Systolic Fractional Shortening Research Articles

Characterizing left ventricular diastolic function, exercise capacity and the adrenal cortex after yoyo diet-induced weight-cycling in mice with or without ovariectomy-induced post-menopausal condition

Studies report that only ∼20% of overweight people achieve sustainable weight loss with the risk to incur weight cycling. The over-shoot theory relates to an increased risk to develop metabolic syndrome (metS) and associated cardiovascular dysfunctions with successive phases of weight gain. In women, the prevalence of metS and heart failure with preserved ejection fraction (HFpEF) increases after menopause. To characterize the cardiac and adrenal consequences of yoyo-dieting in female mice with or without ovariectomy-induced post-menopausal condition. After ovariectomy (OVX) or not, mice were subjected to 3 cycles of a 60% high fat diet (HFD, 4-week duration) followed by a standard diet (SD) (increasing duration of 4, 6 and 10 weeks). Non-OVX control mice (CTL) were fed a SD. To assess the development of HFpEF, left ventricular (LV) function was characterized by ultrasound and invasive hemodynamics. Exercise capacity was evaluated on a treadmill. The morphology of the adrenal gland was described using HES staining, Sirius Red and immunofluorescence. Adrenal function and the vascular network were assessed using RT-qPCR to quantify mRNA expression for genes involved respectively in steroidogenesis and angiogenesis. At the end of the protocol, Yoyo mice had incomplete weight recovery and an insulin tolerance test indicated decreased sensitivity to the hormone. Moreover, there was an increase in LV-end-diastolic-pressure-volume-relation in OVX-Yoyo mice compared to CTL mice, indicating decreased compliance. In addition, the absence of difference in systolic fractional shortening (i.e., ejection fraction) and a lower exercise capacity in OVX-Yoyo mice compared to CTL demonstrated HFpEF. These OVX-Yoyo mice had major disorganization and remodeling in the adrenal gland with the apparition of dysplasia and fibrosis throughout the cortex. The vascular architecture was also affected, with lower expression of Vegf-a. Despite higher adrenal weight, there was no difference in cell proliferation. Whereas CYP11B2 expression, coding for the aldosterone synthase was not affected, the mRNA expression of CYP11B1, involved in glucocorticoids biosynthesis, was lower in OVX-Yoyo mice. Female mice in post-menopausal condition and subjected to yoyo-dieting showed an increased risk of developing HFpEF as well as major morphological and functional differences in the adrenal cortex.

Short- and long-term treatment with mineralocorticoid receptor antagonist improved heart failure with preserved ejection fraction in obese female mice with or without ovariectomy-induced post-menopausal condition

Obesity and metabolic syndrome are major risks for the development of heart failure with preserved ejection fraction (HFpEF), especially in women after menopause. Although mineralocorticoid receptor antagonists (MRAs) improve outcomes of HF with reduced EF, their beneficial effects on HFpEF remain to be established. We aimed to characterize the potential beneficial effects of an MRA treatment on HFpEF related to obesity in post-menopausal condition or not. After 12 weeks of a high fat diet (HFD), B6D2 female mice underwent an ovariectomy (OVX) followed by an MRA treatment (daily gavage) for a short- or long-term (1 or 12 weeks). The metabolic profile of the mice was analyzed by glucose and insulin tolerance tests. Echocardiography and hemodynamics measurements were performed to evaluate the left ventricular (LV) function. LV coronary perfusion and reserve were measured by MRI, and exercise capacity was evaluated on a treadmill. LV and adrenal gland remodeling were explored by histology and immunohistochemistry. After 12 weeks of HFD, the LV systolic fractional shortening, stroke volume and cardiac output in obese mice were not different to control mice. However, impairment of the LV diastolic compliance was significantly improved either by a short- or long-term MRA treatment (LV-End-Diastolic-Pressure-Volume-Relation, mmHG/RVU: CTL 1.00 ± 0.27, HFD 3.29 ± 0.56, HFD + OVX 7.33 ± 0.35; P < 0.01 vs. CTL; HFD + MRAshort 1.13 ± 0.35, HFD + OVX + MRAshort 0.95 ± 0.51; P < 0.01 vs. untreated). Furthermore, the long-term MRA treatment ameliorated glucose and insulin tolerance tests and reduced LV interstitial fibrosis (Fibrosis, %: CTL 7.03 ± 0.41, HFD 8.82 ± 0.36, HFD + OVX 9.80 ± 0.58; P < 0.01 vs. CTL; HFD + MRA 6.45 ± 0.51, HFD + OVX + MRA 8.26 ± 0.28; P < 0.01 vs. untreated). Moreover, in HFD + OVX mice, the long-term MRA treatment increased the coronary perfusion reserve as well as the running distance during the treadmill stress test. Obesity and post-menopausal condition affected adrenal gland organization with capsule thinning in all obese mice, spindles cortical extensions in the HFD group, cortical dysplasia and disorganized vascular network in the HFD + OVX group. Overall, our data demonstrate that both short- and long-term MRA treatment improved diastolic dysfunction in pre- and post-menopausal obese female mice with HFpEF.

