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.     

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.     

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 intermittent high altitude hypoxia on the structure and enzymatic activity of cardiac myosin

The time course of structural and enzymatic changes in cardiac myosin was studied in the right and left ventricle of rats exposed to intermittent high altitude (IHA) hypoxia. In the controls, ATPase activity and myosin structure in both ventricles was the same. After the third exposure to simulated high altitude (2 600 m), myosin enzymatic activity rose significantly in the left ventricle and a significant right-left difference appeared. In the next phase of adaptation (11 exposures, 6 000 m), myosin ATPase activity fell in both ventricles and the right-left difference disappeared. After the 16th exposure (7 000 m), enzymatic activity increased again in both ventricles and attained control values. IHA also produced significant structural changes in cardiac myosin, particularly in the rigaht ventricle. The changes were characterized by the formation of myosin aggregates with significantly lower ATPase activity that the myosin monomer. The time course and localization of structural and enzymatic changes in cardiac myosin corresponded to the morphological damage to the heart fibres.     

An anatomic basis for fetal right ventricular dominance and arterial pressure sensitivity

Fetal right ventricular dominance of flow and arterial pressure sensitivity were recently recognized but controversial findings. We investigated ventricular volumes, weights and dimensions in order to understand if there were anatomic differences between the ventricles which might explain these differential functional findings in the fetal sheep. Forty-four near term lambs and their hearts were weighed. Right and left ventricular free wall weights were not different. Volumes were measured by generating in vitro pressure-volume relations and by casting the two ventricles after fixation at equal, physiologic pressures. Right ventricular volume was greater than left ventricular volume by both techniques. Ventricular interaction and a restraining effect of the pericardium were present. Measurements of the fixed ventricles and their casts revealed the following: left ventricular wall thickness was slightly greater than right ventricular wall thickness; lateral ventricular diameters were not different but anteroposterior ventricular diameters were much greater in the right than left ventricle. Because of these findings, the right ventricular circumferential radii of curvature were greater than for the left ventricle as was the radius to wall thickness ratio. Greater right ventricular volume and radius to wall thickness ratio may be important factors in right ventricular flow dominance and greater sensitivity to arterial pressure.     

Regulation of cardiac adrenomedullin-mRNA in different stages of experimental heart failure

Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We measured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and overt heart failure in rats with two different sizes of aortocaval shunt. Left and right atrial AM-mRNA expressions were unchanged in both heart failure models. Similarly, left and right ventricular AM-mRNA expressions were unchanged in compensated heart failure. In overt heart failure, however, the AM-mRNA expression was significantly increased in the left ventricle (145+/-20 vs. 100+/-3% of control, p<0.05). The right ventricular AM-mRNA expression was significantly increased only in a subgroup of animals with pulmonary congestion (lung weight >2.0 g, 141+/-16 vs. 100+/-11% of control, p<0.05). Ventricular AM concentrations were elevated in both ventricles in overt heart failure. AM plasma concentrations were significantly higher in the subgroup with pulmonary congestion than in rats with compensated heart failure (496+/-95 vs. 143+/-7 pmol/l, p<0.01). These data indicate that ventricular AM-mRNA expression and AM concentrations were upregulated only in advanced stages of heart failure. However, the exact contribution of cardiac AM synthesis to the increased AM plasma levels remains to be established.     

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.     

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.     

Transmural distribution of glucose metabolizing enzymes across the left and the right ventricle heart walls in three different mammalian species

The transmural distribution of five glucose metabolizing enzymes (hexokinase; glucose-6-phosphate dehydrogenase; phosphofructokinase; aldolase; and lactate dehydrogenase) were explored in the left and in the right ventricle wall of rat, ox and pig hearts. The levels of most of these enzyme activities were different in the different animal species and (within the same species) in the two ventricles. Most of these enzyme activities were found to be non-uniformly distributed across the left (but not across the right) ventricle wall. Differences in the transmural distribution of enzyme activities were detected among the three examined mammalian species.     

Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation

Pulmonary hypertension, characterized by elevated pulmonary arterial pressure (PAP) and right ventricular hypertrophy, is caused by decreased atmospheric oxygen at high altitude. We hypothesized that maternal undernutrition programs right ventricle gene expression and sensitivity to increasing PAP at high altitude (2,183 m). On day 30 of gestation, forty Angus x Gelbvieh cows received diets to induce either gain (Control) or loss of body weight (Restricted) until day 125 of gestation. On day 126 of gestation, Restricted cows were realimented to achieve the same body weight as Controls by day 250. Parturition occurred naturally. PAP, which ranged from 40 to 114 mmHg, was determined in 15-mo-old steers from Control or Restricted cows before necropsy. At necropsy, hearts were collected from steers, separated into right and left ventricles, atria, and septa and weighed. Ventricular thickness was recorded. Eight Affymetrix bovine microarrays were screened [four high PAP (two Control and two Restricted) and four low PAP (two Control and two Restricted)] with right ventricle mRNA. This analysis revealed that pentraxin-related protein, interferon-related developmental regulator, and peroxisome proliferator-activated receptor-gamma coactivator-1alpha were differentially expressed (P < 0.05) in steer right ventricle from high-PAP cows compared with low-PAP cows. Also, activation peptide and pancreas cationic trypsinogen, alpha-actin, similar to ubiquitin carboxylesterase, were differently expressed (P < 0.05) in steers from Restricted cows compared with those from Control cows. Upregulated genes in high-PAP right ventricle have been associated with pathological cardiac hypertrophy. It is concluded that right ventricle gene expression may be differentially programmed by maternal undernutrition in the fetus during early gestation and may be detrimental to health and longevity of offspring, particularly at high altitude.     

