Ventricle Systolic Pressure Research Articles

Apical Sparing of Longitudinal Strain, Left Ventricular Rotational Abnormalities, and Short-Axis Dysfunctionin Primary Hyperoxaluria Type 1

A 24-year-old woman with end-stage renal failure because of primary hyperoxaluria type 1 was evaluated in our hospital for systemic calcium oxalate deposition in the course of long-term (5 years) hemodialysis therapy. Diagnosis of primary hyperoxaluria type 1, a hereditary cause of calcium oxalate kidney stones or progressive nephrocalcinosis that frequently results in end-stage renal failure,1 was made by liver biopsy (reduced alanine:glyoxylate aminotransferase activity, 3.0 µmol/h per milligram protein; normal, 19.1–47.9) and by genetic testing (homozygosity for the c.302 T>C, AGXT mutation). Her plasma oxalate level on regular hemodialysis (3× per week over 4 hours) was increased (86 µmol/L predialysis; normal, <10 µmol/L). Transthoracic echocardiography revealed increased wall thickness of the left ventricle (LV; Figure 1). The LV was mildly dilated and showed a decreased systolic function. Flow across the mitral valve demonstrated a restrictive filling pattern. Moreover, the myocardium had a characteristic echo-dense granular sparkling appearance (Movie in the online-only Data Supplement).2 Both atria were enlarged. Moderate tricuspid regurgitation was present. A right ventricle systolic pressure of 62 …

Pde3a‐deficient mice have evidence of pulmonary hypertension

Pulmonary hypertension (PH) is associated with vasoconstriction and vascular remodeling characterized by pulmonary artery smooth muscle cell (PASMC) proliferation. In vitro, human PASMC proliferation requires arginase II (arg II) and cAMP elevating agents prevent hypoxia‐induced arg II induction. We hypothesized that Pde3a‐deficient mice have attenuated PH. Pde3a−/− (KO) and wild type (WT) mice were exposed to 21%O2 (normoxia) or 10%O2 (hypoxia) for 28d. Right ventricle systolic pressure (RVSP) was measured. 2D echocardiography was used to measure pulmonary acceleration time/ejection time (PAT/PET). The mice were sacrificed; lungs and hearts were harvested. RV and left ventricle (LV)+septum (S) were weighed and ratio of RV/(LV+S) weights calculated. Lung arg II and cAMP levels were measured. KO mice had higher RVSP, lower PAT/PET ratios, and higher RV/(LV+S) ratios compared to WT mice. KO mice had greater lung cAMP, but arg II protein levels did not differ from WT mice. Interestingly, KO mice exposed to hypoxia had similar RVSP, PAT/PET and RV/(LV+S) ratios as hypoxia‐exposed WT mice. Pde3a‐deficient mice have evidence of PH as seen by RVSP, PAT/PET and RV/(LV+S) ratios. Interestingly, hypoxia exposure did not result in any worsening of PH in KO mice. Our data suggest that alterations in Pde3a gene function may underlie forms of PH not associated with hypoxia, such as primary pulmonary arterial hypertension.

Hypoxia-inducible factor-1α and vascular endothelial growth factor in the cardioprotective effects of intermittent hypoxia in rats

Objective. This study investigated the effects of short-term intermittent hypoxia (IH) preconditioning on cardiac structure and function in rats and the influence of ischemia reperfusion (I/R) injury. Special attention was then paid to the involvement of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF).Methods. Wistar rats were given IH treatment for 1, 7, 14, or 28 days. Some of them were thereafter subject to myocardial infarction surgery. Right ventricle systolic pressure (RVSP), myocardial capillary density (CD), and mRNA/protein expression of HIF-1α, VEGF, and Bcl-2 in rat myocardial tissue were determined. Apoptotic cell number was determined by TUNEL staining, and concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured.Results. IH treatment for 1, 7, 14, and 28 days reduced the myocardial infarction size, whereas IH for 28 days increased the RVSP, ratio of right to left ventricle weight (RV/LV+S), and CD. IH up-regulated the mRNA and protein levels of HIF-1α, VEGF, and Bcl-2 both under normal and I/R conditions. The induced expression of HIF-1α and VEGF by IH reached a peak after 7 days of treatment. Moreover, IH for 28 days induced cardiomyocyte apoptosis, whereas prior treatment with IH for 1, 7, 14, and 28 days all markedly attenuated the apoptosis effected by the subsequent I/R injury. IH also decreased the concentrations of MDA but increased those of SOD in myocardial tissue of both in normal rats and following I/R.Conclusions. The present study demonstrates that short-term IH protects the heart from I/R injury through inhibiting apoptosis and oxidative stress. The up-regulation of HIF-1α and VEGF by short-term IH may participate in the cardioprotective effect of IH.