Using DeepLabCut as a Real-Time and Markerless Tool for Cardiac Physiology Assessment in Zebrafish.

Simple SummaryWith the advancement of existing technology, artificial intelligence is widely applied in various fields of research, including cardiovascular studies. In this study, we explored the feasibility of conducting a markerless cardiac physiology assessment in zebrafish embryos by using DeepLabCut (DLC), a deep learning tool for motion analysis. Several cardiac parameters, such as heart rate, diastolic–systolic volumes (EDV/ESV), stroke volume, cardiac output, shortening fraction, and ejection fraction were obtained by the DLC-trained model and then compared to the previous published methods, Time Series Analysis and Kymograph. This new method has several advantages, having full automation, precise detection, and real-time labelling. This network was also trained to analyze zebrafish with cardiovascular defects (pericardial edema) induced by chemical treatments with ethanol and ponatinib. It was revealed that the heart rate, EDV/ESV, stroke volume, and cardiac output from both the ethanol and ponatinib groups displayed significant reductions compared with the control. Hopefully, this trained DLC network can contribute to a better understanding and investigation of the existing cardiovascular system and abnormalities.DeepLabCut (DLC) is a deep learning-based tool initially invented for markerless pose estimation in mammals. In this study, we explored the possibility of adopting this tool for conducting markerless cardiac physiology assessment in an important aquatic toxicology model of zebrafish (Danio rerio). Initially, high-definition videography was applied to capture heartbeat information at a frame rate of 30 frames per second (fps). Next, 20 videos from different individuals were used to perform convolutional neural network training by labeling the heart chamber (ventricle) with eight landmarks. Using Residual Network (ResNet) 152, a neural network with 152 convolutional neural network layers with 500,000 iterations, we successfully obtained a trained model that can track the heart chamber in a real-time manner. Later, we validated DLC performance with the previously published ImageJ Time Series Analysis (TSA) and Kymograph (KYM) methods. We also evaluated DLC performance by challenging experimental animals with ethanol and ponatinib to induce cardiac abnormality and heartbeat irregularity. The results showed that DLC is more accurate than the TSA method in several parameters tested. The DLC-trained model also detected the ventricle of zebrafish embryos even in the occurrence of heart abnormalities, such as pericardial edema. We believe that this tool is beneficial for research studies, especially for cardiac physiology assessment in zebrafish embryos.

Ononin alleviates endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity by activating SIRT3

Doxorubicin (DOX) is a potent anthracycline antineoplastic drug. However, its dose-dependent cardiotoxicity limits its clinical application. Ononin is a natural isoflavone glycoside that is crucial in modulating apoptosis-related signaling pathways. In this study, we assessed the possible cardioprotective effects of ononin in DOX-induced cardiotoxicity and elucidated the underlying molecular mechanisms. In vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats, respectively. First, DOX was injected into the tail veins of Wistar rats to induce cardiomyopathy. Next, rats in the DOX + Ononin30 and DOX + Ononin60 groups were intragastrically administered ononin two weeks before DOX treatment. H9C2 cells were treated with vehicle or DOX with or without ononin. Next, 3-TYP was used to determine the relationship between endoplasmic reticulum (ER) stress and sirtuin 3 (SIRT3) expression. Ononin treatment ameliorated DOX-induced myocardial injury as determined by echocardiography. Furthermore, ononin partially restored DOX-induced cardiac dysfunction; the left ventricular ejection fraction (LVEF) and left ventricular systolic fractional shortening (LVFS) increased after pre-treatment with ononin. Further, ononin suppressed DOX-induced ER stress and apoptosis in rat cardiomyocytes and H9C2 cells. The Bax/Bcl-2 ratio and 78-kD glucose-regulated protein (GRP78) and CCAAT enhancer-binding protein (CHOP) expression levels were higher in the DOX-treated group than in the control group but ononin treatment improved these parameters. These effects are associated with SIRT3 activity. Moreover, 3-TYP blocked the ononin-mediated protective effects. Hence, ononin positively affected DOX-induced cardiotoxicity by inhibiting ER stress and apoptosis, possibly mediated by stimulation of the SIRT3 pathway.

