The formation of the right and left heart ventricles from the ventricular part of the cardiac tube during embryogenesis

It has been generally assumed that the initial rudiment of the heart ventricle is divided by the longitudinal interventricular septum into the right and left ventricles. This paper presents evidence for the hypothesis that the right and the left ventricles are produced during normal development from different sequentially located segments of the cardiac tube. These segments yielding rudiments of the right and left ventricles could be detected even during early embryogenesis. This hypothesis requires a new explanation for the process of the formation of two separate outlets from the heart ventricles.     

Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles.

The locations, projections, and functions of the intracardiac ganglia are incompletely understood. Immunocytochemical labeling with the general neuronal marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution of intracardiac neurons throughout the cat atria and ventricles. Fluorescence microscopy was used to determine the number of neurons within these ganglia. There are eight regions of the cat heart that contain intracardiac ganglia. The numbers of neurons found within these intracardiac ganglia vary dramatically. The total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly divided between the atria and the ventricles. The largest ganglion is found in the interventricular septum (IVS). Retrogradely labeled fluorescent tracer studies indicated that the vagal intracardiac innervation of the anterior surface of the right ventricle originates predominantly in the IVS ganglion. A cranioventricular (CV) ganglion was retrogradely labeled from the anterior surface of the left ventricle but not from the anterior surface of the right ventricle. These new neuroanatomic data support the prior physiological hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on the left ventricle. A total of three separate intracardiac ganglia innervate the left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion. However, the IVS ganglion provides the major source of innervation to both the left and right ventricles. This dual innervation pattern may help to coordinate or segregate vagal effects on left and right ventricular performance.     

Effect of hypoxia on pig heart short-chain acylcarnitines

The right ventricles of pig heart were perfused with hypoxic blood and the left ventricles were perfused with normally ventilated arterial blood. Free carnitine and short-chain acylcarnitines in hypoxic ventricles were lower than in perfused controls, and much lower than in non-perfused heart. Acetylcarnitine levels decreased and the branched-chain acylcarnitines and propionylcarnitine were elevated in the hypoxic perfused ventricles. These data indicate that both hypoxia and anaesthesia caused loss of carnitine and short-chain acylcarnitines from the heart and hypoxia also changed the distribution of short-chain acylcarnitines in the heart.     

Myocyte ploidy in heart chambers of birds with different locomotor activity

The ploidy levels of atrio- and ventriculocytes were determined by means of cytofluorimetry in 31 species of birds. The obtained data were collated with postnatal growth rate, heart mass index, and relative masses of heart chambers. The difference between mean ploidy of cardiomyocytes in the left and right atrium is small (7.9+/-0.6%) and comparable to the difference in the masses of these chambers (10.5+/-0.8%). The difference between mean ploidy of atrio- and ventriculocytes is most pronounced for the left and right parts of heart (23.9+/-1.4% and 24.0+/-1.3%, respectively) and corresponds to considerable differences in the average masses of atria and ventricles (4.5-fold and 2.1-fold, respectively). The mean cardiomyocyte ploidy levels in the left and right ventricles differ only slightly, as in the case of atria (by 8.1+/-0.5%), whereas the average mass of the left ventricle is greater by 237+/-16%. This discord can be explained by peculiarities of the growth, which is nonproportionally faster in the left ventricle during the last stage of proliferative heart growth as compared to other chambers. The cardiomyocyte ploidy is higher in birds with a relatively small heart and lower ability to flight. Birds with a high locomotor activity in the adult state have an athletic heart (mass index >1%); they are fast growing, altricial species with a low heart workload in the early postnatal ontogenesis. Birds with a low locomotor activity at the adult state are precocial; they grow slowly and have a high locomotor activity from the first minutes of life. Thus, notwithstanding the fact that a greater elevation of cardiomyocyte ploidy level is acquired under a higher functional load (ventricles vs. atria, left vs. right part of the heart), it is associated with a lower functional potential of the organ at the adult state. The level of somatic polyploidy can be considered an indicator of developmental tensions arising due to a high workload during the growth of a given organ and deficiency of resources invested into this growth. J. Exp. Zool. 293:427-441, 2002.     