Primary pulmonary hypertension during pregnancy: A case report

We describe a case of a 25-year-old pregnant woman who presented with severe primary pulmonary hypertension (PPH). Her echocardiogram showed severe right ventricular hypertrophy with dilatation and Moderate right ventricular systolic dysfunction. Right ventricle systolic pressure (RVSP) was estimated to be 125mmHg. She had an elective caesarean section under general anaesthesia at 32weeks of gestation. Pulmonary artery pressures measured by a pulmonary artery catheter before anaesthesia were 102mmHg and pulmonary vascular resistance was 429. Intraoperative nitric oxide was used to reduce pulmonary artery systolic pressure (PASP). After the delivery of a healthy infant, PASP was controlled with nebulized iloprost and silandifil. Five days later she was transferred from intensive care unit after she was started on silandifil 50mg three times daily and a small dose of warfarin.

Influence of disease-related heart pathology on peak oxygen uptake and ventilation/carbon dioxide output ratio in systemic sclerosis and systemic lupus erythematosus patients (RCD code: I-3C)

Background: Exercise capacity is an independent predictor of mortality in the general population. However, available literature has been focused mainly on exercise testing in patients with ischaemic heart failure. Little is known about such testing in generalized autoimmune diseases with their different pathogenesis and sex prevalence. The aim of the study was to assess the influence of disease‑related heart pathology on exercise capacity evaluated by cardiopulmonary exercise (CPX) test in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients. Methods: Echocardiography and CPX test were performed in 46 SSc patients, 60 SLE patients and 30 healthy controls. Results: Echocardiography showed normal left ventricle systolic function in all subjects except for 2 (3,3%) SLE patients with enlarged left ventricle. In contrast, diastolic left ventricular dysfunction was found in all SSc patients and in 13 (21,7%) SLE patients. Right ventricle systolic pressures were elevated (&gt;30 mmHg) in 14 (30,4%) SSc and 10 (16,7%) SLE patients. Valvular leaflet or pericardium thickening was observed in 17 (37,0%) SSc and in 38 (63,3%) SLE patients. CPX test showed low exercise capacity in 36 (78,3%) SSc patients, while mean values of gas exchange parameters remained normal in SLE and control groups. In SSc time of exercise was significantly shorter and peak oxygen uptake decreased as compared to healthy subjects (13,1 ±4,8 min vs. 17,8 ±2,6 min, p = 0,01 and 16,51 ±6,86 ml/kg/min vs. 25,66 ±6,62 ml/kg/min, p = 0,001, respectively). Ventilation/carbon dioxide output ratio (VE/VCO2) was increased (&gt;34) in 32 (69,6%) SSc and 4 (6,7%) SLE patients. Weber C or D class of cardiopulmonary failure (severe or end‑stage, VO2peak &lt; 15 ml/kg/min) was observed in 20 (43,5%) SSc and only in 2 (3,4%) SLE patients. Conclusions: Exercise intolerance expressed by VO2peak &lt; 15 ml/kg/min and VE/VCO2 &gt; 34 was present in almost half of SSc patients, while severely impaired gas exchange parameters were very rare in SLE. Exercise capacity test may then serve as an important non‑invasive prognostic parameter in SSc. In contrast, in SLE prognostic value of CPX would be probably of lesser clinical importance as its abnormal values seem to be rare in this entity. JRCD 2013; 1 (3): 10–16