Pulmonary-cardiac hemodynamics in patients with major surgical interventions on the lungs according to the data of doppler echocardiography

ntroduction. The choice of the optimal scope of inter-ventions for major operations on the lungs, including re-constructive plastic surgery, combined pneumonectomy, depends, among other things, on the degree of decrease in the functional reserves of the cardiovascular system. The study aims the evaluation of the functional state of the right ventricle (RV) of the heart, the level of secondary pulmonary hypertension before and after major surgical interventions on the lungs. Materials and methods. The study included 32 patients aged 41 to 74 years (29 men and 3 women) who underwent pneumonectomy with circular resection of the tracheal bifurcation and various types of combined pneumonectomy. The control group consisted of 37 practically healthy individuals aged 23 to 59 years (17 men and 20 women). Doppler echocardio-graphy was used to study the parameters of the pulmo-nary circulation (before and 3–5 days after the operation). Results. As possible alternative indicators characterizing the state of the pumping function of theRV, it is possible to recommend the use of the systolic shortening fraction (SSF) of theRV, the amplitude of movement of the tricuspid valve ring and the end-diastolic size of theRV. Decreased SSF of the RV below 0,2, amplitude of movement of the tricuspid valve ring less than 1,6 cm, and dilatation of the RV over 3.5 cm in diastole may indicate a pronounced de-crease in the contractile function of the RV. Conclusion.In patients with initially impaired hemodynamics, func-tional changes after surgical interventions were more pronounced. The boundaries of the shift of the main ultra-sound parameters of the right ventricular function were determined to form a group of increased prognostic risk

Echocardiographic changes in patients with a cylinder mitral valve replacement: Preliminary analysis.

Cylinder mitral valve construct (cMVC) is new technique for replacing the mitral valve compared to more traditional mitral valve replacement (MVR) procedures. Goal of this study was to describe echocardiographic changes over time in patients undergoing a cMVC. Secondary goal was to compare echocardiographic changes in patients that underwent a cMVC to a group of patients that underwent a MVR. Retrospective analysis of patients undergoing a cMVC was performed. Demographics, discharge echocardiogram, and recent echocardiogram vales were evaluated. Age matched patients undergoing a MVR were assessed. Discharge and recent echocardiographic parameters were compared within the cMVC group. cMVC and MVR values were compared between groups. Five cMVC patients were studied. Age at surgery for the cMVC was 4.3±4.2 years (median 2.2, .8-10.3 years). Time interval from hospital discharge echocardiogram to the most recent echocardiogram was 1.2±.7 years (median 1.0, .6-2.0 years). Mean mitral valve gradient significantly increased over time (3.6±3.0mm Hg vs 7.6±2.9mm Hg). There were significant improvements in left ventricular diameters, systolic sphericity index, shortening fraction, and ejection fraction over time. There were no significant differences in demographics, discharge echocardiogram values, and follow up echocardiogram values between the cMVC and MVR groups. In conclusion, echocardiographic indices of left ventricular function improved over time in patients undergoing cMVC. In addition, there were no significant differences between cMVC and MVR patients in echocardiographic values. Studies with a larger patient sample with longer follow up are needed to determine if cMVC continues to have comparable echocardiographic results to MVR.

Quantitative characterization of left ventricular function during pulseless electrical activity using echocardiography during out-of-hospital cardiac arrest

BackgroundSeveral prospective studies have demonstrated that the echocardiographic detection of any myocardial activity during PEA is strongly associated with higher rates of return of spontaneous circulation (ROSC). We hypothesized that PEA represents a spectrum of disease in which not only the presence of myocardial activity, but more specifically that the degree of left ventricular (LV) function would be a predictor of outcomes. The purpose of this study was to retrospectively assess the association between LV function and outcomes in patients with OHCA. Materials and methodsUsing prospectively obtained data from an observational cohort of patients receiving focused echocardiography during cardiopulmonary resuscitation (CPR) in the Emergency Department (ED) setting, we analyzed 312 consecutive subjects with available echocardiography images with initial rhythm of PEA. We used left ventricular systolic fractional shortening (LVFS), a unidimensional echocardiographic parameter to perform the quantification of LV function during PEA. Regression analyses were performed independently to evaluate for relationships between LVFS and a primary outcome of ROSC and secondary outcome of survival to hospital admission. We analyzed LVFS both as a continuous variable and as a categorial variable using the quartiles and the median to perform multiple different comparisons and to illustrate the relationship of LVFS and outcomes of interest. We performed survival analysis using Cox proportional hazards model to evaluate the hazard corresponding to length of resuscitation. ResultsWe found a positive association between LVFS and the primary outcome of ROSC (OR 1.04, 95%CI 1.01–1.08), but not with the secondary outcome of survival to hospital admission (OR 1.02, 95%CI 0.96–1.08). Given that the relationship was not linear and that we observed a threshold effect in the relationship between LVFS and outcomes, we performed an analysis using quartiles of LVFS. The predicted probability of ROSC was 75% for LVFS between 23.4–96% (fourth quartile) compared to 47% for LVFS between 0–4.7% (first quartile). The hazard of not achieving ROSC was significantly greater for subjects with LVFS below the median (13.1%) compared to the subgroup with LVFS greater than 13.1% (p < 0.05), with the separation of the survival curves occurring at approximately 40 min of resuscitation duration. ConclusionsLeft ventricular function measured by LVFS is positively correlated with higher probability of ROSC and may be associated with higher chances of survival in patients with PEA arrest.

