Background-Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating -blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results-Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects (PϽ0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9Ϯ4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22Ϯ8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% (PϽ0.005) along with amelioration of heart failure. Conclusions-Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.
We have developed a system to estimate velocity vector fields inside the cardiac ventricle by echocardiography and to evaluate several flow dynamical parameters to assess the pathophysiology of cardiovascular diseases. A two-dimensional continuity equation was applied to color Doppler data using speckle tracking data as boundary conditions, and the velocity component perpendicular to the echo beam line was obtained. We determined the optimal smoothing method of the color Doppler data, and the 8-pixel standard deviation of the Gaussian filter provided vorticity without nonphysiological stripe shape noise. We also determined the weight function at the bilateral boundaries given by the speckle tracking data of the ventricle or vascular wall motion, and the weight function linear to the distance from the boundary provided accurate flow velocities not only inside the vortex flow but also around near-wall regions on the basis of the results of the validation of a digital phantom of a pipe flow model.
Creation of a large anastomotic space and a smooth aortic arch angle reduced wall shear stress and energy loss, and should improve long-term cardiac performance after the Norwood procedure.
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