Increased NAD(P)H oxidase-mediated superoxide production in renovascular hypertension: Evidence for an involvement of protein kinase C

Increased NAD(P)H oxidase-mediated superoxide production in renovascular hypertension: Evidence for an involvement of protein kinase C.BackgroundAngiotensin II infusion has been shown to cause hypertension and endothelial dysfunction and to increase superoxide (O-·2) production in vascular tissue, mainly via an activation of nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]-dependent oxidase, the most significant O-·2 source in endothelial and/or smooth muscle cells. With these studies, we sought to determine whether endothelial dysfunction in renovascular hypertension is secondary to an activation of these oxidases.MethodsEndothelial function in aortas from rats with two kidney-one clip (2K-1C) hypertension and age-matched controls was assessed using isometric tension studies in organ chambers. Changes in vascular O-·2 production were measured using lucigenin-enhanced chemiluminescence and electron spin resonance spectroscopy.ResultsIn hypertensive animals, relaxation to endothelium-dependent (acetylcholine) and endothelium-independent nitrovasodilators (nitroglycerin) was impaired. Constriction to a direct activator of protein kinase C (PKC) phorbol ester 12,13 dibutyrate (PDBu) was enhanced, and vascular O-·2 was significantly increased compared with controls. Vascular O-·2 was normalized by the PKC inhibitor calphostin C, by the inhibitor of flavin-dependent oxidases, diphenylene iodonium, and recombinant heparin-binding superoxide dismutase, whereas inhibitors of the xanthine oxidase (oxypurinol), nitric oxide synthase (NG-nitro-L-arginine) and mitochondrial NADH dehydrogenase (rotenone) were ineffective. Studies of vascular homogenates demonstrated that the major source of O-·2 was a NAD(P)H-dependent oxidase. Incubation of intact tissue with PDBu markedly increased O-·2, the increase being significantly stronger in vessels from hypertensive animals as compared with vessels from controls. Endothelial dysfunction was improved by preincubation of vascular tissue with superoxide dismutase and calphostin C.ConclusionsWe therefore conclude that renovascular hypertension in 2K-1C rats is associated with increased vascular O-·2 leading to impaired vasodilator responses to endogenous and exogenous nitrovasodilators. Increased vascular O-·2 is likely secondary to a PKC-mediated activation of a membrane-associated NAD(P)H-dependent oxidase

Usefulness of 3D-PISA as compared to guideline endorsed parameters for mitral regurgitation quantification.

This study was intended to evaluate the diagnostic value of three dimensional proximal isovelocity surface area (3D PISA) derived effective regurgitant orifice area (EROA) and the accuracy of automatic 3D PISA detection in a population resembling clinical practice. Quantification of mitral regurgitation (MR) remains challenging and 3D PISA EROA is a novel diagnostic tool with promising results. However its' usefulness compared to guideline endorsed parameters has not been shown. In 93 consecutive patients examined in routine practice conventional parameters and 3D-datasets for offline 3D PISA evaluation were recorded. EROA was determined from the largest (peak) PISA and also averaged over systole for meanEROA. Results of 3D PISA calculation were compared with a combination of expert grading by two examiners and two scores for MR grading. In receiver operator characteristic-analysis the meanEROA as determined by 3D PISA had the best diagnostic value (AUC = 0.907 CI 0.832-0.983) as compared to peakEROA (AUC 0.840 CI 0.739-0.941), vena contracta width (AUC 0.831 CI 0.745-0.918) and 2D PISA (AUC 0.747 CI 0.644-0.850). A meanEROA of 0.15 cm2 had a sensitivity of 88.2 % and a specificity of 81.4 % for distinguishing severe from non-severe MR. Semiautomatic 3D PISA detection correlated very well with manually corrected values (r = 0.955). Semiautomatic 3D PISA measurement is feasible in a clinical population and has better diagnostic value compared to 2D PISA. Calculation of mean EROA throughout systole further improves diagnostic value compared to conventional parameters

Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke?

