Evaluation of the Right Ventricular Function in Pneumoconiosis Patients Using Volume–Time Curves Obtained by Real-Time Three-Dimensional Echocardiography

The study was aimed to evaluate the right ventricular function in pneumoconiosis patients by real-time three-dimensional echocardiography. A total of 80 individuals including 44 consecutive pneumoconiosis patients and 36 age- and gender-matched healthy volunteers as controls were prospectively recruited for the study. All the patients underwent two- and three-dimensional echocardiography. Measurements of the right ventricle included tricuspid regurgitation pressure (TRPG), anterior and posterior wall thickness and range of motion (TH1, TH2, M1, M2), right end-diastolic volume and end-systolic volume. The right ventricular ejection fraction (RVEF) was also calculated. The RVEF of healthy volunteers ranged from 50 to 78 %, whereas that of the pneumoconiosis patients varied from 29 to 73 %. An increase in TRPG caused a significant (p = 0.006) decrease in RVEF (by 77.3 %), suggesting the two variables were negatively correlated (r = ?0.643, p < 0.01). In comparison with normal, the volume–time curves of the pneumoconiosis patients showed a lower trough. Use of real-time three-dimensional echocardiography provides with added clinical information needed to evaluate right ventricular function in pneumoconiosis patients.     

Heat shock protein 27 is increased in cyanotic tetralogy of Fallot myocardium and is associated with improved cardiac output and contraction

Tetralogy of Fallot (TOF) is a congenital heart condition in which the right ventricle is exposed to cyanosis and pressure overload. Patients have an increased risk of right ventricle dysfunction following corrective surgery. Whether the cyanotic myocardium is less tolerant of injury compared to non-cyanotic is unclear. Heat shock proteins (HSPs) protect against cellular stresses. The aim of this study was to examine HSP 27 expression in the right ventricle resected from TOF patients and determine its relationship with right ventricle function and clinical outcome. Ten cyanotic and ten non-cyanotic patients were studied. Western blotting was used to quantify HSP 27 in resected myocardium at (1) baseline (first 15 min of aortic cross clamp and closest representation of pre-operative status) and (2) after 15 min during ischemia until surgery was complete. The cyanotic group had significantly increased haematocrit, lower O₂ saturation, thicker interventricular septal wall thickness and released more troponin-I on post-operative day 1 (p?<?0.05). HSP 27 expression was significantly increased in the <15 min cyanotic compared to the <15 min non-cyanotic group (p?=?0.03). In the cyanotic group, baseline HSP 27 expression also significantly correlated with oxygen extraction ratio (p?=?0.028), post-operative basal septal velocity (p?=?0.036) and mixed venous oxygen saturation (p?=?0.02), markers of improved cardiac output/contraction. Increased HSP 27 expression and associated improved right ventricle function and systemic perfusion supports a cardio-protective effect of HSP 27 in cyanotic TOF.     

The effect of aging and pressure on the specific hydraulic conductivity of the aortic wall

We measured the specific hydraulic conductivity (K) of the human and bovine aortic wall, two tissues for which K has not been previously reported in the literature, and examined the effects of aging (human) and development (bovine) on K. As part of the study, we also examined the effects of mounting the tissue in a flat or cylindrical configuration and the effects of perfusion pressure. With aging, in the human, we found a modest increase of K with age in a flat geometry; this trend was not apparent in a limited number of measurements in a cylindrical geometry. No significant dependence of K on developmental stage was found in the bovine aortic wall perfused in either a flat or cylindrical geometry. Our results indicate that aging and developmental changes of the aortic extracellular matrix have minimal effects on its hydrodynamic transport properties as measured. Mounting geometry for the aorta has been a concern reported in the literature since Yamartino et al. (1974) reported that K in the rabbit was 10-fold lower when measured in a flat geometry than in a cylindrical geometry. We found mounting geometry to make only a small difference in the calf and the cow, (K_flat approximately 2/3 of K_cylindrical), and in the human, we found K to be somewhat higher in the flat geometry than in the cylindrical geometry. Higher perfusion pressures decreased K of bovine tissue in the flat geometry, but pressure was not found to have a significant effect on K in the cylindrical geometry. An analytical model demonstrated that the anisotropic nature of the aortic wall allows it to be compressible (water-expressing) and yet remain at nearly constant tissue volume as the aorta is pressurized in a cylindrical geometry.     