Fetal Heart Function by Tricuspid Annular Plane Systolic Excursion and Ventricular Shortening Fraction Using STIC M-Mode: Reference Ranges and Validation.

Objective To determine the reference values for fetal tricuspid annular plane systolic excursion (f-TAPSE) and fetal ventricular shortening fraction (f-VSF) using spatiotemporal image correlation (STIC) with M-mode, and validate these curves in fetuses of pregnant women with preexisting diabetes mellitus (DM) and with intrauterine growth restriction (IUGR). Study Design Crosssectional study assessed 300 fetal cardiac volumes of normal pregnancies between 20 and 33 + 6 weeks of gestation. For the construction of the reference curves, we used a polynomial regression model adjusted with the coefficient of determination (R2). For the calculation of reproducibility, the concordance correlation coefficient (CCC) was used. Results f-TAPSE value correlated with gestational age (GA, R2 = 0.46), whereas fetal right ventricular shortening fraction (f-RVSF, R2 = 0.02) and fetal left ventricular shortening fraction (f-LVSF, R2 = 0.005) did not vary with GA. Fetuses of pregnant women with preexisting DM (30) had lower values of f-RVSF (p = 0.028), f-LVSF (p = 0.001), and f-TAPSE (p = 0.009) than normal fetuses. The f-TAPSE values were lower (p = 0.005) in IUGR group (17). The f-TASPSE values showed adequate reliability as well as good intra and interobserver concordance (CCC = 0.95 and 0.79, respectively). Conclusion The reference ranges for f-TAPSE, f-RVSF, and f-LVSF using the STIC M-mode were established and had good reproducibility for f-TAPSE measurements.

Cause analysis of young patients with chest pain and negative results of coronary angiography

Objective To reduce the incidence of sudden cardiac death in young individuals with chest pain suspected to be acute coronary syndrome (ACS) and negative results of angiography, and so explored the causes of it. Methods A total of 134 young patients with suspected ACS admitted in PLA general hospital from January 2014 to December 2014 , were checked by coronary angiography. Comparisons of gender, professions, BMI, biochemical variables including glycohemoglobin (HBA1c), triglyceride (TG), C-reactive protein (CRP), troponin T (cTnT), high-density lipoprotein (HDL), brain natriuretic diuresis peptide (BNP)) and cardiac function including interventricular septum thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume and left ventricular systolic volume, stroke volume, ejection fraction and shortening fraction of left ventricle, E value, A value, E/A value among coronary angiography negative group (n=64), coronary angiography positive group (n=70) and healthy subjects group (n=77) . Quantitative variables were presented as means ± standard deviations, categorical data were presented as absolute values and percentages compared using t-test. One-way ANOVA was used to analyze variance between groups. Results The causes of negative group were found to be coronary atherosclerosis (90.6%), cardiac neurosis (4.7%), cardiomyopathy (1.6%), cardiac syndrome X (1.6%), and other 3.2%. There were 81.1% male and 58.9% officer of civil service management and business service personnel in negative group. The young patients in negative group had higher levels of BMI (P=0.000), total cholesterol (TC) (P=0.000), hypersensitive C-reactive protein (CRP) (P=0.003), cardiac troponin T (cTnT) (P=0.009) and lower high density lipoprotein (HDL) (P=0.000) compared with healthy subjects group. There was no significant difference in level of brain natriuretic peptide (BNP) between negative group and healthy subjects group (P=0.128). There were higher levels of left ventricular ejection fraction (LVEF) (P=0.000) and fractional shortening (FS) (P=0.000), and lower left ventricular end systolic volume (P=0.006) in negative group compared with positive group. Conclusions Coronary atherosclerosis is the major cause of young patients with chest pain suspected acute coronary syndrome (ACS) and with negative results of coronary angiography. Male, high stress occupation, a sedentary job, obesity, hyperglycemia and dyslipidemia are risk factors. Early diagnosis and prevention strategy are mandatory in these specific young individuals. Key words: Young people; Acute coronary syndrome; Sudden cardiac death; Chest pain; Causes; Coronary angiography negative; Biochemical indicators; Gender; Profession; Heart function

Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.

