scholarly journals Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats

2013 ◽  
Vol 305 (10) ◽  
pp. R1102-R1111 ◽  
Author(s):  
I. Tong Mak ◽  
Jay H. Kramer ◽  
Xi Chen ◽  
Joanna J. Chmielinska ◽  
Christopher F. Spurney ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitral Valve ◽  
Blood Cell ◽  
Cardiac Dysfunction ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Brown Norway ◽  
Altered Expression ◽  
Wall Thinning ◽  
Increased Risk

Use of protease inhibitors (PI) in HIV patients is associated with hyperlipidemia and increased risk of coronary heart disease. Chronic systemic and cardiac effects of ritonavir (RTV), a universal PI booster, and Mg supplementation were examined. RTV was administered (75 mg·kg−1·day−1 po) to Lewis×Brown-Norway hybrid (LBNF1) rats for up to 8 wk; significant increases in plasma triglyceride and cholesterol occurred from 8 days to 8 wk. At 5 wk, the expression of selected hepatic genes ( CYP7A1, CITED2, G6PC, and ME-1), which are key to lipid catabolism/synthesis, were altered toward lipogenesis. Dietary Mg supplementation (six-fold higher) completely reversed the altered expression of these genes and attenuated both hypertriglyceridemia and hypercholesterolemia. Neutrophils isolated from the RTV-treated rats displayed a three-fold higher basal and a twofold higher stimulated superoxide production; plasma isoprostane and red blood cell (RBC) GSSG levels were elevated two- to three-fold. All oxidative indices were normalized by Mg supplementation. After 5 wk, RTV caused significant decreases in cardiac left ventricular (LV) shortening fraction and LV ejection fraction; mitral valve early/late atrial ventricular filling (E/A) ratio was reduced accompanied by LV posterior wall thinning. Immunohistochemical staining revealed significant white blood cell (WBC) infiltration (5 wk) and prominent fibrosis (8 wk) in the RTV hearts. Mg supplementation attenuated RTV-induced declines in systolic and diastolic (improved mitral valve E/A ratio) function (>70%), lessened LV posterior wall thinning (by 75%), and substantially decreased the pathological markers. The known clinical hyperlipidemia effects of RTV can be mimicked in the LBNF1 rats; in association, systemic oxidative stress and progressive cardiac dysfunction occurred. Remarkably, Mg supplementation alone suppressed RTV-mediated hyperlipidemia, oxidative stress, and cardiac dysfunction.

scholarly journals Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH

2009 ◽  
Vol 297 (1) ◽  
pp. H153-H162 ◽  
Author(s):  
Sabrina Serpillon ◽  
Beverly C. Floyd ◽  
Rakhee S. Gupte ◽  
Shimran George ◽  
Mark Kozicky ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Rat Heart ◽  
Mitochondrial Respiratory Chain ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Posterior Wall Thickness ◽  
Patients With Diabetes ◽  
Protein Kinase C Inhibitor ◽  
Glucose 6 Phosphate Dehydrogenase

Increased oxidative stress is a known cause of cardiac dysfunction in animals and patients with diabetes, but the sources of reactive oxygen species [e.g., superoxide anion (O2−)] and the mechanisms underlying O2− production in diabetic hearts are not clearly understood. Our aim was to determine whether NADPH oxidase (Nox) is a source of O2− and whether glucose-6-phosphate dehydrogenase (G6PD)-derived NADPH plays a role in augmenting O2− generation in diabetes. We assessed cardiac function, Nox and G6PD activities, NADPH levels, and the activities of antioxidant enzymes in heart homogenates from young (9–11 wk old) Zucker lean and obese (fa/fa) rats. We found that myocardial G6PD activity was significantly higher in fa/fa than in lean rats, whereas superoxide dismutase and glutathione peroxidase activities were decreased ( P < 0.05). O2− levels were elevated (70–90%; P < 0.05) in the diabetic heart, and this elevation was blocked by the Nox inhibitor gp-91ds-tat (50 μM) or by the mitochondrial respiratory chain inhibitors antimycin (10 μM) and rotenone (50 μM). Inhibition of G6PD by 6-aminonicotinamide (5 mM) and dihydroepiandrosterone (100 μM) also reduced ( P < 0.05) O2− production. Notably, the activities of Nox and G6PD in the fa/fa rat heart were inhibited by chelerythrine, a protein kinase C inhibitor. Although we detected no changes in stroke volume, cardiac output, or ejection fraction, left ventricular diameter was slightly increased during diastole and systole, and left ventricular posterior wall thickness was decreased during systole ( P < 0.05) in Zucker fa/fa rats. Our findings suggest that in a model of severe hyperlipidema and hyperglycemia Nox-derived O2− generation in the myocardium is fueled by elevated levels of G6PD-derived NADPH. Similar mechanisms were found to activate O2− production and induce endothelial dysfunction in aorta. Thus G6PD may be a useful therapeutic target for treating the cardiovascular disease associated with type 2 diabetes, if second-generation drugs specifically reducing the activity of G6PD to near normal levels are developed.