A method for the measurement of left ventricular overload for aortic valve insufficiency

BackgroundThe degree of left ventricular overload in patients with aortic valve insufficiency (AI) plays an important role in determining the need and timing of surgical intervention. Because hemodynamic evaluation of AI may potentially predict the effects of an insufficient valve on the ventricle before they occur, it would be useful to guide valve surgery with such a diagnostic tool. The purpose of this study was to test the performance of a new hemodynamic index based on mechanical energy loss for the measurement of the effects of insufficiency on ventricular workload.Methods and resultsAn intact and subsequently perforated aortic bioprosthesis was tested within an in vitro model of the left heart, varying cardiac output, diastolic aortic pressure, and the size of perforation. Regurgitant orifice area (ROA), regurgitant volume (RV), regurgitant fraction (RF), and energy loss index (ELI) were measured for each experimental condition and plotted against the increase in workload per unit volume net forward flow (ΔWPV) due to perforation. ROA, RV, and RF showed good correlations with ΔWPV, but the relationship between these variables and ΔWPV became ambiguous as their magnitudes increased. ELI had a near perfect linear relationship with ΔWPV (slope=1.00, r²=0.98) independent of the experimental condition.ConclusionsRV, RF, and ROA do not by themselves fully describe the increase in difficulty the ventricle has in moving the blood across an insufficient valve. ELI, in contrast, was found to be a very good measure of the decrease in pump efficiency due to aortic valve insufficiency.     

Real-Time Three-Dimensional Echocardiography to Assess Right Ventricle Function in Patients with Pulmonary Hypertension

Background

The convenience and availability of real-time three-dimensional echocardiography (RT3DE) makes it an attractive candidate for assessing right ventricle function. However, the viability of RT3DE is not conclusive.

Aim of Study

This study aims to evaluate RT3DE relative to cardiac magnetic resonance and 2-dimensional echocardiography (2DE) for measuring right ventricular systolic function in patients with pulmonary hypertension.

Methods

Patients with pulmonary hypertension (n = 23) underwent cardiac magnetic resonance, 2DE, and RT3DE. Specifically, 2DE was used to measure the right ventricular index of myocardial performance (RIMP), fractional area change, tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler-derived tricuspid annular systolic velocity (S′). Cardiac magnetic resonance and RT3DE were used to measure right ventricular end-diastolic volume (RVEDV) and end-systolic volume (RVESV). The right ventricular ejection fraction (RVEF) was calculated.

Results

Regarding the measurements taken by 2DE, RVEF positively correlated with fractional area change (r = 0.595, P = 0.003) and S′(r = 0.489, P = 0.018), and negatively correlated with RIMP (r = −0.745, P = 0.000). There was no association between RVEF and TAPSE (r = −0.029, P = 0.896). There existed a close correlation between the values of RVEDV, RVESV, and RVEF as measured by RT3DE and CMR respectively (P<0.001); Bland-Altmanan analyses showed good agreement between them.

Conclusion

RT3DE was a viable method for noninvasive, accurate assessment of right ventricular systolic function in patients with pulmonary hypertension.     

A METHOD FOR THE STUDY OF CHOLESTEROL BIOSYNTHESIS IN THE CENTRAL NERVOUS SYSTEM

Abstract—

• 1 After intraperitoneal injection, there is negligible incorporation of [2-¹⁴C]-mevalonic lactone into the CNS of the adult rat.
• 2 Mevalonic lactone injected into the CSF is quickly transferred to blood.
• 3 Mevalonic lactone injected in the cistema magna or the lateral ventricle of the brain does not diffuse readily into the whole CSF. Spinal cord cholesterol is most heavily labelled after intracisternal injection, as is brain cholesterol after intraventricular administration.
• 4 After intraventricular perfusion, the diffusion of mevalonic lactone into the ventricle opposite the side of the injection is increased when the rate of perfusion is doubled from 5 to 10 μ1/hr. After injection, optimal homogeneity is obtained if a large volume (70μl) is administered.
• 5 An increase in the volume of injection from 70 μl to 130μl does not alter the distribution of activity between the left and right ventricles, nor does it increase the diffusion of mevalonic lactone from ventricle to spinal cord CSF.
• 6 The mean yield of mevalonic lactone incorporation into brain cholesterol is much higher after injection than after perfusion of precursor into the lateral cerebral ventricle.