IL-13 receptor α2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension

Although previous literature suggests that interleukin (IL)-13, a T-helper type 2 cell effector cytokine, might be involved in the pathogenesis of pulmonary hypertension (PH), direct proof is lacking. Furthermore, a potential mechanism underlying IL-13-induced PH has never been explored. This study's goal was to investigate the role and mechanism of IL-13 in the pathogenesis of PH. Lung-specific IL-13-overexpressing transgenic (Tg) mice were examined for hemodynamic changes and pulmonary vascular remodeling. IL-13 Tg mice spontaneously developed PH phenotype by the age of 2 mo with increased expression and activity of arginase 2 (Arg2). The role of Arg2 in the development of IL-13-stimulated PH was further investigated using Arg2 and IL-13 receptor α2 (Rα2) null mutant mice and the small-interfering RNA (siRNA)-silencing approach in vivo and in vitro, respectively. IL-13-stimulated medial thickening of pulmonary arteries and right ventricle systolic pressure were significantly decreased in the IL-13 Tg mice with Arg2 null mutation. On the other hand, the production of nitric oxide was further increased in the lungs of these mice. In our in vitro evaluations, the recombinant IL-13 treatment significantly enhanced the proliferation of human pulmonary artery smooth muscle cells in an Arg2-dependent manner. The IL-13-stimulated cellular proliferation and the expression of Arg2 in hpaSMC were markedly decreased with IL-13Rα2 siRNA silencing. Our studies demonstrate that IL-13 contributes to the development of PH via an IL-13Rα2-Arg2-dependent pathway. The intervention of this pathway could be a potential therapeutic target in pulmonary arterial hypertension.

Deleterious Effect of Hypothermia in Myocardial Protection Against Cold Ischemia: A Comparative Study in Isolated Rat Hearts

BackgroundThere is a growing need to improve heart preservation benefit the performance of cardiac operations, decrease morbidity, and more important, increase the donor pool. Therefore, the objective of this study was to evaluate the cardioprotective effects of Krebs-Henseleit buffer (KHB), Bretschneider-HTK (HTK), St. Thomas No. 1 (STH-1), and Celsior (CEL) solutions infused at 10°C and 20°C. MethodsHearts isolated from male albino Wistar rats and prepared according to Langendorff were randomly divided equally into 8 groups according to the temperature of infusion (10°C or 20°C) and cardioprotective solutions (KHB, HTK, STH-1, and CEL). After stabilization with KHB at 37°C, baseline values were collected (control) for heart rate (HR), left ventricle systolic pressure (LVSP), coronary flow (CF), maximum rate of rise of left ventricular pressure during ventricular contraction (+dP/dt) and maximum rate of fall of left ventricular pressure during left ventricular relaxation (−dP/dt). The hearts were then perfused with cardioprotective solutions for 5 minutes and kept for 2 hours in static ischemia at 20°C. Data evaluation used analysis of variance (ANOVA) in all together randomized 2-way ANOVA and Tukey's test for multiple comparisons. The level of significance chosen was P < .05. ResultsWe observed that all 4 solutions were able to recover HR, independent of temperature. Interestingly, STH-1 solution at 20°C showed HR above baseline throughout the experiment. An evaluation of the corresponding hemodynamic values (LVSP, +dP/dt, and −dP/dt) indicated that treatment with CEL solution was superior at both temperatures compared with the other solutions, and had better performance at 20°C. When analyzing performance on CF maintenance, we observed that it was temperature dependent. However, when applying both HTK and CEL, at 10°C and 20°C respectively, indicated better protection against development of tissue edema. Multiple comparisons between treatments and hemodynamic variable outcomes showed that using CEL solution resulted in significant improvement compared with the other solutions at both temperatures. ConclusionThe solutions investigated were not able to fully suppress the deleterious effects of ischemia and reperfusion of the heart. However, these results allow us to conclude that temperature and the cardioprotective solution are interdependent as far as myocardial protection. Although CEL solution is the best for in myocardial protection, more studies are needed to understand the interaction between temperature and perfusion solution used. This will lead to development of better and more efficient cardioprotective methods.

