The formation of the right and left heart ventricles from the ventricular portion of the heart tube in 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 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.     

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.     

Human cardiac myosin heavy chain isoforms in fetal and failing adult atria and ventricles

The goal of this study was to test the hypothesis that the relative amounts of the cardiac myosin heavy chain (MHC) isoforms MHC-alpha and MHC-beta change during development and transition to heart failure in the human myocardium. The relative amounts of MHC-alpha and MHC-beta in ventricular and atrial samples from fetal (gestational days 47--110) and nonfailing and failing adult hearts were determined. The majority of the fetal right and left ventricular samples contained small relative amounts of MHC-alpha (mean < 5% of total MHC). There was a small significant decrease in the level of MHC-alpha in the ventricles between 7 and 12 wk of gestation. Fetal atria expressed predominantly MHC-alpha (mean > 95%), with MHC-beta being detected in most samples. The majority of adult nonfailing right and left ventricular samples had detectable levels of MHC-alpha ranging from 1 to 10%. Failing right and left ventricles expressed a significantly lower level of MHC-alpha. MHC-alpha comprised approximately 90% of the total MHC in adult nonfailing left atria, whereas the relative amount of MHC-alpha in the left atria of individuals with dilated or ischemic cardiomyopathy was approximately 50%. The differences in MHC isoform composition between fetal and nonfailing adult atria and between fetal and nonfailing adult ventricles were not statistically significant. We concluded that the MHC isoform compositions of fetal human atria are the same as those of nonfailing adult atria and that the ventricular MHC isoform composition is different between adult nonfailing and failing hearts. Furthermore, the marked alteration in atrial MHC isoform composition, associated with cardiomyopathy, does not represent a regression to a pattern that is uniquely characteristic of the fetal stage.     

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.     

Simulation of the cardiovascular system using equivalent electronic system

This paper describes simulation of the cardiovascular system using a complex electronic circuit. In this study we have taken a slightly different approach to the modeling of the system and tried to advance existing electrical models by increasing more segments and parameters. The model consists of 42 segments representing the arterial system. Anatomical and physiological data for circuit parameters have been extracted from medical articles and textbooks. The frequency of heart is 1 Hz and the system operates in steady state condition. Each artery is modeled by one capacitor, resistor and inductor. The left and right ventricles are modeled using AC power suppliers and diodes. The results of the simulation including pressure and volume graphs exhibit operation of the cardiovascular system under normal condition. The results of the simulation have been compared with the relevant experimental observation and are in good agreement with them.     

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 hypoxic hypoxia on taurine concentrations in ventricles of mouse hearts

The effects of hypoxic hypoxia on the concentration of taurine in right ventricles was studied in the hearts of male CF1 mice caged individually and maintained for 16 hr per day in a hypobaric chamber evacuated to an air pressure of 307 mm Hg. After 23 days hearts were excised and right and left ventricles were separated and lyophilized. Hematocrits in chamber animals were 77-82%, compared to 45-49% for control mice. Mean weights of right ventricles of animals from the chamber were 11.2 +/- 0.9, compared to control values of 7.0 +/- 0.4, mg dry weight. The mean dry weights of left ventricles in both groups of animals were the same. There were no significant differences in the nmoles taurine per mg day tissue in either heart chamber, with mean values +/- S.E.M. of 124.0 +/- 4.6 and 135.0 +/- 4.5 in right ventricles and 128.0 +/- 4.3 and 110.9 +/- 15.3 in left ventricles of experimental and control animals respectively. Thus, hypertrophy which results from hypoxia is not accompanied by increased concentrations of taurine in right ventricles.     

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.     

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.     

The effect of disease on human cardiac protein expression profiles in paired samples from right and left ventricles

Background

Cardiac diseases (e.g. coronary and valve) are associated with ventricular cellular remodeling. However, ventricular biopsies from left and right ventricles from patients with different pathologies are rare and thus little is known about disease-induced cellular remodeling in both sides of the heart and between different diseases. We hypothesized that the protein expression profiles between right and left ventricles of patients with aortic valve stenosis (AVS) and patients with coronary artery disease (CAD) are different and that the protein profile is different between the two diseases. Left and right ventricular biopsies were collected from patients with either CAD or AVS. The biopsies were processed for proteomic analysis using isobaric tandem mass tagging and analyzed by reverse phase nano-LC-MS/MS. Western blot for selected proteins showed strong correlation with proteomic analysis.

Results

Proteomic analysis between ventricles of the same disease (intra-disease) and between ventricles of different diseases (inter-disease) identified more than 500 proteins detected in all relevant ventricular biopsies. Comparison between ventricles and disease state was focused on proteins with relatively high fold (±1.2 fold difference) and significant (P < 0.05) differences. Intra-disease protein expression differences between left and right ventricles were largely structural for AVS patients and largely signaling/metabolism for CAD. Proteins commonly associated with hypertrophy were also different in the AVS group but with lower fold difference. Inter-disease differences between left ventricles of AVS and CAD were detected in 9 proteins. However, inter-disease differences between the right ventricles of CAD and AVS patients were associated with differences in 73 proteins. The majority of proteins which had a significant difference in one ventricle compared to the other pathology also had a similar trend in the adjacent ventricle.

Conclusions

This work demonstrates for the first time that left and right ventricles have a different proteome and that the difference is dependent on the type of disease. Inter-disease differential expression was more prominent for right ventricles. The finding that a protein change in one ventricle was often associated with a similar trend in the adjacent ventricle for a large number of proteins suggests cross-talk proteome remodeling between adjacent ventricles.     