The quantitative relationship between longitudinal and radial function in left, right, and total heart pumping in humans

The total heart volume variation (THVV) during systole has been proposed to be caused by radial function of the ventricles, but definitive data for both ventricles have not been presented. Furthermore, the right ventricle (RV) has been suggested to have a greater longitudinal pumping component than the left ventricle (LV). Therefore, we aimed to compare the stroke volume (SV) generated by radial function to the volume variation of the left, right, and total heart. To do this, we also needed to develop a new method for measuring the contribution of the longitudinal atrioventricular plane displacement (AVPD) to the RVSV (RVSV(AVPD)). For our study, 11 volunteers underwent cine MRI in the short- and long-axis planes and MRI flow measurement in all vessels leading to and from the heart. The left, right, and total heart showed correlations between volume variation from flow measurements and radial function calculated as SV minus the longitudinal function (r = 0.81, P < 0.01; r = 0.80, P < 0.01; and r = 0.92, P < 0.001, respectively). Compared with the LV, the RV had a greater AVPD (23.4 +/- 0.8 vs. 16.4 +/- 0.5 mm), center of volume movement (13.0 +/- 0.7 vs. 7.8 +/- 0.4 mm), and, RVSV(AVPD) (82 +/- 2% vs. 60 +/- 2%) (P < 0.001 for all). We found that THVV is predominantly caused by radial function of the ventricles. Longitudinal AVPD accounts for approximately 80% of the RVSV, compared with approximately 60% for the LVSV. This difference explains the larger portion of THVV found on the left side of the heart.     

Effect of ectopic excitation on pump function of the hen and dog right heart ventricle

The pump function of the right heart ventricle has been studied in anesthetized dogs and hens at sinus rhythm, supraventricular rhythm, and subepicardial ectopic excitation of base and apex of the right and left ventricles. Dynamics of the ventricle intracavital pressure was recorded by transmural catheterization. In hens, the pump function of the right ventricle (as compared with sinus rhythm) was preserved to the greater degree at stimulation of the left ventricle apex and deteriorated significantly at stimulation of the right ventricle, whereas in dogs, it retained to the greater degree (as compared with supraventricular rhythm) at stimulation of the left ventricle base and deteriorated at stimulation of the right ventricle apex. Changes of the pump function of the right heart ventricle at ectopic ventricle stimulation are similar in birds and mammals. Differences in changes of dog and hen pump functions under effect of location of the ectopic excitation seem to be due to morphofunctional peculiarities of heart ventricles.     

Nature of the relation between contractile activity indices of the left and right heart ventricles in normal and pathological conditions

Positive correlations were established between contractile activity of left and right rabbit ventricles in normal conditions, reflecting synchronous activity of both heart ventricles. These correlations could be broken in case of pathology due to disturbances of adaptation mechanisms resulting in the impairment of heart functioning.     

Topography of lymphatic collectors and regional lymph nodes of the canine heart and their morphological characteristics

In 40 dogs lymphatic vessels and regional lymph nodes of the heart have been prepared. Morphology of the regional lymph nodes have been studied by means of various histological techniques. Lymph outflow from the canine ventricles is realized by three (less often), or by two (more often) collectors. In very rare cases one collector is formed. From the right atrium lymph flows out in two collectors (cranial and left). Lymphatic vessels of the left atrium get into the left collector of the ventricles, or into the tracheobronchial lymph nodes. Into the same nodes gets the lymphatic vessel, forming at the border of the left and right atrii. Cranial, medial, caudal mediastinal nodes (lymphatic mediastinal system) and right, middle and left tracheobronchial lymph nodes (tracheobronchial system) are regional lymph nodes of the canine heart. In the lymph nodes of the tracheobronchial system of puppies older than one month presence of exogenic pigment and signs of fibrous degeneration of parenchyma are noted.     