     

Développement et évaluation d’un algorithme de segmentation automatisée des ventricules gauche et droit sur des images ciné d’IRM

An automated segmentation of the left and right ventricles on cine MRI is presented here. A rectangular region around the object of interest is defined in the original image, a morphological filter is then applied that combines openings and closings on connected sets, providing an image with homogeneous regions, which is finally segmented with an active contour model. The algorithm was tested on two databases with an expert's segmentation on the ventricles. One of the databases was provided by the Multicentric Initiative for a Platform of Evaluation in Cardiac Imaging (IMPEIC) group. Results show a very satisfactory correlation between the area (given in mm²) of expertise (x) and the area of automated segmentation (y) of the left ventricle (y = 1.00x + 8.6, r = 0.99). First results on the right ventricle show more than 83% similarity. The systolic phase proved to be more difficult to segment, which could be taken into consideration by introducing time regularization criteria in the algorithm.     

Beta-Blockers,Left and Right Ventricular Function,and In-Vivo Calcium Influx in Muscular Dystrophy Cardiomyopathy

Beta-blockers are used to treat acquired heart failure in adults, though their role in early muscular dystrophy cardiomyopathy is unclear. We treated 2 different dystrophic mouse models which have an associated cardiomyopathy (mdx: model for Duchenne Muscular Dystrophy, and Sgcd-/-: model for limb girdle muscular dystrophy type 2F) and wild type controls (C57 Bl10) with the beta blocker metoprolol or placebo for 8 weeks at an early stage in the development of the cardiomyopathy. Left and right ventricular function was assessed with cardiac magnetic resonance imaging (MRI) and in-vivo myocardial calcium influx with manganese enhanced MRI. In the mdx mice at baseline there was reduced stroke volume, cardiac index, and end-diastolic volume with preserved left ventricular ejection fraction. These abnormalities were no longer evident after treatment with beta-blockers. Right ventricular ejection fraction was reduced and right ventricular end-systolic volume increased in the mdx mice. With metoprolol there was an increase in right ventricular end-diastolic and end-systolic volumes. Left and right ventricular function was normal in the Sgcd-/- mice. Metroprolol had no significant effects on left and right ventricular function in these mice, though heart/body weight ratios increased after treatment. In-vivo myocardial calcium influx with MEMRI was significantly elevated in both models, though metoprolol had no significant effects on either. In conclusion, metoprolol treatment at an early stage in the development of cardiomyopathy has deleterious effects on right ventricular function in mdx mice and in both models no effect on increased in-vivo calcium influx. This suggests that clinical trials need to carefully monitor not just left ventricular function but also right ventricular function and other aspects of myocardial metabolism.     

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output (r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes (P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.     

Auxiliary diagnostic potential of ventricle geometry and late gadolinium enhancement in left ventricular non-compaction; non-randomized case control study

Background

There are still ambiguities existing in regard to left ventricular non-compaction (LVNC) diagnostic imaging. The aim of our study was to analyze diagnostic potential of late gadolinium enhancement (LGE) and ventricle geometry in patients with LVNC and controls.

Methods

Data on cardiac magnetic resonance imaging (CMR) studies for LVNC were reassessed from the hospital’s database (3.75 years; n=1975 exams). Matching sample of controls included cases with no structural heart disease, hypertrophic or dilative cardiomyopathy, arrhythmogenic right ventricular dysplasia or subacute myocarditis. Eccentricity of the left ventricle was measured at end diastole in the region with pronounced NC and maximal to minimal ratio (MaxMinEDDR) was calculated.

