A first dedicated heart valve unit: safe and streamlined patient care for the rapidly growing field of transcatheter heart valve interventions

Abstract Background A dedicated Heart Valve Unit was launched in 2018 to meet the demands of the growing transcatheter heart valve program by optimizing patient care in a single dedicated unit. Purpose To assess the performance of the heart valve unit (all steps of patient care in a single unit with intermediate care facilities) over a conventional approach (preparation on a normal ward, postprocedural intensive care unit (ICU) monitoring and transfer to an additional monitoring ward before discharge) in a high volume center. Methods Retrospective analysis including patients undergoing transcatheter mitral or tricuspid valve repair who were admitted to the Heart Valve Unit (02/2018–01/2020)…

The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity.

Objective In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. Methods Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was adminis…

In vitro and in vivo characterization of a new organic nitrate hybrid drug covalently bound to pioglitazone.

<b><i>Background/Aims:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor γ agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. <b><i>Methods:</i></b> In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. <b><i>Results:</i></…

Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1—evidence for direct and indirect antioxidant actions of bilirubin

Heme oxygenase-1 (HO-1) is highly protective in various pathophysiological states such as cardiovascular and neurodegenerative diseases. HO-1-derived bilirubin is an efficient scavenger of reactive oxygen and nitrogen species (RONS). It remains to determine whether conversion of biliverdin to bilirubin is an essential step for HO-1-conferred protection of endothelial cells. RONS scavenging activities of biliverdin versus bilirubin were assessed by different RONS generating systems and detection techniques. We also silenced the biliverdin reductase (BVR) or HO-1 gene in cultured primary human endothelial cells (HUVECs) and measured the effect on RONS formation upon stimulation with lipopolys…

Value of color doppler jet area for grading regurgitation severity in patients with secondary mitral regurgitation - better than its reputation?

Pentaerithrityl tetranitrate improves angiotensin II induced vascular dysfunction via induction of heme oxygenase-1

The organic nitrate pentaerythritol tetranitrate is devoid of nitrate tolerance, which has been attributed to the induction of the antioxidant enzyme heme oxygenase (HO)-1. With the present study, we tested whether chronic treatment with pentaerythritol tetranitrate can improve angiotensin II–induced vascular oxidative stress and dysfunction. In contrast to isosorbide-5 mononitrate (75 mg/kg per day for 7 days), treatment with pentaerythritol tetranitrate (15 mg/kg per day for 7 days) improved the impaired endothelial and smooth muscle function and normalized vascular and cardiac reactive oxygen species production (mitochondria, NADPH oxidase activity, and uncoupled endothelial NO synthase)…

The AMP-Activated Protein Kinase Plays a Role in Antioxidant Defense and Regulation of Vascular Inflammation

Cardiovascular diseases represent the leading cause of global deaths and life years spent with a severe disability. Endothelial dysfunction and vascular oxidative stress are early precursors of atherosclerotic processes in the vascular wall, all of which are hallmarks in the development of cardiovascular diseases and predictors of future cardiovascular events. There is growing evidence that inflammatory processes represent a major trigger for endothelial dysfunction, vascular oxidative stress and atherosclerosis and clinical data identified inflammation as a cardiovascular risk factor on its own. AMP-activated protein kinase (AMPK) is a central enzyme of cellular energy balance and metaboli…

Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function

Abstract Aims Doxorubicin (DOX) is an important drug for the treatment of various tumor entities. However, the occurrence of heart failure limits its application. This study investigated differential gene expression profiles in the left and right ventricles of DOX treated mice with either preserved or impaired myocardial function. We provide new mechanistic insights into the pathophysiology of DOX-induced heart failure and have discovered pathways that counteract DOX-induced cardiotoxicity. Main methods We used in total 48 male mice and applied a chronic low dose DOX administration (5 mg/kg per injection, in total 20 mg/kg over 4 weeks) to induce heart failure. Echocardiographic parameters …

Hyperglycemia and oxidative stress in cultured endothelial cells – a comparison of primary endothelial cells with an immortalized endothelial cell line

Diabetes mellitus is a major risk factor for the development of cardiovascular disease and oxidative stress plays an important role in this process. Therefore, we investigated the effects of hyperglycemia on the formation of reactive oxygen species (ROS) and nitric oxide/cGMP signaling in two different endothelial cell cultures. Human umbilical vein endothelial cells (HUVEC) and EA.hy 926 cells showed increased oxidative stress and impaired NO-cGMP signaling in response to hyperglycemia. The major difference between the two different cell types was the dramatic decrease in viability in HUVEC whereas EA.hy cells showed rather increased growth under hyperglycemic conditions. Starvation led to…

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial …

Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents. The mechanisms underlying nitrate tolerance remain incompletely defined and are likely multifactorial. One mechanism seems to be a diminished bioconversion of nitroglycerin, another seems to be the induction of vascular oxidative stress, and a third may include neurohumoral adaptations. Recent studies have revealed that mitochondrial reactive oxygen…

Mitochondrial aldehyde dehydrogenase (ALDH-2)--maker of and marker for nitrate tolerance in response to nitroglycerin treatment.

The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Long-term nitrate treatment also is associated with decreased vascular responsiveness caused by changes in intrinsic mechanisms of the tolerant vasculature itself. According to the oxidative stress concept, increased vascular superoxide and peroxynitrite production as well as an increased sensitivity to vasoconstrictors secondary to activation of protein kinase C as well as vascular NADPH oxidases contribute to the development of tolerance. Recent experimental work has defined new tolerance mechanisms, including inhibition of the enzyme that bioactivates …

Abstract 412: The Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin Improves Diabetic Complications in the Streptozotocin Type 1 Diabetes Mellitus Model by Interfering With Glucotoxicity and Rescue of Beta-Cell Function

Objectives: In diabetes, cardiovascular complications are associated with endothelial dysfunction and oxidative stress. Empagliflozin (Empa), as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i) in clinical development, offers a promising novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with Empa could improve endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated oxidative stress. Research Design and Methods: Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection Empa…