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.     

Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of cardiomyopathy characterized by ventricular tachyarrhythmias and a fibrofatty infiltrate that is believed to preferentially affect the right ventricle. Mutations in the cardiac ryanodine receptor (RyR2) gene have been identified in some human families with a unique form of ARVC, ARVC2. Although the RyR2 has significant importance in excitation–contraction coupling across the ventricles, mutations in the gene encoding for it appear to have the greatest impact on the right ventricle in ARVC2. Using a canine model (boxer), the RyR2 protein and message RNA in the right ventricle, left ventricle and interventricular septum from normal dogs and dogs with ARVC were investigated by immunoblotting and real time PCR. The cardiac RyR2 message and protein expression were differentially expressed across the cardiac walls in the normal heart, with the lowest concentration expressed in the right ventricle (P < 0.05). The message and protein expression of the RyR2 were reduced in all chambers in the canine model of ARVC. We propose that the increased susceptibility of the right ventricle to ARVC may be associated with the lower baseline protein concentration of RyR2 in the normal right ventricle compared to the left ventricle and interventricular septum and that all three areas are equally affected in this canine model of ARVC. Using this naturally occurring model of canine ARVC, we may have provided new insights into the pathogenesis of this cardiomyopathy.     

Early alterations in myocardia and vessels of the diabetic rat heart: an FTIR microspectroscopic study

Diabetes mellitus is associated with a high incidence and poor prognosis of cardiovascular disease. The aim of the present study was to examine the effect of relatively short-term (5 weeks) Type I diabetes on the left ventricle, the right ventricle and the vessel (vein) on the left ventricle of the myocardium at molecular level by FTIR (Fourier-transform infrared) microspectroscopy. The rats were categorized into two groups: control group (for the left ventricle myocardium, n=8; for the right ventricle myocardium, n=9; for the vein, n=9) and streptozotocin-induced diabetic group (for the left ventricle myocardium, n=7; for the right ventricle myocardium, n=9; for the vein, n=8). Two adjacent cross-sections of 9 microm thickness were taken from the ventricles of the hearts in two groups of rats by using a cryotome. The first sections were used for FTIR microspectroscopy measurements. The second serial sections were stained by haematoxylin/eosin for comparative purposes. Diabetes caused an increase in the content of lipids, an alteration in protein profile with a decrease in alpha-helix and an increase in beta-sheet structure as well as an increase in glycogen and glycolipid contents in both ventricles and the vein. Additionally, the collagen content was found to be increased in the vein of the diabetic group. The present study demonstrated that diabetes-induced alterations in the rat heart can be detected by correlating the IR spectral changes with biochemical profiles in detail. The present study for the first time demonstrated the diabetes-induced alterations at molecular level in both ventricle myocardia and the veins in relatively short-term diabetes.     

Comparison of Doppler flow Tei-indexes with pulmonary artery thermodilution measurement of cardiac output in an experimental porcine model

The objective of our study was to compare Doppler echocardiography imaging with pulmonary artery thermodilution measurement during mechanical ventilation. Total 78 piglets (6 weeks old, average weight 24 kg, under general anesthesia) were divided into 4 groups under different cardiac loading conditions (at rest, with increased left ventricular afterload, with increased right ventricular preload, and with increased afterload of both heart ventricles). At 60 and 120 min the animals were examined by echocardiography and simultaneously pulmonary artery thermodilution was used to measure cardiac output. Tei-indexes data were compared with invasively monitored hemodynamic data and cardiac output values together with calculated vascular resistance indices. A total of 224 parallel measurements were obtained. Correlation was found between values of right Tei-index of myocardial performance and changes in right ventricular preload (p<0.05) and afterload (p<0.01). Significant correlation was also found between left index values and changes of left ventricular preload (p<0.001), afterload (p<0.001), stroke volume (p<0.01), and cardiac output (p<0.01). In conclusion, echocardiographic examination and determination of the global performance selectively for the right and left ventricle can be recommended as a suitable non-invasive supplement to the whole set of methods used for monitoring of circulation and cardiac performance.     