Effects of glossopharyngeal insufflation on cardiac function: an echocardiographic study in elite breath-hold divers.

Glossopharyngeal insufflation (GI), a technique used by breath-hold divers to increase lung volume and augment diving depth and duration, is associated with untoward hemodynamic consequences. To study the cardiac effects of GI, we performed transthoracic echocardiography, using the subcostal window, in five elite breath-hold divers at rest and during GI. During GI, heart rate increased in all divers (mean of 53 beats/min to a mean of 100 beats/min), and blood pressure fell dramatically (mean systolic, 112 to 52 mmHg; mean diastolic, 75 mmHg to nondetectable). GI induced a 46% decrease in mean left ventricular end-diastolic area, 70% decrease in left ventricular end-diastolic volume, 49% increase in mean right ventricular end-diastolic area, and 160% increase in mean right ventricular end-diastolic volume. GI also induced biventricular systolic dysfunction; left ventricular ejection fraction decreased from 0.60 to a mean of 0.30 (P = 0.012); right ventricular ejection fraction, from 0.75 to a mean of 0.39 (P < 0.001). Wall motion of both ventricles became significantly abnormal during GI; the most prominent left ventricular abnormalities involved hypokinesis or dyskinesis of the interventricular septum, while right ventricular wall motion abnormalities involved all visible segments. In two divers, the inferior vena cava dilated with the appearance of spontaneous contrast during GI, signaling increased right atrial pressure and central venous stasis. Hypotension during GI is associated with acute biventricular systolic dysfunction. The echocardiographic pattern of right ventricular systolic dysfunction is consistent with acute pressure overload, whereas concurrent left ventricular systolic dysfunction is likely due to ventricular interdependence.     

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.     

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.     

Non-linear dynamic analysis of the cardiac rhythm during transient myocardial ischemia.

Coronary artery occlusions related to myocardial ischemia drive cardiac control system reactions that may lead to heart failure. The purpose of this study was to assess the autonomic nervous system (ANS) response during prolonged percutaneous transluminal coronary angioplasty (PTCA). Continuous ECG data were acquired from 50 patients before and during PTCA, with occlusions in the left anterior descending, left circumflex or right coronary artery. Heart rate variability (HRV) was analyzed for 3-min segments of the R-R interval signal obtained from ECG data. The ANS behavior was evaluated by HRV analysis using fractal-like indices. The fractal scalar exponent alpha(1) and power-law slope beta decreased considerably during PTCA. This indicates that significant reactions of autonomic control of the heart rate occurred during coronary artery occlusions, with a reduction in complexity of the ANS.     

Cardiac myosin phenotype remodeling following chronic spinal transection

Spinal transection results in profound neural and functional changes of the heart. However, phenotypic alterations in cardiac myosin heavy chains (MyHC) as a result of spinal transection have not been explored. Hearts were removed from 180 day old rats who had their spinal cords transected between T6 and T9 (ST; n = 10) and intact controls (IN; n = 9). Myosin was isolated from the left and right ventricles and separated into its respective heavy chain components (designated as alpha and beta) by SDS-PAGE. The resulting gels were scanned with a laser scanning densitometer to obtain relative concentrations of these two heavy chains. The left ventricles of the ST rats had a significantly higher (p < 0.05) alpha to beta ratio (10.89) than the intact controls (4.20), while the right ventricle of the ST rats had a significantly lower (p < 0.05) alpha to beta ratio (7.49) relative to intact controls (13.62). The left and right ventricular weight to body weight ratios were not different in ST compared to IN. Additionally, there were significant within group differences (p < 0.05) between the alpha and beta MyHC ratios for the left and right ventricles. These data suggest that 1) spinal transection causes remodeling of the right and left ventricles and 2) the two ventricles do not remodel as a unit.     

Pressure overload and neurohumoral activation differentially affect the myocardial proteome

Treatment with monocrotaline causes pulmonary hypertension in rats. This results in severe pressure overload-induced hypertrophy of the right ventricles, whilst the normally loaded left ventricles do not hypertrophy. Both ventricles are affected by enhanced neuroendocrine stimulation in this model. We analyzed in this model load-induced and catecholamine-induced changes of right and left ventricular proteome by two-dimensional gel electrophoresis, tryptic in-gel digest, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. All analyzed animals showed right ventricular hypertrophy without signs of heart failure. Changes of 27 proteins in the right and 21 proteins in the left ventricular myocardium were found. Given the hemodynamic features of this animal model, proteome changes restricted to the right ventricle are caused by pressure overload. We describe for the first time a potentially novel pathway (BRAP2/BRCA1) that is involved in myocardial hypertrophy. Furthermore, we demonstrate that increased afterload-induced hypertrophy leads to striking changes in the energy metabolism with down-regulation of pyruvate dehydrogenase (subunit beta E1), isocitrate dehydrogenase, succinyl coenzyme A ligase, NADH dehydrogenase, ubiquinol-cytochrome C reductase, and propionyl coenzyme A carboxylase. These changes go in parallel with alterations of the thin filament proteome (troponin T, tropomyosin), probably associated with Ca(2+) sensitization of the myofilaments. In contrast, neurohumoral stimulation of the left ventricle increases the abundance of proteins relevant for energy metabolism. This study represents the first in-depth analysis of global proteome alterations in a controlled animal model of pressure overload-induced myocardial hypertrophy.