This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. When compared with nondiabetic LDLr(-/-)/ApoB(100/100), diabetic LDLr(-/-)/ApoB(100/100)/IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr(-/-)/ApoB(100/100)/IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr(-/-)/ApoB(100/100) mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr(-/-)/ApoB(100/100)/IGF-II mice when compared with LDLr(-/-)/ApoB(100/100). Importantly, we found that peak aortic jet velocity was significantly increased in LDLr(-/-)/ApoB(100/100)/IGF-II mice versus LDLr(-/-)/ApoB(100/100) animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes (anp, bnp, b-mhc) in myocardial tissues and of osteogenic genes (spp1, bglap, runx2) in aortic tissues of diabetic mice. We have established the diabetes mellitus -prone LDLr(-/-)/ApoB(100/100)/IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis.

Comparison of right ventricular measurements and SFRV in fetuses with and without tricuspid regurgitation at 11+0 and 13+6 weeks’ gestation

Objectives: To compare right ventricular dimensions and systolic shortening fraction of the right ventricle (SFRV) in fetuses with tricuspid regurgitation (TR [+]) to those without tricuspid regurgitation (TR [−]).Methods: Unselected patients presenting for first trimester screening between 11 + 0 and 13 + 6 weeks’ gestation were examined for the presence or absence of fetal tricuspid regurgitation using a standard approach. Only euploid fetuses without structural anomalies were included in the study. The heart was examined with the aid of M-mode using a previously described method. The right ventricular diastolic diameter (RVDD) and right ventricular systolic diameter (RVSD) were measured on stored M-mode images and the SFRV was calculated using the following formula [(RVDD−RVSD)/RVDD] × 100.Results: A total of 69 fetuses (n = 44 (TR [−]); n = 25 (TR [+])) were examined. The two groups were similar in maternal age, gestational age and nuchal translucency (NT) measurements. The SFRV was noted not to change with gestational age and there was no statistical difference between the two groups. Both the RVDD and the RVSD increased with gestational age. The calculated delta RVDD was statistically larger in the TR [+] group (mean: 0.29, CI 95%: 0.054–0.532) than the TR [−] group (mean: 0.013, CI 95%: −0.128 to 0.154) (p < 0.05). This was not true for the delta RVSD: TR [+] (mean: 0.17, CI 95%: 0.015–0.325) versus TR [−] group (mean: 0.035, CI 95%: −0.061 to 0.131). However, there was a trend towards larger RVSD in the TR [+] group (p = 0.13).Conclusions: The presence of TR appears to be associated with an increased RVDD in normal fetuses between 11 + 0 and 13 + 6 weeks’ gestation.

Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice.

BackgroundDilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR‐669a downregulation has been linked to the severe DCM progression displayed by Sgcb‐null dystrophic mice. However, the impact of long‐term overexpression of miR‐669a on muscle structure and functionality of the dystrophic heart is yet unknown.Methods and ResultsHere, we demonstrate that intraventricular delivery of adeno‐associated viral (AAV) vectors induces long‐term (18 months) miR‐669a overexpression and improves survival of Sgcb‐null mice. Treated hearts display significant decrease in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR‐669a treatment increases sarcomere organization, reduces ventricular atrial natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM markers. Furthermore, long‐term miR‐669a overexpression significantly reduces adverse remodeling and enhances systolic fractional shortening of the left ventricle in treated dystrophic mice, without significant detrimental consequences on skeletal muscle wastage.ConclusionsOur findings provide the first evidence of long‐term beneficial impact of AAV‐mediated miRNA therapy in a transgenic model of severe, chronic MD‐associated DCM.

231: At early phase of endotoxemic shock the increased β-adrenergic contractility is dependent of the endothelial β1-adrenoceptor