Changes in the activity of some metabolic enzymes in the heart of SHR rat incurred by transgenic expression of CD36

Hypertension, dyslipidemia, and insulin resistance in the spontaneously hypertensive rat (SHR) can be alleviated by rescuing CD36 fatty acid translocase. The present study investigated whether transgenic rescue of CD36 in SHR could affect mitochondrial function and activity of selected metabolic enzymes in the heart. These analyses were conducted on ventricular preparations derived from SHR and from transgenic strain SHR-Cd36 that expresses a functional wild-type CD36. Our respirometric measurements revealed that mitochondria isolated from the left ventricles exhibited two times higher respiratory activity than those isolated from the right ventricles. Whereas, we did not observe any significant changes in functioning of the mitochondrial respiratory system between both rat strains, enzyme activities of total hexokinase, and both mitochondrial and total malate dehydrogenase were markedly decreased in the left ventricles of transgenic rats, compared to SHR. We also detected downregulated expression of the succinate dehydrogenase subunit SdhB (complex II) and 70 kDa peroxisomal membrane protein in the left ventricles of SHR-Cd36. These data indicate that CD36 may affect in a unique fashion metabolic substrate flexibility of the left and right ventricles.     

Vascularization of the conducting system in the human heart

On 200 randomized specimens of the human heart, of either sex, from 20 to 80 years of age, we investigated the vascularization of the conducting system of the heart in relation to the type of coronary ramification, by the dissection, injection-corrosive, radiographic and coronarographic method. The symmetrical type of arterial vascularization was established in 24%, the right type in 63% and the left type in 13% of the cases investigated. The sinoatrial node is vascularized in 60% by the right and in 40% of the cases by the left coronary artery. The atrioventricular node and the stem of the atrioventricular bundle are vascularized by the right coronary artery in 85% of the cases investigated, in 13% by the left and in 2% by both arteries. The right fasciculus of the atrioventricular bundle is vascularized by the left artery, the left fasciculus by both arteries. The vascularization of the posterior strand in both ventricles is conformable to the type of arterial vascularization of the heart.     

Serotonin-mediated protein carbonylation in the right heart

Pulmonary hypertension is a devastating disease, which leads to right heart failure. Serotonin (5-HT) plays important roles in the pathogenesis of pulmonary hypertension and pulmonary vascular remodeling. The role of 5-HT in right heart failure, however, is unknown. Since oxidative stress may mediate heart failure, the present study examined the effects of 5-HT on protein oxidation in the adult rat right heart ventricle. Treatment of perfused isolated hearts with 5-HT resulted in the promotion of protein carbonylation, specifically in the right ventricle, but not in the left. While no differences between right and left ventricular antioxidant enzymes and 5-HT receptors/transporter were detected, monoamine oxidase A (MAO-A) expression and activity were found to be lower in the right ventricle compared to the left. These results indicate that differences in neither the reactive oxygen species (ROS) scavenging ability, 5-HT membrane signaling capacity, nor MAO-dependent production of hydrogen peroxide are responsible for varied 5-HT-mediated protein carbonylation in right and left ventricles. Rather, lower MAO-A in the right heart might preserve cytosolic 5-HT which triggers other mechanisms for ROS production. Consistently, inhibition of MAO-A resulted in the promotion of protein carbonylation. We propose that low MAO-A, thus reduced degradation of 5-HT, increases the intracellular 5-HT activity in the right ventricle, leading to the promotion of protein carbonylation.     

Effect of ectopic excitation on the ventricular pump function in chicken

The pump function of the heart ventricles was studied in chest-open anaesthetized adult female chickens under sinus rhythm and ectopic excitation of different localization. The intraventricular pressure in the right and left heart ventricles was measured by insertion of catheters through the ventricular free walls. Maximum systolic pressure, end-diastolic pressure, contractility (dP/dtmax) and relaxation (dP/dtmin) of both heart ventricles, and duration of the asynchronous contraction time of the left ventricle were analyzed. It was revealed that reduction of the pump function of the left ventricle tends to be greater under right ventricular ectopic excitation compared with left ventricular one. In comparison with the sinus rhythm, the pump function of the right ventricle was preserved to a greater extent under stimulation of the left ventricular apex and was significantly impaired under right ventricular ectopic excitation. Relaxation of both heart ventricles was more susceptible to ventricular ectopic excitation than contractility, and was more vulnerable in the right ventricle than in the left one. The direction of changes of the pump function of the heart ventricles in chickens under ventricular ectopic excitation was similar to changes of the pump function of mammalian hearts.     