Iptakalim Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

We sought to investigate the experimental therapeutic effects and mechanisms of iptakalim, a new adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) opener, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right heart ventricle remodeling in rats. Rats were injected with a single dose (50 mg/kg, ip) of MCT and given iptakalim (1, 3, and 9 mg/kg·per d, orally [po]) or saline for 28 days. The hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. Treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg from the day of MCT injection attenuated the high right ventricle systolic pressure (RVSP) and the increased weight ratio of right ventricle (RV) to left ventricle (LV) plus septum (S) (RV/(LV+S)), decreased heart rate (HR) and decreased mean arterial pressure (MAP), inhibited the RV myocardial tissue cell apoptosis, and the RV myocardial cell B-type natriuretic peptide (BNP) protein expression. Iptakalim also decreased the serum levels of nitric oxide (NO), endothelin 1 (ET-1), BNP, and the levels of NO, ET-1, and tumor necrosis factor-alpha (TNF-α) in the lung tissue. These results indicate that iptakalim prevents MCT-induced PAH and RV remodeling and its mechanisms are related to inhibiting the pathological increases in NO, ET-1, BNP, and TNF-α, and Iptakalim may be a promising candidate for the treatment of PAH.

089 Mice Are Resistant to the Development of Pulmonary Arterial Hypertension After SU5416-Induced Endothelial Apoptosis and Chronic Hypoxia Despite Altering Background and Dose

Pulmonary arterial hypertension (PAH) is believed to result from pulmonary endothelial cell (EC) injury and apoptosis followed by reactive vascular cell proliferation leading to obliteration of distal lung arterioles. SU5416 (SU) inhibits VEGFR2 causing EC apoptosis and, with chronic hypoxia (CH), severe PAH in rats. Moreover, athymic (nude) rats, lacking mature T-cells, exhibit severe PAH in response to SU5416, even in the absence of CH. Therefore, the aim of this study was to assess the susceptibility of wild type (WT) and athymic mice to SU and CH-induced severe PAH. Wild type C57Bl6/J mice were exposed to normoxia (N) or chronic hypoxia (CH) (9-10% O2), combined with a single injection of 20mg/kg SU5416 (SU), or multiple injections (3 or 6). Athymic nude mice (B6.Cg-Foxn1nu/J on C57Bl6/J background) were exposed to three weeks of CH combined with 3 SU injections (20mg/kg). To confirm the activity of the SU compound, Sprague-Dawley rats were treated with a single dose of SU and 3 weeks of CH. Hemodynamic assessments and lung tissue collection were performed at three weeks. In WT mice, CH induced a significant increase in right ventricle systolic pressure (RVSP) compared with N (38.2±2.3 vs. 25.4±1.2 mmHg, respectively; p<0.0001 n=8-9/group) and greater RV remodeling (RV/LV+S weight ratio 0.36±0.01 vs. 0.26±0.01, respectively; p<0.001 n=9/group). However, the administration of SU+CH failed to increase the PAH phenotype regardless of dose (1, 3 or 6 SU injections), assessed either by RVSP (43.1±1.2, 40.1±2.5, and 32.7±1.2 mmHg, respectively; n=5-9/group) or RV hypertrophy (0.4±0.01, 0.39±0.02, 0.45±0.03, respectively; n=5-10/group). Moreover, compared to CH alone, treatment of athymic mice with CH+SU did not increase RVSP (31.1±2 CH+SU vs. 29.9±1.0 CH, n=3) or RV remodeling (0.39±0.01 CH+SU vs. 0.42±0.01 CH, n=3). In contrast, in rats, SU+CH resulted in marked exaggeration of PAH compared with CH alone: RVSP (80.0±8.2 vs. 40±2mmHg, respectively); RV hypertrophy (0.56±0.34 and 0.33±0.1, respectively, all p< 0.001). Finally, despite the demonstration of EC apoptosis, there was no evidence of proliferative, intimal lesions in lungs of SU-CH treated WT or nude mice; whereas, typical obliterative, plexiform lesions were seen in the rat model. We now show for the first time that unlike rats, mice are highly resistant to PAH induced by EC apoptosis using SU5416, even in a T-cell deficient background and with up to 6 doses of SU, suggesting a fundamental difference in the response to vascular injury between these two species.

