dinoprost and Ventricular-Dysfunction--Left

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD).. We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047).. In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD.

Topics: Aged; Blood Pressure; Brachial Artery; Cross-Sectional Studies; Dietary Supplements; Dinoprost; Double-Blind Method; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Nitroglycerin; Placebos; Risk Factors; Superoxide Dismutase; Ubiquinone; Ventricular Dysfunction, Left

Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modern pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malondialdehyde (MDA) and isoprostanes are often used as markers of lipid peroxidation and oxidative stress. We also studied whether long-term treatment with isosorbide-5-mononitrate (IS-5-MN) in combination with standard HF therapy affects P-MDA levels in patients with evidence of left ventricular (LV) dysfunction following acute myocardial infarction (AMI).. Ninety-two patients with clinical or echocardiographic evidence of LV-dysfunction following AMI were randomized to treatment with either IS-5-MN or placebo. In a subgroup of 83 patients with available plasma MDA, echocardiography, right-heart catherization, and plasma natriuretic peptides were evaluated. Control subjects were 80 healthy blood donors. A second study group consisted of 56 patients with CHF, evaluated with respect to LV function, brain natriuretic peptide and markers of oxidative stress (P-MDA and 8-isoprostane). The second control group comprised 50 healthy subjects.. Lipid peroxidation measured by P-MDA and 8-isoprostane was not increased in patients with LV dysfunction treated with standard HF therapy. No positive correlation was found to the severity of HF. Long-term IS-5-MN therapy did not influence P-MDA concentrations.. Although results from many experimental and clinical studies suggest that oxidative stress is increased in HF, this may not be true for patients treated with beta blockers and inhibitors of the renin-angiotensin system.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Captopril; Comorbidity; Delayed-Action Preparations; Dinoprost; Female; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Lipid Peroxidation; Losartan; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nitric Oxide Donors; Oxidative Stress; Ramipril; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

Chronic obstructive pulmonary disease (COPD) augments the likelihood of having left ventricular diastolic dysfunction (LVDD)-precursor of heart failure with preserved ejection fraction (HFpEF). LVDD shares overlapping symptomatology (cough and dyspnea) with COPD. Stress induced LVDD is indicative of masked HFpEF. Our aim was to evaluate the predictive value of inflammatory, oxidative stress, cardio-pulmonary and echocardiographic parameters at rest for the diagnosis of stress LVDD in non-severe COPD patients, who complain of exertional dyspnea and are free of overt cardiovascular diseases. A total of 104 COPD patients (26 patients with mild and 78 with moderate COPD) underwent echocardiography before cardio-pulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. Patients were divided into two groups based on peak average E/e': patients with stress induced left ventricular diastolic dysfunction (LVDD)-E/e' > 15 masked HFpEF and patients without LVDD-without masked HFpEF. CPET and echocardiographic parameters at rest were measured and their predictive value for stress E/e' was analysed. Markers for inflammation (resistin, prostaglandine E2) and oxidative stress (8-isoprostanes) were also determined. Stress induced LVDD occurred in 67/104 patients (64%). Those patients showed higher VE/VCO2 slope. None of the CPET parameters was an independent predictor for stress LVDD.Except for prostglandine E2, none of the inflammatory or oxidative stress markers correlated to stress E/e'. The best independent predictors for stress LVDD (masked HFpEF) were RAVI, right ventricular parasternal diameter and RV E/A >0.75. Their combination predicted stress LVDD with the accuracy of 91.2%. There is a high prevalence of masked HFpEF in non-severe COPD with exertional dyspnea, free of overt cardiovascular disease. RAVI, right ventricular parasternal diameter and RV E/A >0.75 were the only independent clinical predictors of masked HFpEF. 288.