Atrial natriuretic factor messenger ribonucleic acid and peptide in the human heart during ontogenic development

We have investigated the level of expression of the atrial natriuretic factor (ANF) gene in the human heart during ontogenic development by determining the concentrations of ANF messenger ribonucleic acid (ANF mRNA), of immunoreactive ANF (IR ANF) and of receptor reactive ANF (RR ANF), in myocardial samples of the various heart chambers. We found the level was high and almost identical in the left and right ventricles in utero. It gradually decreased during ontogenic development to reach the low adult levels, with a more rapid decrease in the right than in the left ventricle after birth. In the atria, ANF gene expression was high as early as the 13th week of gestation, was higher in the right than in the left atrium, and appeared little affected by ontogenic development.     

Histamine and the heart

Histamine has been known as a cardiac stimulant for over 70 years. Work in our laboratory over the past decade has established that histamine receptors exist in the hearts of various species. The type of histamine receptor varies not only between species but also in the various regions of the heart. In the guinea pig heart H1 receptors are found in left atria and ventricles while H2 receptors are found in right atria and are the predominant histamine receptor in the ventricles. Rabbit atria contain both H1 and H2 receptors while the ventricles appear to possess only H1. Rat and cat heart do not seem to have histamine receptors and the positive inotropic and chronotropic effects elicited by histamine in cardiac preparations of these species are due to the release of noradrenaline. Dog heart contains H1 receptors while human heart has H2 receptors. In all cases H2 receptors are associated with adenylate cyclase and stimulation of such receptors results in an increase in cyclic AMP levels. H1 receptors are not associated with cyclic nucleotides in the heart. There are certain similarities between beta-adrenergic and H2-histaminergic receptors as well as between alpha-adrenergic and H1-histaminergic receptors. Stimulation of either histamine receptor must result in an increase in the free calcium ion concentration in the cardiac cell but the mechanisms involved are obviously different.     

Subcellular Ca2+ transport in different areas of dog heart

Calcium transport and ATPase activities were determined in the heavy and mitochondrial fractions isolated from the left and right atria as well as ventricles of dogs. Ultrastructural distribution of these organelles in different areas of the myocardium was also examined. Calcium binding, calcium uptake, and calcium ATPase activities of the atrial microsomes were lower than those of the ventricles. On the other hand, mitochondrial calcium binding and uptake activities in the right atrium were higher than those in other areas. The mitochondrial total ATPase activities in the atria were also higher than those in the ventricles. Mitochondrial as well as microsomal yields from ventricles were significantly higher. Size and number of mitochondria in the ventricles were greater whereas no striking difference in the distribution of sarcoplasmic reticulum was apparent in different areas of the heart. Poorly developed calcium transport functions in the atrial microsomes may be one of the factors responsible for the generation of lower contractile force in this tissue in comparison with the ventricle.     

Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart

Molecular mechanisms for the dorso-ventral patterning and interventricular septum formation in the embryonic heart are unknown. To investigate a role of Hand1/eHAND in cardiac chamber formation, we generated Hand1/eHAND knock-in mice where Hand1/eHAND cDNA was placed under the control of the MLC2V promoter. In Hand1/eHAND knock-in mice, the outer curvature of the right and left ventricles expanded more markedly. Moreover, there was no interventricular groove or septum formation, although molecularly, Hand1/eHAND knock-in hearts had two ventricles. However, the morphology of the inner curvature of the ventricles, the atrioventricular canal, and the outflow tract was not affected by Hand1/eHAND expression. Furthermore, expression of Hand1/eHAND in the whole ventricles altered the expression patterns of Chisel, ANF, and Hand2/dHAND but did not affect Tbx5 expression. In contrast, the interventricular septum formed normally in transgenic embryos overexpressing Hand1/eHAND in the right ventricle but not in the boundary region. These results suggested that Hand1/eHAND is involved in expansion of the ventricular walls and that absence of Hand1/eHAND expression in the boundary region between the right and left ventricles may be critical in the proper formation of the interventricular groove and septum. Furthermore, Hand1/eHAND is not a master regulatory gene that specifies the left ventricle myocyte lineage but may control the dorso-ventral patterning in concert with additional genes.     

Myocyte cytoskeletal disorganization and right heart failure in hypoxia-induced neonatal pulmonary hypertension

Previous studies have demonstrated that environmentally or genetically induced changes in the intracellular proteins that compose the cytoskeleton can contribute to heart failure. Because neonatal right ventricular myocytes are immature and are in the process of significant cytoskeletal change, we hypothesized that they may be particularly susceptible to pressure stress. Newborn calves exposed to hypobaric hypoxia (barometric pressure = 430 mmHg) for 14 days developed severe pulmonary hypertension (pulmonary arterial pressure = 101 +/- 6 vs. 27 +/- 1 mmHg) and right heart failure compared with age-matched controls. Light microscopy showed partial loss of myocardial striations in the failing neonatal right but not left ventricles and in neither ventricle of adolescent cattle dying of altitude-induced right heart failure. In neonatal calves, immunohistochemical analysis of the cytoskeletal proteins (vinculin, metavinculin, desmin, vimentin, and cadherin) showed selectively, within the failing right ventricles, patchy areas characterized by loss and disorganization of costameres and intercalated discs. Within myocytes from the failing ventricles, vinculin and desmin were observed to redistribute diffusely within the cytosol, metavinculin appeared in disorganized clumps, and vimentin immunoreactivity was markedly decreased. Western blot analysis of the failing right ventricular myocardium showed, compared with control, vinculin and desmin to be little changed in total content but redistributed from insoluble (structural) to soluble (cytosolic) fractions; metavinculin total content was markedly decreased, tubulin content increased, particularly in the structural fraction, and cadherin total content and distribution were unchanged. We conclude that hypoxic pulmonary hypertensive-induced neonatal right ventricular failure is associated with disorganization of the cytoskeletal architecture.     

Effects of streptozotocin-induced diabetes on action potentials in the sinoatrial node compared with other regions of the rat heart

In vivo biotelemetry studies have demonstrated that heart rate (HR) is progressively and rapidly reduced after administration of streptozotocin (STZ) and that the reduction in HR can be partially normalized with insulin replacement. Reductions in HR have also been reported in isolated perfused heart and superfused right atrial preparations suggesting that intrinsic defects in the heart are at least partly responsible for the bradycardia. The regional effects of STZ-induced diabetes mellitus (DM) on action potentials (APs) in the sinoatrial node (SAN), right and left atria and ventricles have been compared in the spontaneously beating Langendorff perfused rat heart 10–12 weeks after treatment. HR was significantly reduced in STZ-induced diabetic rat heart (174 ± 9 BPM) compared to controls (241 ± 12 BPM). The duration of AP repolarization at 50% and 70% from peak AP was significantly prolonged in SAN, right atrium and right ventricle from STZ-induced diabetic rat compared to age-matched controls. In the SAN AP duration (APD) at 50% and 70% were 51.7 ± 2.2 and 59.5 ± 2.3 ms in diabetic rat heart compared to 45.2 ± 1.7 and 50.0 ± 1.6 ms in controls, respectively. In contrast APD at 50% and 70% were not significantly altered in the left atrium and left ventricle. Regional defects in the expression and/or electrophysiology of SAN ion channels, and in particular those involved in AP repolarization, might underlie heart rhythm disturbances in the STZ-induced DM rat.