scholarly journals Liraglutide protects cardiac function in diabetic rats through the PPARα pathway

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cardiac Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Serum Adiponectin ◽  
Diabetic Rat ◽  
Lv Function ◽  
High Dose ◽  
And Oxidative Stress

Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 (GLP-1) analog, liraglutide, would attenuate cardiac dysfunction in diabetic rats. A total of 24 Sprague–Dawley (SD) rats were divided into two groups fed either a normal diet (normal, n=6) or a high-fat diet (HFD, n=18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into three subgroups receiving vehicle (diabetic, n=6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n=6), or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n=6). Metabolic parameters, systolic blood pressure (SBP), heart rate (HR), left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, nitric oxide (NO). Liraglutide improved insulin resistance, serum adiponectin, NO, HR, and LV function and reduced blood triglyceride (TG), total cholesterol (TC) levels, and oxidative stress. Moreover, liraglutide increased heart nuclear receptor subfamily 1, group H, member 3 (Nr1h3), peroxisome proliferator activated receptor (Ppar) α (Pparα), and Srebp expression and reduced diacylglycerol O-acyltransferase 1 (Dgat) and angiopoietin-like 3 (Angptl3) expression. Liraglutide prevented cardiac dysfunction by activating the PPARα pathway to inhibit Dgat expression and oxidative stress in diabetic rats.

Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model

Heart ◽  
2018 ◽  
Vol 104 (24) ◽  
pp. 2026-2034 ◽  
Author(s):  
Gianluigi Pironti ◽  
Alex Bersellini-Farinotti ◽  
Nilesh M Agalave ◽  
Katalin Sandor ◽  
Teresa Fernandez-Zafra ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Heart Failure ◽  
Mouse Model ◽  
Posttranslational Modifications ◽  
Contractile Function ◽  
Joint Inflammation ◽  
Left Ventricular ◽  
Increased Risk ◽  
Fractional Shortening

ObjectivesPatients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA.MethodsThe collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis.ResultsHearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress.ConclusionsThis study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.

scholarly journals Effect of Sodium Valproate on Cardiac Function in Epileptic Children by Tissue Doppler Echocardiography

2020 ◽  
Author(s):  
Ali Kamani ◽  
Hadis Omidi ◽  
Fatemeh Dorreh ◽  
Fakhredin Shariatmadari ◽  
Yazdan Ghandi
Keyword(s):  
Ventricular Function ◽  
Cardiac Dysfunction ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Control Group ◽  
Oxidative Balance ◽  
Increased Risk ◽  
Epileptic Children ◽  
Pulsed Wave Doppler

The antiepileptic Valproic acid (VPA) changes the oxidative/ anti-oxidative balance that results in oxidative stress and maybe an increased risk of cardiac dysfunction. The aim of this study was to investigate the effect of VPA on ventricular function in epileptic children. We designed a study to evaluate ventricular function in epileptic children who had received VPA for at least one year. All subjects were evaluated using standard echocardiography, pulsed wave Doppler (PWD), and tissue Doppler imaging (TDI). This study consisted of 60 patients with epilepsy (mean age 10.30±3.21 years) and 60 healthy subjects in the control group (mean age 10.28±3.18 years). The duration of antiepilepsy medication ranged from 1.4 to 10 years, and the dose of VPA was 5-30 mg/kg. The ejection fraction and fractional shortening (P=0.841 and 0.064, respectively) were not significantly different between the two groups. The present study reports subclinical right and left ventricular systolic and diastolic dysfunction along with longitudinal ventricular motion disorder. It is recommended the evaluation of subclinical cardiac dysfunction in children treated by VPA.

scholarly journals Valsartan Reduces Left Ventricular Hypertrophy in Ovariectomized Spontaneous Hypertensive Rats

2020 ◽  
Vol 33 (4) ◽  
pp. 371-371
Author(s):  
Hong Ding ◽  
Ning-ying Li ◽  
Xiang Zhang ◽  
Pan-pan Zhang ◽  
Jing Yu
Keyword(s):  
Oxidative Stress ◽  
Wall Thickness ◽  
Interventricular Septum ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Hypertensive Rats ◽  
Sham Control ◽  
Ovx Rats

