the calcium balance, previously changed by DHPs, or by producing an increase in the intracellular cyclic AMP content (aminophylline and isoprenaline).     

A model of heart ventricles for electrocardiographic evaluation of the state of the myocardium

A mathematical model of heart excitation processes has been developed for describing an electrocardiogram. A verified archive of model electrocardiograms has been created with the use of the model. The model has been used to study how electrocardiograms are affected by individual variability in ventricle shape and heart position in the norm, in myocardial infarction of different localizations, and in ventricular hypertrophy. Correspondence of the specific features of real and model electrocardiograms is discussed.     

Modelling of the heart and pericardium at end-diastole

Herein we present a refined version of Vito's two-sphere static model of the heart with pericardium and discuss its possible applications. The improvements we make on Vito's model are: (i) Vito assumed that the elastic materials which constitute the model 'heart' and 'pericardium' are isotropic; we relax this assumption to that of transverse-isotropy. (ii) Our analysis, which does not assume the existence of stored-energy functions, links the model directly to empirical stress-strain relations of suitable biaxial uniform-extension tests; two such stress-strain relations (one for the pericardium, one for the myocardium, both of which may be described by the same equation except for difference in the values of response parameters) now define the model completely, so we avoid altogether the difficult task of determining full-fledged constitutive equations for the pericardium and myocardium. As for applications, we contend that the concentric spheres in static equilibrium can be taken as a model of the left ventricle and pericardium at end-diastole. We show that the model when equipped with suitable stress-strain relations does give good fit to the pressure-volume data which Spotnitz et al. (1966, Circulation Res., 18, 49-66) obtained from excised canine left ventricles and to the pericardium data which Pegram et al. (1975, Circulation Res., 9, 707-714) obtained from closed chest, anaesthetized dogs. Three different empirical formulae were tried in the data-fitting as the equation that describes the requisite stress-strain relations. The 'exponential law' gave the best results.