496 Transgenic Mice Lacking Sirt1 Catalytic Activity Exhibit Greater Susceptibility to Pulmonary Hypertension in Response to Chronic Hypoxia

Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary artery pressure, leading to right ventricle hypertrophy and ultimately heart failure and death. Pulmonary endothelial cell (EC) injury and apoptosis appear to be triggers for reactive vascular cell proliferation leading to narrowing and obliteration of distal lung arterioles. Sirt1 is a NAD+dependent deacetylase that has been strongly implicated in maintaining EC homeostasis in systemic vessels, but little is known about its role in the lung vasculature. The purpose of this study was to investigate the role of Sirt1 catalytic activity in PH. Sirt1Y/Y (H355Y point mutation) animals possess a Sirt1 protein lacking catalytic activity. Exposure of mutants (Sirt1Y/Y) to simulated normobaric hypoxia (9-10% O2) for 3 weeks resulted in a significant increase in right ventricle systolic pressure (RVSP) compared to their WT littermates exposed to the same conditions (42.9±2.3Sirt1Y/Y vs. 28.8±1.3WT; n=9 and 12 respectively, p<0.001, Figure 1 below). Furthermore, mutant animals showed significantly greater RV remodeling, measured by the RV/LV+S weight ratio (0.55±0.03 Sirt1Y/Y vs. 0.40±0.01 WT, p< 0.001) compared to the wild type littermates. In addition, hypoxia-induced pulmonary smooth muscle cell hyperplasia and perivascular cell infiltration seemed to be exacerbated in the mutant mice. Sirt1 protects against hypoxia-induced PH. This protection is most likely mediated through its well described role in maintenance of endothelial function and inhibition of apoptosis in response to stressors such as hypoxia.

Factors influencing left atrial volume in treated hypertension

BackgroundLeft atrial (LA) enlargement has been documented to occur in hypertension (HT), and has been an index for evaluating the diastolic function of the left ventricle. Enlargement of the LA is one of the vital factors that induce heart failure and atrial fibrillation (AF) in patients with HT. Methods and subjects130 treated hypertensive patients were enrolled. All recruits participated in an echocardiogram, electrocardiogram, a routine blood examination including brain natriuretic peptide (BNP), and physical examinations. ResultsLeft ventricular mass (LVM) indexed to height2.7 had a significant positive correlation with left atrial volume index (LAVI) (p<0.0001), as well as natural logarithm BNP (p<0.001). Blood pressure levels were not associated with LAVI, neither body mass index nor age. LAVI had a positive correlation with factors involving the left ventricle volume, LVM, and right ventricle systolic pressure (RVSP) (r=0.687, p<0.0001). The parameters of LV diastolic function were positively but weakly associated with LA size. In the subgroup of LAVI, the evidence of paroxysmal atrial fibrillation (PAF): LAVI<32ml/m2 had no PAF, whereas the incidence of PAF was 7.5%, 11.4%, and 15.2%, respectively in the LAVI>32ml/m2 group. Of anti-hypertension drugs, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers had a tendency to reduce LAVI; however, there was no statistical significance within the groups. ConclusionsLeft ventricular volume and mass are independent factors affecting LAVI in treated HT. The incidence of PAF is associated with LA size. In patients with treated HT, LA size may be a useful surrogate marker for monitoring the effectiveness of medical therapy and occurrence of AF.

487 Oral Sildenafil: A Safe and Effective Treatment of Persistent Pulmonary Hypertension after Heart Transplantation

Among heart transplantation (HT) patients, pre-HT pulmonary hypertension (PH), is an independent predictor of mortality. Treatment options are limited. Perioperative administration of sildenafil may prevent right ventricular failure in HT recipients with persistent PH after HT. Aim: To evaluate the effects of chronic sildenafil use on right ventricle systolic pressure (RVSP) and the safety of this therapy.