Results

Study included 255 patients referred for CMR, 100 (39.2%) with LVNC (prevalence in the studied period 5.01%) and 155 (60.8%) controls. Existing LGE had sensitivity of 52.5% (95%-CI:42.3–62.5), specificity of 80.4% (95%-CI:73.2–86.5) for LVNC, area under curve (AUC) 0.664 (95%-CI:0.603–0.722);p<0.001. MaxMinEDDR>1.10 had sensitivity of 95.0% (95%-CI:88.7–98.4), specificity of 82.6% (95%-CI: 75.7–88.2) for LVNC, AUC 0.917 (95%-CI:0.876–0.948); p<0.001. LGE correlated with Max-Min-EDD-R (Rho=0.130; p=0.038) and there was significant difference in ROC analysis ΔAUC0.244 (95%-CI:0.175–0.314); p<0.001. LGE also correlated negatively with stroke volume and systolic function (both p<0.05, respectively).

Conclusions

LGE was found to be frequently expressed in patients with LVNC, but without sufficient power to be used as a discriminative diagnostic parameter. Both LGE and eccentricity of the left ventricle were found to be relatively solid diagnostic landmarks of complex infrastructural and functional changes within the failing heart.

     

Flow studies on atriopulmonary and cavopulmonary connections of the Fontan operations for congenital heart defects

A comparative flow study has been conducted on two configurations of the Fontan operations for congenital heart defects in which the right ventricle is by-passed. The study was made on rigid in vitro models of the atriopulmonary and cavopulmonary connections under steady-flow conditions. It involved using pressure and flow measurements to determine the pressure-drop coefficient, pressure-energy-loss coefficient and total-energy-loss coefficient. The cavopulmonary model was found to have much lower flow losses compared to the atriopulmonary model, especially at flow rates about 5 l min⁻¹     

Average thickness of the gas vesicle wall in Anabaena flos-aquae.

The average thickness of the layer of protein which forms the wall of the gas vesicles in Anabaena flos-aquae was estimated from measurements of their density and geometry. The volume of the gas space in a purified gas vesicle suspension was determined from the contraction which occurred when the gas vesicles were collapsed by pressure. The volume of the protein in the same sample was calculated from its dry weight and density. From knowledge of the geometry of the average gas vesicle the thickness of the protein layer, 1.54 nm, was then calculated. By a similar method the thickness of the Microcystis gas vesicle wall, 1.62 nm, was calculated from data published by others. The average thickness of the protein layer is, as expected, slightly less than the stacking periodicity of collapsed gas vesicle walls indicated by X-ray diffraction studies.Anabaena gas vesicles with a mean length of 494 nm have an average density of 0.119 mg μl^?1 1 mg of protein is present in gas vesicles having a, total volume of 8.43 μl and a gas space of 7.67 μl. Suspensions of isolated gas vesicles with a gas space concentration of 1 μl ml^?1 give a pressure-sensitive optical density, E_1cm (500 nm) of 2.72, but gas vacuoles in cells give a smaller value.     

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.     

Up-regulation of hexokinase1 in the right ventricle of monocrotaline induced pulmonary hypertension

Background

Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with a glycolytic shift during heart metabolism. An increase in glycolytic metabolism can be detected in the right ventricle during PAH. Expression levels of glycolysis genes in the right ventricle during glycolysis that occur in monocrotaline (MCT)-induced pulmonary hypertension (PH) remain unknown.

Methods

PH was induced by a single subcutaneous injection of MCT (50 mg/kg) into rats, eventually causing right heart failure. Concurrently, a control group was injected with normal saline. The MCT-PH rats were randomly divided into three groups according to MCT treatment: MCT-2 week, 3 week, and 4 week groups (MCT-2w, 3w, 4w). At the end of the study, hemodynamics and right ventricular hypertrophy were compared among experimental groups. Expression of key glycolytic candidate genes was screened in the right ventricle.

Results

We observed an increase in mean pulmonary arterial pressure, right ventricular systolic pressure and right ventricular hypertrophy index three weeks following MCT injection. Alterations in the morphology and structure of right ventricular myocardial cells, as well as the pulmonary vasculature were observed. Expression of hexokinase 1 (HK1) mRNA began to increase in the right ventricle of the MCT-3w group and MCT-4w group, while the expression of lactate dehydrogenase A (LDHA) was elevated in the right ventricle of the MCT-4w group. Hexokinase 2(HK2), pyruvate dehydrogenase complex α1 (PDHα1), and LDHA mRNA expression showed no changes in the right ventricle. HK1 mRNA expression was further confirmed by HK1 protein expression and immunohistochemical analyses. All findings underlie the glycolytic phenotype in the right ventricle.