Right ventricular TNF resistance during endotoxemia: the differential effects on ventricular function

Right and left ventricular myocytes originate from different cellular progenitors; however, it is unknown whether these cells differ in their response to endotoxemia. We hypothesized that 1) the percentage of endotoxemic functional depression within the right ventricle (RV) would be smaller than that of the left ventricle; and 2) that better RV function would correlate with lower levels of right ventricular TNF production. Adult Sprague-Dawley rats were divided into right and left control and endotoxin groups. Controls received vehicle, while endotoxin groups received LPS at 20 mg/kg ip. Hearts were excised either 2 or 6 h after injection. Hearts excised at 2 h were assayed for TNF, IL-6, TNF receptor 1 (TNFR1), TNFR2, and via ELISA, while hearts excised at 6 h were assayed via the Langendorff model. The percentage of cardiac functional depression, exhibited as developed pressure, contractility, and rate of relaxation (expressed as a percentage of control) was significantly smaller in right ventricles compared with left ventricles following endotoxin exposure. Tissue levels of TNF were significantly elevated in both right and left ventricles 2 h after endotoxin exposure, and right ventricular endotoxin groups expressed higher levels of TNF compared with their left ventricular counterparts. No significant differences in IL-6, TNFR1, or TNFR2 levels were noted between endotoxin-exposed ventricles. This is the first study to demonstrate that right and left ventricular function differs after endotoxin exposure.     

Comparative analyses of the kinetics and subunits of myosins from canine skeletal muscle and cardiac tissue.

Two types of canine cardiac myosins, myosin from the free wall of the right ventricle and the free wall of the left ventricle, were compared with canine skeletal muscle myosin from the gastrocnemius. The Vmax values for the ATPase reaction catalyzed by myosin were significantly different among the three types of tissues. For K+-activated myosin the Vmax values in micromoles of Pi per mg per min were: right ventricle, 0.57; left ventricle, 0.72; and gastrocnemius, 0.95. For Ca-2+ -activated myosin the Vmax values were: right ventricle, 0.32; left ventricle, 0.42; gastrocnemius, 0.50. All differences were significant (p smaller than 0.001). For all three types of tissues the Vmax values for NH4+ -activated myosin were the same (2.30). Light chains among all three types of tissues were immunologically identical, whereas the heavy chains of the two cardiac ventricles were immunologically identical with each other; however both were immunologically nonidentical with those of the gastrocnemius. The proportion of myosin light chains to heavy chains was different in the three types of tissue. Of the total protein present in each of the myosins, there was 18% in the light chains of right ventricle myosin, 10% in the light chains of left ventricle myosin, and 13% in the light chains of gastrocnemius. Both left ventricle myosin and myosin from gastrocnemius had significantly less C1d light chain, as compared to myosin from the right ventricle.     

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT(1)) and type 2 (AT(2)) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT(1) and AT(2) expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase (P < 0.05) in AT(1) binding and AT(1) mRNA levels in the absence of any significant change in AT(2) expression level. Only after 14 days of hypoxia, AT(2) binding increased (P < 0.05) in the two ventricles, concomitantly with a right ventricular decrease (P < 0.05) in AT(2) mRNA. Along these data, AT(1) and AT(2) binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT(1) and AT(2) receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia.     

Metabolic acidosis decreases fetal myocardial isovolumic velocities in a chronic sheep model of increased placental vascular resistance

We hypothesized that acute fetal metabolic acidosis decreases fetal myocardial motion in a chronic sheep model of increased placental vascular resistance (R(ua)). Eleven ewes and fetuses were instrumented at 118-122 days of gestation. After 5 days of recovery and 24 h of placental embolization to increase R(ua), longitudinal myocardial velocities of the right and left ventricles and interventricular septum (IVS) were assessed at the level of the atrioventricular valve annuli via tissue Doppler imaging (TDI). Ventricular inflow (E and A waves) and outflow velocities were obtained, and cardiac outputs were calculated. All measurements were performed at baseline and during fetal acidosis caused by epidural anesthesia-induced maternal hypotension, which decreased uterine artery volume blood flow, fetal oxygenation, arterial pH, and base excess and increased lactate. Compared with baseline, the peak isovolumic myocardial contraction and relaxation velocities of the ventricles and IVS, early relaxation velocity (E') of the ventricles, and systolic velocity of the IVS decreased during metabolic acidosis. The proportion of isovolumic contraction time of the cardiac cycle increased but the isovolumic relaxation and ejection time proportions and the TDI Tei index did not change. The E-to-E' ratio for both ventricles was higher during metabolic acidosis than at baseline. During metabolic acidosis, right and left ventricular cardiac outputs remained unchanged compared with baseline. In sheep fetuses with increased R(ua) and acute metabolic acidosis, global cardiac function was preserved. However, acute metabolic acidosis impaired myocardial contractility during the isovolumic phase and relaxation during the isovolumic and early filling phases of the cardiac cycle.