Cardiovascular alterations in the septic shock include an hypotension associated with a cardiomyopathy. The sympathetic regulation of the cardio-vascular system is impaired during the shock and associated with an altered endothelial function. However, involved cellular mechanisms are not clear. The aims of this project were to determine the role of the three β-adrenoceptor subtypes, β 1 , β 2 and β 3 -AR in the cardiac dysfunction in endotoxemic rats. Rats (12w) received either endotoxin (LPS, 5mg. kg -1 ) or saline i.v. (C). 3h later, cardiac parameters were studied in vivo by echocardiography. Selective β-AR responses were studied on papillary muscle contractility with or without a functional endothelium. Endothelium damage was realized with 3s Triton X-100 at 0.5%. In vivo , LPS rats presented altered systolic (shortening fraction -21±4% vs C p<0.05) and diastolic (E wave -47±4% vs C p<0.05) functions. In papillary muscle, isoproterenol (non selectif βAR agonist) induced contractility was increased in LPS (+105±21% vs C; p<0.05). This increase did not result from β 3 -AR and β 2 -AR because there expressions were respectively decreased by 20±4%; (p<0.05 vs C) and 47±7% (p<0.05 vs C) in LPS and correlated to a maintained β 3 -AR-induced contractility and a decreased β 2 -AR (-38±8% vs C; p<0.05). The β 2 -AR-induced contractility was not modified in LPS muscle without endothelium whereas it was reduced in C muscle without endothelium (79±6% vs C; p<0.05). Conversely, albeit β 1 -AR expression was decreased (-66±5% vs C; p<0.05), β 1 -AR response was increased in papillary muscles (+94±16% vs C; p<0.05) from LPS rats. Surprisingly, the disrupted endothelium abolished this increase. Our results demonstrate, for the first time, an increased β 1 -AR contractility, on papillary muscle form LPS rats, dependent of the functional endothelium. This suggests that β 1 -AR could be involved in the persistent tachycardia observed in the shock leading to propose β 1 -AR blockers in this disease.

Cardiac evaluation after experimental intoxication by Amorimia rigida (Malpighiaceae) extracts in rabbits

Clinical and laboratory changes were evaluated in rabbits after intoxication by Amorimia rigida, a plant that causes sudden death. Nine New Zealand male rabbits, averaging 3.54 kg, were categorized into three groups (n = 3) and received, for eight consecutive days, the equivalent of 30 g/kg dry matter of A. rigida water-soluble (SG) and water-insoluble (IG) extracts via nasoesophageal route. The control group received water. There were no alterations in creatine kinase enzyme (CK), CK myocardial fraction (CKMB) or troponine I (cTnI). None of the animals had clinical or electrocardiographic (conventional and Holter) alterations. There were progressive decreases in the left ventricular ejection fraction and systolic fractional shortening. Doppler echocardiography alterations suggested a systolic dysfunction in the SG and IG groups and diastolic dysfunction in IG group. It was concluded that the soluble and insoluble extracts of A. rigida cause deficit of cardiac function.

Renal Resistive Index in 55 Dogs with Degenerative Mitral Valve Disease

Azotemia occurs frequently in dogs with degenerative mitral valve disease (DMVD). It could indicate changes in renal hemodynamics. To assess the renal resistive index (RI) in dogs with DMVD, and the statistical link between heart failure class, azotemia, echo-Doppler parameters, several plasma variables, and RI. Fifty-five dogs with naturally occurring DVMD were used (ISACHC class 1 [n = 28], 2 [n = 19], and 3 [n = 8]). Observational, blinded study, performed under standardized conditions. Physical examination, renal ultrasonography, and echo-Doppler examinations were performed in awake dogs. The RI of the renal, interlobar, and arcuate arteries were measured. Plasma creatinine, urea, and N-terminal pro-B-type natriuretic peptide concentrations (NT-proBNP) were determined. Statistical links between variables and RI were tested by means of a general linear model. Although the RI of renal and arcuate arteries were unaffected by ISACHC class, the left interlobar RI increased (P < .001) from 0.62 ± 0.05 (mean ± SD) in class 1 to 0.76 ± 0.08 in class 3. It was also higher (P < .001) in azotemic (0.74 ± 0.08) than in non-azotemic (0.62 ± 0.05) dogs. Similar findings were observed for right interlobar RI. Univariate analysis showed a positive statistical link between NT-proBNP (P = .002), urea (P < .001), creatinine (P = .002), urea-to-creatinine ratio (P < .001), left atrium-to-aorta ratio (P < .001), regurgitation fraction (P < .001), systolic pulmonary arterial pressure (P < .001), shortening fraction (P = .035), and RI. In dogs with DMVD, interlobar RI increases with heart failure severity and azotemia but a cause and effect relationship remains to be established.