Conclusions

There was an increase in the protein and mRNA expression of hexokinase-1 (HK1) three and four weeks after the injection of monocrotaline in the right ventricle, intervention of HK1 may be amenable to therapeutic intervention.     

Mechanisms of Transition from Normal to Reentrant Electrical Activity in a Model of Rabbit Atrial Tissue: Interaction of Tissue Heterogeneity and Anisotropy

Experimental evidence suggests that regional differences in action potential (AP) morphology can provide a substrate for initiation and maintenance of reentrant arrhythmias in the right atrium (RA), but the relationships between the complex electrophysiological and anatomical organization of the RA and the genesis of reentry are unclear. In this study, a biophysically detailed three-dimensional computer model of the right atrial tissue was constructed to study the role of tissue heterogeneity and anisotropy in arrhythmogenesis. The model of Lindblad et al. for a rabbit atrial cell was modified to incorporate experimental data on regional differences in several ionic currents (primarily, I_Na, I_CaL, I_K1, I_to, and I_sus) between the crista terminalis and pectinate muscle cells. The modified model was validated by its ability to reproduce the AP properties measured experimentally. The anatomical model of the rabbit RA (including tissue geometry and fiber orientation) was based on a recent histological reconstruction. Simulations with the resultant electrophysiologically and anatomically detailed three-dimensional model show that complex organization of the RA tissue causes breakdown of regular AP conduction patterns at high pacing rates (>11.75 Hz): as the AP in the crista terminalis cells is longer, and electrotonic coupling transverse to fibers of the crista terminalis is weak, high-frequency pacing at the border between the crista terminalis and pectinate muscles results in a unidirectional conduction block toward the crista terminalis and generation of reentry. Contributions of the tissue heterogeneity and anisotropy to reentry initiation mechanisms are quantified by measuring action potential duration (APD) gradients at the border between the crista terminalis and pectinate muscles: the APD gradients are high in areas where both heterogeneity and anisotropy are high, such that intrinsic APD differences are not diminished by electrotonic interactions. Thus, our detailed computer model reconstructs complex electrical activity in the RA, and provides new insights into the mechanisms of transition from focal atrial tachycardia into reentry.     

Echocardiographic evaluation of delayed outcome of artificial valve implantation in patients with aortic semilunar valve insufficiency]

An average follow-up period of 16 patients was 28 months following an implantation of the artificial aortic valve for its insufficiency. In 10 operated patients who were able to continue their occupation exercise tolerance increased by two classes, according to NYHA. Blood pressure gradient decreased significantly from 61.8 to 37.5 mmHg, cardiac volume index decreased from 639 to 602 ml/m2. Echocardiographically measured muscle mass of the left ventricle, end-diastolic and end-systolic volumes, and the left atrial dimensions decreased significantly following surgery. A significance of the relation of the left ventricle volume to its mass <4 as a prognostic factor in aortic valve replacement has also been confirmed.     

Oxygen supply in disposable shake-flasks: prediction of oxygen transfer rate, oxygen saturation and maximum cell concentration during aerobic growth

Dissolved oxygen plays an essential role in aerobic cultivation especially due to its low solubility. Under unfavorable conditions of mixing and vessel geometry it can become limiting. This, however, is difficult to predict and thus the right choice for an optimal experimental set-up is challenging. To overcome this, we developed a method which allows a robust prediction of the dissolved oxygen concentration during aerobic growth. This integrates newly established mathematical correlations for the determination of the volumetric gas–liquid mass transfer coefficient (k_La) in disposable shake-flasks from the filling volume, the vessel size and the agitation speed. Tested for the industrial production organism Corynebacterium glutamicum, this enabled a reliable design of culture conditions and allowed to predict the maximum possible cell concentration without oxygen limitation.