Inhibitory effect of calcitonin gene-related peptide on hypoxia-induced rat pulmonary artery smooth muscle cells proliferation: Role of ERK1/2 and p27

Calcitonin gene-related peptide (CGRP) inhibits angiotensin II-induced proliferation of aortic smooth muscle cells via inactivation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). ERK1/2 is necessary for the degradation or down-regulation of the cell cycle inhibitor p27, and is also crucial in mediating proliferation of pulmonary artery smooth muscle cells (PASMCs). Whether ERK1/2/p27 signal pathway is involved in CGRP-mediated pathogenesis of pulmonary hypertension and vascular remodeling remains unknown. Pulmonary hypertension was induced by hypoxia in rats, and capsaicin (50mg/kg, s.c.) was used to deplete endogenous CGRP. Proliferation of cultured PASMCs was determined by BrdU incorporation method and flow cytometry. The expression/level of CGRP, p27, ERK1/2, c-fos and c-myc was analyzed by radioimmunoassay, immunohistochemistry, real-time PCR or Western blot. Sensory CGRP depletion by capsaicin exacerbated hypoxia-induced pulmonary hypertension in rats, as shown by an increase in right ventricle systolic pressure, mean pulmonary artery pressure and vascular hypertrophy, accompanied with decreased p27 expression and increased expression of phosphorylated ERK1/2, c-fos and c-myc. Exogenous application of CGRP significantly inhibited hypoxia-induced proliferation of PASMCs concomitantly with increased p27 expression and decreased expression of phosphorylated ERK1/2, c-fos and c-myc. These effects of CGRP were abolished in the presence of CGRP8–37. Knockdown of p27 also reversed the inhibitory effect of CGRP on proliferation of PASMCs and expression of c-fos and c-myc, but not on ERK1/2 phosphorylation. These results suggest that CGRP inhibits hypoxia-induced proliferation of PASMCs via ERK1/2/p27/c-fos/c-myc pathway. Down-regulation of CGRP may contribute to remodeling of pulmonary arteries in hypoxia-induced pulmonary hypertension.

Estudo comparativo experimental da proteção miocárdica com soluções cristalóides para transplante cardíaco

There is a growing need to improve myocardial protection, which will lead to better performance of cardiac operations and reduce morbidity and mortality. Therefore, the objective of this study was to compare the efficacy of myocardial protection solution using both intracellular and extracellular crystalloid type regarding the performance of the electrical conduction system, left ventricular contractility and edema, after being subjected to ischemic arrest and reperfusion. Hearts isolated from male Wistar (n=32) rats were prepared using Langendorff method and randomly divided equally into four groups according the cardioprotective solutions used Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1 (STH-1) and Celsior (CEL). After stabilization with KHB at 37ºC, baseline values (control) were collected for heart rate (HR), left ventricle systolic pressure (LVSP), maximum first derivate of rise left ventricular pressure (+dP/dt), maximum first derivate of fall left ventricular pressure (-dP/dt) and coronary flow (CF). The hearts were then perfused at 10ºC for 5 min and kept for 2 h in static ischemia at 20ºC in each cardioprotective solution. Data evaluation was done using analysis of variance in completely randomized One-Way ANOVA and Tukey's test for multiple comparisons. The level of statistical significance chosen was P<0.05. HR was restored with all the solutions used. The evaluation of left ventricular contractility (LVSP, +dP/ dt and -dP/dt) showed that treatment with CEL solution was better compared to other solutions. When analyzing the CF, the HTK solution showed better protection against edema. Despite the cardioprotective crystalloid solutions studied are not fully able to suppress the deleterious effects of ischemia and reperfusion in the rat heart, the CEL solution had significantly higher results followed by HTK>KHB>STH-1.

Conflicting physiological and genomic cardiopulmonary effects of recruitment maneuvers in murine acute lung injury.

Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8 μl/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung mechanics during TI ventilation significantly deteriorated, as assessed by forced oscillation technique and pressure-volume curves. DI mitigated the TI-induced alterations in lung mechanics, but induced a significant rise in right ventricle systolic pressures and pulmonary vascular resistances, especially in LPS-challenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung inflammatory transcriptome, with prominent dysregulation of a gene cluster involving vascular processes, as well as increases in cytokine concentrations in bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right ventricular tissue expression profiles also identified inflammatory signatures, as well as apoptosis and membrane organization ontologies, as potential elements in the response to acute pressure overload. Our results, although confirming the improvement in lung mechanics offered by DI, highlight a detrimental impact in sustaining inflammatory response and exacerbating lung vascular dysfunction, events contributing to increases in right ventricle afterload. These novel insights should be integrated into the clinical assessment of the risk/benefit of recruitment maneuver strategies.

Effect of short- and long-term strength exercise on cardiac oxidative stress and performance in rat

Increase in heart metabolism during severe exercise facilitates production of ROS and result in oxidative stress. Due to shortage of information, the effect of chronic strength exercise on oxidative stress and contractile function of the heart was assessed to explore the threshold for oxidative stress in this kind of exercise training. Male Wistar rats (80) were divided into two test groups exercised 1 and 3 months and two control groups without exercise. Strength exercise was carried by wearing a Canvas Jacket with weights and forced rats to lift the weights. Rats were exercised at 70% of maximum lifted weight 6 days/week, four times/day, and 12 repetitions each time. Finally, the hearts of ten rats/group were homogenized and MDA, SOD, GPX, and catalase (CAT) were determined by ELISA method. In other ten rats/group, left ventricle systolic and end diastolic pressures (LVSP and LVEDP) and contractility indices (LVDP and +dp/dt max) and relaxation velocity (-dp/dt max) were recorded. The coronary outflow was collected. Short- and long-term strength exercise increased heart weight and heart/BW ratio (P < 0.05). In the 3-month exercise group, basal heart rate decreased (P < 0.05). LVEDP did not change but LVDP, +dp/dt max, -dp/dt max, and coronary flow significantly increased in both exercise groups (P < 0.05). None of MDA or SOD, GPX, and CAT significantly changed. The results showed that sub-maximal chronic strength exercise improves heart efficiency without increase in oxidative stress index or decrease in antioxidant defense capacity. These imply that long-time strength exercise up to this intensity is safe for cardiac health.

The Usefulness of D-Dimer, BNP, Right Ventricle Systolic Pressure (RVSP) as Predictor of the Severity of Pulmonary Thromboembolism

PURPOSE: D-dimer is an indicator with high sensitivity and negative predictive value to diagnose pulmonary embolism (PE). In recent years, several studies have shown that usefulness of D-dimer and brain natriuretic peptide (BNP) as predictors of severe PE and/or PE related mortality. Those studies have described the right ventricle dysfunction associated with PE by echocardiography. The aim of this study was to evaluate the usefulness of D-dimer, BNP and right ventricle systolic pressure (RVSP) as predictors of severity in patients with PE and to find proper cut off value of them.

Radiofrequency ablation of cardiac nerve attenuates Bezold–Jarisch reflex in canine

BackgroundThe Bezold–Jarisch reflex (BJR) is one of the main causes for vasovagal syncope (VVS). Blocking the efferent pathways of the vagus ganglia in the heart may attenuate the BJR.ObjectiveTo observe...

Reactivity of pulmonary circulation and right ventricle function to inhaled nitric oxide in systemic sclerosis patients.