Association Between Left Atrial Size and Measures of Adiposity Among Normal Adolescent Boys

Obesity (OB) in adults is associated with insulin resistance, hypertension, and left atrial (LA) enlargement. This study aimed to determine the association between LA size and (1) different components of the metabolic syndrome (body mass index [BMI], waist circumference [WC], insulin levels, lipid levels, and blood pressure), and (2) left ventricular (LV) diameters and diastolic function. Data were collected cross-sectionally from 142 healthy adolescent boys age 16.8 ± 2.0 years in 2009. Measurements of BMI, WC, blood pressure, lipid profile, and insulin were performed. Mode M, two-dimensional Doppler echocardiography was performed. Measurements of LA area, LV end diastolic diameter (EDD), end systolic diameter (ESD), posterior wall, interventricular septum (IVS), and shortening fraction were performed. Tisular Doppler of the diastolic mitral annular E wave (DTE) and A wave (DTA) and the ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity (E/e') were recorded. The study group included 38 OB boys (26.8%) and 32 overweight boys (22.5%). Significant univariate association was found between LA area and BMI (r = 0.61), WC (r = 0.56), systolic blood pressure (r = 0.21), insulinemia (r = 0.28), high-density lipoprotein-cholesterol (HDL-C) (r = -0.24), triglycerides (r = 0.20), EDD (r = 0.25), LV posterior wall (r = 0.25), IVS (r = 0.25), DTE (r = 0.27), DTA (r = 0.30), and E/e' (r = -0.28). Multiple linear regression analysis showed that LA area was associated with BMI (B = 0.61; R (2) = 0.47) adjusted for confounding variables. In adolescents, BMI and WC were significantly associated with LA, suggesting that OB could be associated with LA enlargement as early as adolescence.

Papillary Muscle Function Does Not Predict Mitral Regurgitation in Patients with Normal Left Ventricular Systolic Function: A Transesophageal Echocardiographic Study

Objective: To evaluate LV papillary muscles (PM) function using transesophageal echocardiography (TEE), and to determine the relationship between PM function and mitral regurgitation in patients with normal left ventricular sys-tolic function. Design: TEE examinations were prospectively performed. End diastolic and end systolic PM lengths were obtained from the transgastric long axis views and fractional systolic shortening (FS) was calculated. LV ejection fraction was determined using modified Simpson rule and mitral regurgitation was determined using regurgitant jet area by color flow. Setting: Tertiary Center. Patients: 85 consecutive adult patients (51 with mitral regurgitation and 34 without) with normal LV chamber dimensions and LV systolic function, meeting enrollment criteria. Results: The % FS in patients with mitral regurgitation was 21.7 ± 3.6% for anterior PM (APM) and 18.7 ± 4.6% for posterior PM (PPM). In those without mitral regurgitation, the values were as follows; 22.6 ± 5.4% (APM) and 19.5 ± 3.8% (PPM). In a subgroup of patients with severe mitral regurgitation (n = 23), the values for PM FS were 20.3 ± 6.8 (APM) and 18.4 ± 6.9 % (PPM). There was no statistically significant difference in PM fractional shortening between the groups. Anterior papillary muscle length was longer in those patients with mitral regurgitation compared to those without [(End-diastolic length (cm): 3.38 ± 0.61 v 2.88 ± 0.47(p: 0.008) and end-systolic length of 2.46 ± 0.51 v 2.17 ± 0.33 (p: 0.04)]. These differences are more pronounced in those with severe mitral regurgitation (p: 0.002 and 0.004 for EDL and ESL respectively. Conclusion: In patients with normal LVEF, PM contraction is similar in those with and without MR. In patients with MR however, anterior PM length (ED & ES) is significantly increased. Our data suggests that in patients with normal LVEF, PM dysfunction appears to play no significant role in the causation of MR. Anterior papillary muscle length however, appears to be a major determinant of mitral regurgitation in such patients.

Avaliações clínico-patológicas e laboratoriais da intoxicação experimental por monofluoroacetato de sódio em ovinos

O objetivo deste trabalho foi verificar se a administração de doses únicas e de frações diárias da dose letal de monofluoroacetato de sódio (MF) a ovinos induzem a clássica degeneração hidrópico-vacuolar (DHV) dos túbulos uriníferos contornados distais observada no rim de bovinos intoxicados por plantas brasileiras que causam "morte súbita" (PBCMS). MF foi administrado, por via oral, em doses únicas de 0,5 e 1,0mg/kg, cada dose para dois ovinos, e em doses subletais repetidas diariamente de 0,1mg/kg/dia, por quatro dias, e 0,2mg/kg/dia por seis dias, cada dose para um ovino. Todos os ovinos que receberam MF morreram, exceto um que recebeu 0,5mg/kg e não mostrou sintomas. A evolução da intoxicação variou de 3min a 33h5min. Clinicamente os animais apresentaram taquicardia, respiração abdominal, tremores musculares, ligeira perda de equilíbrio, por vezes cambaleavam, deitavam e apoiavam a cabeça no flanco. Na fase final, os ovinos caíam em decúbito lateral, esticavam os membros, faziam movimentos de pedalagem, apresentavam opistótono e morriam. O exame ecocardiográfico evidenciou dilatação cardíaca e redução da fração de encurtamento sistólico. A análise dos níveis séricos de uréia e creatinina revelou moderada a acentuada azotemia. MF provocou "morte súbita" em todos os ovinos que mostraram sintomas. À necropsia verificaram-se aurículas e veias jugulares, cavas, ázigos e pulmonares moderadamente ingurgitadas e, em alguns animais, edema pulmonar. O exame histopatológico revelou, em todos os ovinos, leve a acentuada DHV das células epiteliais dos túbulos contornados distais, associada à picnose nuclear. Adicionalmente, verificaram-se discreta vacuolização e, por vezes, necrose de coagulação de hepatócitos. Não encontramos referências a esse tipo peculiar de lesão, exceto das descrições sobre lesões renais associadas à ingestão de PBCMS e de recentes estudos em bovinos intoxicados com MF. Este trabalho demonstra, em ovinos, que tanto doses letais únicas quanto subdoses diárias de MF induzem a DHV dos túbulos uriníferos contornados distais associada à picnose nuclear.

Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation

Our objective was to address the balance of inducible nitric oxide (NO) synthase (iNOS) and arginase and their contribution to contractile dysfunction in heart failure (HF). Excessive NO formation is thought to contribute to contractile dysfunction; in macrophages, increased iNOS expression is associated with increased arginase expression, which competes with iNOS for arginine. With substrate limitation, iNOS may become uncoupled and produce reactive oxygen species (ROS). In rabbits, HF was induced by left ventricular (LV) pacing (400 beats/min) for 3 wk. iNOS mRNA [quantitative real-time PCR (qRT-PCR)] and protein expression (confocal microscopy) were detected, and arginase II expression was quantified with Western blot; serum arginine and myocardial nitrite and nitrate concentrations were determined by chemiluminescence, and protein S-nitrosylation with Western blot. Superoxide anions were quantified with dihydroethidine staining. HF rabbits had increased LV end-diastolic diameter [20.0 + or - 0.5 (SE) vs. 17.2 + or - 0.3 mm in sham] and decreased systolic fractional shortening (11.1 + or - 1.4 vs. 30.6 + or - 0.7% in sham; both P < 0.05). Myocardial iNOS mRNA and protein expression were increased, however, not associated with increased myocardial nitrite or nitrate concentrations or protein S-nitrosylation. The serum arginine concentration was decreased (124.3 + or - 5.6 vs. 155.4 + or - 12.0 micromol/l in sham; P < 0.05) at a time when cardiac arginase II expression was increased (0.06 + or - 0.01 vs. 0.02 + or - 0.01 arbitrary units in sham; P < 0.05). Inhibition of iNOS with 1400W attenuated superoxide anion formation and contractile dysfunction in failing hearts. Concomitant increases in iNOS and arginase expression result in unchanged NO species and protein S-nitrosylation; with substrate limitation, uncoupled iNOS produces superoxide anions and contributes to contractile dysfunction.

Effect of pregnancy on clinical status and ventricular function in women with heart disease

Background Pregnant women with heart disease (HD) are at an increased risk for maternal and neonatal adverse events. However, the effect of pregnancy on clinical status and ventricular function in women with HD has not been examined in a controlled study. Methods and results Ninety-three women with HD were studied longitudinally. Of these, fifty-three underwent clinical and echocardiographic evaluation before and 1.5 ± 1.1 years after pregnancy (pregnancy group), whereas forty served as controls matched for age (28.6 ± 4.6 versus 28.5 ± 6.6, p = 0.88), diagnosis, and length of follow-up (2.9 ± 1.4 versus 2.6 ± 1.1, p = 0.23). NYHA functional class remained unchanged in both groups during follow-up. End diastolic and end systolic dimensions and shortening fraction of the morphologic left ventricle also remained unchanged. Furthermore, systemic and subpulmonary ventricular function remained unchanged in the pregnancy and control groups on semiquantitative analysis. Pregnancy, however, was associated with a persisting increase in subpulmonary ventricular size in patients with tetralogy of Fallot (ToF) which was not present in tetralogy controls. Furthermore, diagnosis of ToF was the only predictor of an increase in subpulmonary ventricular size after pregnancy on univariate logistic regression analysis (OR 8.8[95% CI 1.9–41.1], p = 0.006). Conclusions In this longitudinal controlled study amongst women with HD no deleterious midterm effects of pregnancy on clinical status and right and left ventricular function were found. However, pregnancy was associated with a persisting increase in subpulmonary ventricular size, attributable to patients with repaired ToF. This may have prognostic implications and merits further investigation.