Abstract Objective To investigate the effects of valsartan on left ventricular mass, function, and oxidative stress in ovariectomized spontaneous hypertensive rats (SHR). Methods Twelve-week-old female SHRs were randomly divided into ovariectomy (OVX) control (n = 12), OVX + valsartan (n = 12), sham control (Sham, n = 13), and Sham + valsartan (n = 14) groups. Valsartan (30 mg/kg/day) or double-distilled water was given by oral gavage. After 12 weeks of valsartan or water treatment, left ventricular wall thickness and function, superoxide dismutase (SOD), glutathione peroxidase (GSH), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed. Results There was a significant interaction between ovariectomy and valsartan on interventricular end-diastolic septum thickness (IVSTd), end-systolic interventricular septum thickness (IVSTs), left ventricular end-diastolic posterior wall thickness (LVPWTd), and left ventricular end diastolic diameter (LVEDD) (P &lt; 0.05). Valsartan treatment in OVX rats decreased IVSTd, IVSTs, LVPWTd, and LVPWTs compared to OVX control (P &lt; 0.05). Compared with Sham + control group, LVESP and ±dP/dt of LV were decreased while LVEDP was increased in OVX + control group (all P &lt; 0.05). After valsartan treatment, LVESP and ±dP/dt of LV were increased and LVEDP was decreased in ovariectomized rats (all P &lt; 0.05). Ovariectomy decreased GSH and SOD levels and increased 8-OHdG levels, which were reversed by valsartan treatment (all P &lt; 0.05). Conclusion Valsartan treatment decreases oxidative stress, reduces LV hypertrophy, and improves cardiac function in overiectomized SHR.

Exercise training prevents the development of cardiac dysfunction in the low-dose streptozotocin diabetic rats fed a high-fat diet

2013 ◽  
Vol 91 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Riley A. Epp ◽  
Shanel E. Susser ◽  
Marc P. Morissette ◽  
D. Scott Kehler ◽  
Davinder S. Jassal ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Exercise Training ◽  
Protein Content ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
High Fat ◽  
Altered Expression

This study tested the hypothesis that exercise training would prevent the development of diabetes-induced cardiac dysfunction and altered expression of sarcoplasmic reticulum Ca2 +-transport proteins in the low-dose streptozotocin-induced diabetic rats fed a high-fat diet (HFD+STZ). Male Sprague–Dawley rats (4 weeks old; 125–150 g) were made diabetic using a high-fat diet (40% fat, w/w) and a low-dose of streptozotocin (35 mg·(kg body mass)–1) by intravenous injection. Diabetic animals were divided among a sedentary group (Sed+HFD+STZ) or an exercise-trained group (Ex+HFD+STZ) that accumulated 3554 ± 338 m·day–1 of voluntary wheel running (mean ± SE). Sedentary animals fed a low-fat diet served as the control (Sed+LFD). Oral glucose tolerance was impaired in the sedentary diabetic group (1179 ± 29; area under the curve (a.u.c.)) compared with that in the sedentary control animals (1447 ± 42 a.u.c.). Although left ventricular systolic function was unchanged by diabetes, impaired E/A ratios (i.e., diastolic function) and rates of pressure decay (–dP/dt) indicated the presence of diastolic dysfunction. Diabetes also reduced SERCA2a protein content and maximal SERCA2a activity (Vmax) by 21% and 32%, respectively. In contrast, the change in each parameter was attenuated by exercise training. Based on these data, it appears that exercise training prevented the development of diabetic cardiomyopathy and the dysregulation of sarcoplasmic reticulum protein content in an inducible animal model of type 2 diabetes.

Fgl2 deficiency causes neonatal death and cardiac dysfunction during embryonic and postnatal development in mice

2007 ◽  
Vol 31 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Junwu Mu ◽  
Dawei Qu ◽  
Agata Bartczak ◽  
M. James Phillips ◽  
Justin Manuel ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Cardiac Dysfunction ◽  
Neonatal Death ◽  
Posterior Wall ◽  
Ultrasound Biomicroscopy ◽  
Left Ventricular ◽  
Mode Analysis ◽  
Posterior Wall Thickness ◽  
Perinatal Lethality ◽  
And Function

We hypothesized that cardiac dysfunction was responsible for the high perinatal lethality that we previously reported in fibrinogen-like protein 2 ( Fgl2) knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left ventricular (LV) cardiac structure and function during development in Fgl2 KO and wild-type (WT) mice. The only deaths observed between embryonic day (E)8.5 (onset of heart beating) and postnatal day (P)28 (weaning) were within 3 days after birth, when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments suggested that death was due to acute congestive cardiac failure without evidence of valvular or other obvious cardiac structural abnormalities. Heart rates in Fgl2 KO embryos were significantly reduced at E8.5 and E17.5, and irregular heart rhythms were significantly more common in Fgl2 KO (21/26) than WT (2/21) embryos at E13.5. Indexes of systolic and/or diastolic cardiac function were also abnormal in KO mice at E13.5 and E17.5, in postnatal mice studied at P1, and in KO mice surviving to P28. M-mode analysis showed no difference in LV diastolic chamber dimension, although posterior wall thickness was thinner at P7 and P28 in Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious structural cardiac defects but is associated with a high incidence of neonatal death as well as contractile dysfunction and rhythm abnormalities during embryonic and postnatal development in mice.