Systemic sclerosis (SSc) is complicated by pulmonary hypertension and right ventricle (RV) failure in approximately 10% of the patients. Factors influencing the reactivity of pulmonary circulation to vasodilators are not established, while the examination of vasoreactivity is important in determining the treatment, because systemic administration of oral vasodilators can induce severe adverse events in nonresponders. The mechanism of RV failure in SSc is unclear and may result either from increased RV afterload or intrinsic myocardial disease. The aim of the study was to assess the reactivity of pulmonary circulation to inhaled nitric oxide (iNO) and to evaluate its influence on RV function in SSc patients with elevated right ventricle systolic pressure (RVSP). In 60 SSc patients aged 24–73 (58 females, two males; 33 patients with limited SSc and 27 with diffuse SSc), echocardiographic examination with tissue Doppler echocardiography (TDE) was performed. RV function was measured by systolic (S) and early diastolic (E) velocity of tricuspid annulus by TDE. In patients with RVSP >45 mmHg, the reactivity of pulmonary circulation was assessed by iNO test. High-resolution computerized tomography (HRCT) was performed to assess the extent of pulmonary fibrosis. Of 14 SSc subjects with elevated RVSP (13 females, one male; RVSP 47–62 mmHg), positive reaction to iNO was observed in five (RVSP decreased from 51.6 ± 3.7 to 32.24 ± 2.3 mmHg); nine patients were not reactive (RVSP 53.5 ± 5.7 mmHg before iNO vs. 49.6 ± 6.7 mmHg). RV systolic function was decreased in patients with elevated RVSP as compared to the patients with normal pulmonary pressure (S velocity 13.2 ± 1.3 vs. 14.4 ± 1.6 cm/s, respectively, p < 0.05). Significant increase of RV systolic function during iNO test was found in reactive patients only (S velocity before iNO 12.8 ± 1.2 cm/s, during iNO 14.5 ± 1.5 cm/s, p < 0.01). RVSP decrease strongly correlated with S velocity increase (r = 0.95, p < 0.0001). Response to iNO was found only in limited form of SSc; diffuse SSc patients showed no response. Pulmonary fibrosis on HRCT was more frequent in subjects nonreactive to iNO (67% of patients) than in the reactive group (40% of patients). The reactivity of pulmonary circulation to iNO in SSc patients with elevated RVSP was found predominantly in limited form of the disease. Pulmonary fibrosis typical for diffuse SSc was more frequent in nonreactive subjects. Elevated pulmonary pressure plays an important role in RV systolic dysfunction. Pulmonary pressure decrease during iNO test leads to the improvement of RV systolic function. Therapy for right-heart failure in reactive SSc patients should be directed, if possible, at the decrease in pulmonary resistance.

The combined transduction of copper, zinc-superoxide dismutase and catalase mediated by cell-penetrating peptide, PEP-1, to protect myocardium from ischemia-reperfusion injury

BackgroundOur previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced injury in rats. The aim of this study is to explore whether combined use of PEP-1-SOD1 and PEP-1-CAT enhances their protective effects.MethodsSOD1, PEP-1-SOD1, CAT or PEP-1-CAT fusion proteins were prepared and purified by genetic engineering. In vitro and in vivo effects of these proteins on cell apoptosis and the protection of myocardium after ischemia-reperfusion injury were measured. Embryo cardiac myocyte H9c2 cells were used for the in vitro studies. In vitro cellular injury was determined by the expression of lactate dehydrogenase (LDH). Cell apoptosis was quantitatively assessed with Annexin V and PI double staining by Flow cytometry. In vivo, rat left anterior descending coronary artery (LAD) was ligated for one hour followed by two hours of reperfusion. Hemodynamics was then measured. Myocardial infarct size was evaluated by TTC staining. Serum levels of myocardial markers, creatine kinase-MB (CK-MB) and cTnT were quantified by ELISA. Bcl-2 and Bax expression in left ventricle myocardium were analyzed by western blot.ResultsIn vitro, PEP-1-SOD1 or PEP-1-CAT inhibited LDH release and apoptosis rate of H9c2 cells. Combined transduction of PEP-1-SOD1 and PEP-1-CAT, however, further reduced the LDH level and apoptosis rate. In vivo, combined usage of PEP-1-SOD1 and PEP-1-CAT produced a greater effect than individual proteins on the reduction of CK-MB, cTnT, apoptosis rate, lipoxidation end product malondialdehyde, and the infarct size of myocardium. Functionally, the combination of these two proteins further increased left ventricle systolic pressure, but decreased left ventricle end-diastolic pressure.ConclusionThis study provided a basis for the treatment or prevention of myocardial ischemia-reperfusion injury with the combined usage of PEP-1-SOD1 and PEP-1-CAT fusion proteins.