Spatial and temporal analysis of filling flow propagation by color M-mode Doppler echocardiography was free of pseudonormalization and correlated well with the invasive variables of left ventricular relaxation.

Abstract-Osteopontin (OPN) is upregulated in several experimental models of cardiac fibrosis and remodeling. However, its direct effects remain unclear. We examined the hypothesis that OPN is important for the development of cardiac fibrosis and remodeling. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, was mediated through the inhibition of OPN expression against cardiac fibrosis and remodeling. Wild-type (WT) and OPN-deficient mice were treated with angiotensin II (Ang II) for 4 weeks. WT mice receiving Ang II were divided into 2 groups: a control group and an Ep treatment group. Ang II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in WT mice. Ep treatment and OPN deficiency could reduce the Ang II-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas Ep-only treatment abolished the development of cardiac hypertrophy. Most compelling, the reduction of cardiac fibrosis led to an impairment of cardiac systolic function and subsequent left ventricular dilatation in Ang II-treated OPN-deficient mice. These results suggest that OPN has a pivotal role in the development of Ang II-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression. Osteopontin (OPN) is reported to be involved in the process of Ang II-induced fibrosis. 3 Furthermore, OPN can interact with various extracellular matrices, including fibronectin and collagen, suggesting its possible role in matrix organization and stability. 4 Recently, it was shown that OPN expression in heart was associated with the development of heart failure. 5 Moreover, in a murine model of myocardial infarction, OPN deficiency caused exaggeration of left ventricular (LV) dilation and reduction of collagen deposition compared with wild-type (WT) mice. 6 These results suggest that OPN has a pivotal role in cardiac fibrosis and cardiac remodeling.More recently, an important link was suggested in Ang II-induced cardiac fibrosis between OPN and Ald. Ang II induced inflammatory damage in coronary arteries and OPN expression, and eplerenone (Ep), a novel Ald receptor antagonist, could inhibit the OPN expression and ameliorate the Ang II-induced inflammatory damage to coronary arteries. 7 These results suggested that (1) OPN-mediated vascular inflammation might be part of the mechanism by which the renin-angiotensin-aldosterone system participates in the development of cardiac fibrosis and (2) the effect of Ep on the inhibition of vascular inflammation might be modulated by suppressing OPN expression.To investigate whether OPN plays a pivotal role in cardiac fibrosis and remodeling, we treated OPN-deficient (OPN Ϫ/Ϫ ) mice with Ang II and compared them with WT mice treated with Ang II alone or with Ang II and Ep. Herein, we report the role of OPN and the relationship between OPN and Ald ...

The beneficial effects of pravastatin on DHF and structural remodeling are through cholesterol- independent mechanism of statins or "pleiotropic" effects of statins involving improving or restoring endothelial function and decreasing vascular inflammation. These findings suggest the potential involvement of ROCK1. Thus, treatment with pravastatin might be beneficial in patients with DHF.

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Therapy with valsartan may have adverse effects on survival rate concomitant with the progression of cardiac remodeling owing to impaired VEGF-mediated angiogenesis. Therapy with enalapril has a neutral effect on VEGF-mediated angiogenesis, leading to the suppression of cardiac remodeling and an increase in life expectancy.

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This study examined the effects of long-term treatments with the angiotensin-converting enzyme inhibitor, enalapril, and the calcium antagonist, amlodipine, on the morphologic changes, progressive left ventricular dysfunction, and gene expression of the ryanodine receptor (RyR) and phospholamban (PLN) in dilated cardiomyopathy. From the ages of 5 through 20 weeks, dilated cardiomyopathic hamsters, BIO53.58 (BIO), and control hamsters, F1b, orally received either enalapril or amlodipine. Cardiac function was assessed by echocardiography. At the age of 20 weeks, the collagen volume fractions were analyzed by the stereologic method. RyR and PLN messenger RNAs (mRNAs) were examined by Northern blot in the amlodipine group. In BIO, the reduction of left ventricular percentage of fractional shortening was attenuated in the enalapril group (p < 0.05) and amlodipine group (p < 0.001), and the increase in the collagen volume fraction and the loss of myocytes were suppressed in the amlodipine group compared with the untreated group. RyR mRNA level decreased in BIO (p < 0.01) compared with F1b, but PLN mRNA level was unchanged. RyR and PLN mRNA levels were unaffected by the treatment with amlodipine. Enalapril and amlodipine prevent progressive remodeling and reduce cardiac dysfunction in BIO. Amlodipine prevents fibrosis and cell death without modifying RyR and PLN mRNA levels in BIO.

Objective: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging (HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction. Methods: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction. In the apical views myocardial CI (CI myo ) was quantified in five myocardial segments. The CI from the left ventricular blood pool adjacent to the segment was also measured in dB and subtracted from the CI myo (relative CI (RelCI)). Results: CI had a logarithmic correlation and the calculated signal power a strong linear correlation with Levovist concentration in vitro. Thus, a difference in CI of X dB indicates a microbubble concentration ratio of 10 X/10 . In normal control subjects, CI myo differed between the five segments (p , 0.0001), with a lower CI myo in deeper segments. However, RelCI did not differ significantly between segments (p = 0.083). RelCI was lower (p , 0.0001) in the 39 infarct segments (mean (SD) 218.6 (2.8) dB) than in the 55 normal segments (mean (SD) 215.1 (1.6) dB). RelCI differed more than CI myo between groups. Conclusions: The new quantitative method described can overcome the acoustic field inhomogeneity in evaluation of myocardial perfusion during MCE. RelCI represents the ratio of myocardium to blood microbubble concentrations and may correctly reflect myocardial blood volume fraction. M icrobubble concentration within tissue during myocardial contrast echocardiography (MCE) reflects the myocardial blood volume per unit volume (that is, myocardial blood volume fraction).1 2 The contrast signal intensity (CI) on greyscale B mode harmonic imaging after intravenous injection of ultrasound contrast agents has been suggested to reflect the microbubble concentration 3 4 and is used clinically as a quantitative measure to allow estimation of myocardial blood volume.2 5-8 Harmonic power Doppler imaging (HPDI), which has advantages over B mode imaging in opacification of the myocardium, has been used during MCE.9-14 Although animal experiments have shown that the severity of coronary stenosis can be assessed by quantitative analysis of HPDI, 9 15 some problems remain regarding quantitative assessment of myocardial blood volume with HPDI: the lack of detailed information regarding the relation between microbubble concentration and CI of HPDI; and the inhomogeneity of the insonified ultrasound field during MCE. As CI is dependent on the acoustic pressure, [16][17][18] comparison of myocardial CI (CI myo ) between myocardial...