Estradiol valerate enhances cardiac function via the Nrf2 signaling pathway to protect against oxidative stress by the Nrf2 signaling pathway in an ovariectomized rat model

2021 ◽  
Vol 27 ◽  
Author(s):  
Xin Qian ◽  
Jiao Wang ◽  
Minghui Cai ◽  
Haijuan Sun ◽  
Han Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Estradiol Valerate ◽  
Sham Operation ◽  
Antioxidant Genes ◽  
Bilateral Ovariectomy ◽  
Increased Risk ◽  
Nrf2 Signaling Pathway

Background: The increased risk of cardiovascular disease (CVD) in postmenopausal women and ovariectomized patients suggests that estrogen has a protective effect on cardiac function. Oxidative stress is the main cause of CVD, and the cellular defensive Nrf2 antioxidant pathway plays a protective role in various pathologies. However, the regulation of Nrf2 by estrogen has received little attention. Objective: The present study aimed to investigate the role of Nrf2 in the effect of estrogen on the cardiac function. Method:: In the present study, female SD rats were divided into three groups as follows: sham operation (SHAM), bilateral ovariectomy (OVX) and bilateral ovariectomy with estradiol valerate (EV) supplementation (OVX+EV). Vaginal smears and E2 concentrations were used to confirm model success. We compared cardiac morphology and function by echocardiography and HE staining. The levels of oxidative stress markers and antioxidant enzymes as well as protein expression of antioxidant genes were evaluated by Western blotting and immunohistochemistry. Results: Our results showed that supplementation with estrogen restored the parameters to some extent. Left ventricular end diastolic diameter at diastolic （LVID;d） and left ventricular volume at diastolic (LV vol;d) increased but MV E wave/A wave (E/A) significantly decreased. The oxidative stress indicators (malondialdehyde) increased, and the antioxidant activity indicators, such as superoxide dismutase (SOD) and catalase (CAT), decreased. Further, the expression of most Nrf2 antioxidant pathway-related proteins in the heart decreased after ovariectomy. Conclusion: The present study demonstrated that estrogen may protect cardiac function by regulating antioxidant capacity through the Nrf2 pathway.

scholarly journals Utilization of intra-aortic balloon pump to allow MitraClip procedure in patients with non-coapting mitral valve leaflets: a case series

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Ran Eliaz ◽  
Anna Turyan ◽  
Ronen Beeri ◽  
Mony Shuvy
Keyword(s):  
Heart Failure ◽  
Mitral Valve ◽  
Multiorgan Failure ◽  
Case Series ◽  
Transoesophageal Echocardiography ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Remodelling ◽  
Intra Aortic Balloon Pump ◽  
Annular Dilatation

Abstract Background The MitraClip (MC) procedure was designed for high-risk surgical patients with severe mitral regurgitation (MR). Some patients do not meet the required anatomical criteria due to advanced left ventricular remodelling and mitral annular dilatation leading to leaflet tethering and insufficient coaptation surface. Theoretically, ‘temporary remodelling’ of the mitral valve apparatus by pharmacological and/or mechanical support using intra-aortic balloon pump (IABP) could improve leaflets coaptation. Case summary We report a case series of four patients with severe MR and non-coapting leaflets who underwent MC implantation. Sufficient coaptation was achieved only after insertion of IABP. The first patient presented with worsening heart failure and severe MR after a non-reperfused posterior wall myocardial infarction (MI), underwent a successful procedure with good results. The second patient presented with worsening heart failure secondary to rheumatic MR, and underwent MC procedure with good results after the insertion of IABP. The third patient developed worsening heart failure and severe MR 2 months after an acute inferior-lateral MI, and underwent a successful procedure. The fourth patient presented with respiratory failure, the patient underwent the procedure, but unfortunately died a few days following the procedure from multiorgan failure. In each case, the insertion of the IABP decreased annular mitral diameter and increased the coaptation surface as assessed by transoesophageal echocardiography. Discussion For patients suffering from symptomatic severe MR who are not suitable candidates for MC procedure, IABP system enabled us to overcome mitral leaflet gap and complete the MC procedure successfully.

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