Topics: Aged; Biomarkers; Dinoprost; Dinoprostone; Female; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Resistin; Severity of Illness Index; Ventricular Dysfunction, Left

Glucagon-like peptide-1 (GLP-1) has protective effects in the heart. We hypothesized that GLP-1 would mitigate coronary microvascular and left ventricular (LV) dysfunction if administered after cardiac arrest and resuscitation (CAR). Eighteen swine were subjected to ventricular fibrillation followed by resuscitation. Swine surviving to return of spontaneous circulation (ROSC) were randomized to receive an intravenous infusion of either human rGLP-1 (10 pmol·kg(-1)·min(-1); n = 8) or 0.9% saline (n = 8) for 4 h, beginning 1 min after ROSC. CAR caused a decline in coronary flow reserve (CFR) in control animals (pre-arrest, 1.86 ± 0.20; 1 h post-ROSC, 1.3 ± 0.05; 4 h post-ROSC, 1.25 ± 0.06; P < 0.05). GLP-1 preserved CFR for up to 4 h after ROSC (pre-arrest, 1.31 ± 0.17; 1 h post-ROSC, 1.5 ± 0.01; 4 h post-ROSC, 1.55 ± 0.22). Although there was a trend toward improvement in LV relaxation in the GLP-1-treated animals, overall LV function was not consistently different between groups. 8-iso-PGF(2α), a measure of reactive oxygen species load, was decreased in post-ROSC GLP-1-treated animals [placebo, control (NS): 38.1 ± 1.54 pg/ml; GLP-1: 26.59 ± 1.56 pg/ml; P < 0.05]. Infusion of GLP-1 after CAR preserved coronary microvascular and LV diastolic function. These effects may be mediated through a reduction in oxidative stress.

Topics: Animals; Antioxidants; Cardiopulmonary Resuscitation; Coronary Circulation; Dinoprost; Endothelium, Vascular; Female; Glucagon-Like Peptide 1; Heart Arrest; Heart Ventricles; Humans; Male; Microvessels; Reactive Oxygen Species; Swine; Ventricular Dysfunction, Left; Ventricular Fibrillation

Xanthine oxidase-derived superoxide production and oxidative stress contribute to the development of diabetic complications including diabetic cardiomyopathy. We hypothesized that xanthine oxidase-inhibitor allopurinol (ALP) may decrease hyperglycemia-induced oxidative stress, ameliorate cardiomyocyte hypertrophy and fibrosis, and attenuate the development of left ventricle (LV) diastolic dysfunction in rats with streptozotocin (STZ)-induced diabetes.. Control Sprague Dawley (C) or streptozotocin-induced diabetic (D) rats were either untreated or treated with allopurinol (100 mg/kg/day) for 4 weeks starting at 1 week after streptozotocin injection. Free 15-F2t-isoprostane, a specific indicator of oxidative stress was measured by enzymatic immunoassay. The cardiomyocyte cross-sectional area was assessed by hematoxylin and eosin-stained paraffin-embedded sections of LVs. Myocardial collagens I and III were assessed by immunol histochemistry and Western blotting. Echocardiography was performed to characterize cardiac structure and function.. In diabetic rats, both plasma and cardiac tissue levels of free 15-F2t-isoprostane were increased (p < 0.05 vs. control), accompanied with significant increase (p < 0.05 vs. control) in cross-section area and myocardial collagen deposition of LV cardiomyocyte. Echocardiography in diabetic rats showed that LV weight/body weight ratio was significantly higher than in control rats, whereas the levels of LV end-diastolic volume and stroke volume were decreased (all p < 0.05 diabetic vs. control). All these changes were either attenuated or prevented by allopurinol. In addition, LV ejection fraction in diabetic rats treated with allopurinol was higher than that in untreated diabetic rats (p < 0.05).. Allopurinol can attenuate hyperglycemia-induced oxidative stress, ameliorate cardiomyocyte hypertrophy and fibrosis and subsequently prevent left ventricular dysfunction in early diabetes.

Topics: Allopurinol; Animals; Antimetabolites; Blotting, Western; Collagen Type I; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Dinoprost; Echocardiography; Immunoenzyme Techniques; Isoprostanes; Male; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction, Left

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.

Topics: Allopurinol; Analysis of Variance; Animals; Antioxidants; Atrasentan; Biomarkers; Cyclic N-Oxides; Dinoprost; Disease Models, Animal; Endothelin A Receptor Antagonists; Endothelin-1; Fibrosis; Gout Suppressants; Hypertrophy, Left Ventricular; Hyperuricemia; Isoprostanes; Male; Myocardial Infarction; Myocardium; Oxidative Stress; Pyrrolidines; Rats; Rats, Wistar; Receptor, Endothelin A; RNA, Messenger; Spin Labels; Superoxides; Time Factors; Up-Regulation; Uric Acid; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Xanthine Oxidase