<p>Abstract</p> <p>Background</p> <p>Elevated serum uric acid (SUA) levels can enhance its antioxidant prosperities and reduce the occurrence of cerebral infarction. Significantly elevated SUA levels have been associated with a better prognosis in patients with cerebral infarction; however, the results from some studies on the relationship between SUA and the prognosis of patients with cerebral infarction remain controversial.</p> <p>Methods</p> <p>We analyzed the relationship between SUA and clinical prognosis of 585 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Using multivariate logistic regression modeling, we explore the relationship between SUA levels and patient's clinical prognosis.</p> <p>Results</p> <p>Lower SUA levels at time of admission were observed more frequently in the lowest quintile for patients with severe stroke (P = 0.02). Patients with cerebral infarction patients caused by small-vessel blockage had higher SUA concentrations (P = 0.01) and the lower mRS scores (P < 0.01) were observed in, while the lowest SUA concentrations and the highest mRS scores were seen in patients with cardiogenic cerebral infarction patients. Logistic regression analysis adjusted for confounders confirmed the following independent predictors for young cerebral infarction: uric acid (-0.003: 95%CI 0.994 to 0.999) and platelet (0.004, 95%CI 0.993 to 0.996).</p> <p>Conclusion</p> <p>Elevated SUA is an independent predictor for good clinical outcome of acute cerebral infarction among young adults.</p

Oxidative Stress in Cardiac Tissue of Patients Undergoing Coronary Artery Bypass Graft Surgery: The Effects of Overweight and Obesity

Background. Obesity is one of the major cardiovascular risk factors and is associated with oxidative stress and myocardial dysfunction. We hypothesized that obesity affects cardiac function and morbidity by causing alterations in enzymatic redox patterns. Methods. Sixty-one patients undergoing coronary artery bypass grafting (CABG) were included in the study. Excessive right atrial myocardial tissue emerging from the operative connection to the extracorporeal circulation was harvested. Patients were assigned to control (n=19, body mass index (BMI): 30 kg/m2) groups. Oxidative enzyme systems were studied directly in the cardiac muscles of patients undergoing CABG who were grouped according to BMI. Molecular biological methods and high-performance liquid chromatography were used to detect the expression and activity of oxidative enzymes and the formation of reactive oxygen species (ROS). Results. We found increased levels of ROS and increased expression of ROS-producing enzymes (i.e., p47phox, xanthine oxidase) and decreased antioxidant defense mechanisms (mitochondrial aldehyde dehydrogenase, heme oxygenase-1, and eNOS) in line with elevated inflammatory markers (vascular cell adhesion molecule-1) in the right atrial myocardial tissue and by trend also in serum (sVCAM-1 and CCL5/RANTES). Conclusion. Increasing BMI in patients undergoing CABG is related to altered myocardial redox patterns, which indicates increased oxidative stress with inadequate antioxidant compensation. These changes suggest that the myocardium of obese patients suffering from coronary artery disease is more susceptible to cardiomyopathy and possible damage by ischemia and reperfusion, for example, during cardiac surgery

Transcatheter aortic valve implantation with the new-generation Evolut R™: Comparison with CoreValve® in a single center cohort

The Medtronic Evolut R (EVR) is a novel transcatheter heart valve designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of the new EVR with the established Medtronic CoreValve (CV) system

Transcatheter aortic valve implantation with the new-generation Evolut R™

Background: The Medtronic Evolut R (EVR) is a novel transcatheter heart valve designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of the new EVR with the established Medtronic CoreValve (CV) system. Methods and results: Of 151 patients undergoing transfemoral transcatheter aortic valve implantation with a self-expanding valve at our institution between January 2013 and January 2016, 86 were treated with EVR and 65 with CV. Patients treated with EVR had a significantly lower rate of more-than-mild aortic regurgitation and a higher rate of device success. Recapture maneuvers to optimize valve deployment were performed in 22.1% of the EVR procedures. Transvalvular post-procedural gradients were slightly higher in the EVR group, while no differences were observed in the incidence of safety endpoints at 30 days, vascular complications, or need for permanent pacemaker implantation following asystole or complete atrioventricular block. Conclusions: These initial single-center experience data on the short-term outcomes after EVR valve implantation show a substantially reduced rate of more-than-mild paravalvular regurgitation and higher device success, while 30-day safety outcomes were similar to the CV system. Clinical outcome data from long-term follow-up and larger scale multicenter experience are now necessary