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We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 μg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.

Elderly populations are increasingly represented among patients with acute coronary syndrome (ACS), and advanced age has been identified as an important risk factor for death and adverse outcome in patients with ACS treated invasively. Although considerable data have demonstrated a prognostic benefit of early revascularization in ACS particularly in high-risk patients, elderly patients with ACS are treated invasively less often than younger patients because older age is thought to be an independent predictor of mortality after percutaneous coronary intervention (PCI) in ACS. Over the past 5 years, a total of 54 ACS patients over 85 years old were treated. The 6-month survival rate was around 50% in the non-PCI group (n = 12) and around 80% in the PCI group (n = 42) (P < 0.05). Cardiac death occurred in 6 patients in the PCI group and in 6 patients in the non-PCI group. The rates of both cardiac death and all-cause death were significantly lower in the PCI group. The change in ADL score before and 6 months after the procedure was from 1.57 to 1.59 in the PCI group and from 2.25 to 2.20 in the non-PCI group. PCI for elderly patients with ACS is safe and life saving, and does not reduce the ability to perform activities of daily living. PCI should be recommended even for octo-nonagenerians with ACS.

The ubiquitin (Ub)-proteasome system (UPS) is an important proteolytic mechanism for selecting and digesting cytotoxic proteins. The aim of this study is to elucidate expression and in situ localization of the UPS in the myocardium from patients with dilated cardiomyopathy (DCM) with refractory heart failure. The expression profile of the oxidative stress-induced cytotoxic proteins was also examined. Myocardium was obtained from 26 patients with DCM at the left ventriculoplasty. Ten normal autopsied hearts served as controls. Myocardial expressions of Ub and proteasomes were studied immunohistochemically. Oxidative stresses were examined in point of localization of the oxidation-induced modifier molecules (OMM). The relationship between immunohistochemical results and clinical parameters was also evaluated. Both Ub and proteasomes were stained positive in granular structures accumulating between the myofibrils and adjacent to nuclei in cardiomyocytes. The OMMs were also positive in the same Ub-positive granular structures. The area fraction of Ub, proteasomes and OMM was significantly higher in DCM hearts than in normal controls. Significant positive correlation was observed between the area fractions of Ub and plasma levels of brain natriuretic peptide (p = 0.046) in DCM hearts. In conclusion, enhanced expression of the UPS colocalized with OMM in cardiomyocytes may be involved in the pathophysiology of DCM hearts.

Angiotensin II receptor blockers (ARBs) are suggested to be protective against myocardial hypertrophy and fibrosis, although such beneficial effects remain to be elucidated in the human heart. The aim of the present study was to examine the effect of a novel ARB, olmesartan, on myocardial function of the left ventricle in patients with mildto-moderate hypertension. We investigated 10 patients (6 men and 4 women, 62 +/- 7 years of age) who were stable with a single regimen of amlodipine, which was switched to olmesartan. Before and 8 months after changing medications, patients underwent echocardiographic examination and blood sampling, including measurement of the plasma high-sensitivity C-reactive protein (hsCRP) level. Peak velocities at the mitral annulus were determined by tissue Doppler imaging and used as measures of myocardial function. Olmesartan did not significantly alter blood pressure (BP) (systolic BP, 122 +/- 12 to 121 +/- 8 mmHg, P = 0.9; diastolic BP, 79 +/- 6 to 75 +/- 4 mmHg, P = 0.06) or parameters of global left ventricular systolic and diastolic function. Tissue Doppler imaging, however, revealed significant increases in the systolic (8.2 +/- 1.3 to 8.9 +/- 1.1 cm/s, P < 0.01) and early diastolic (6.7 +/- 0.9 to 7.6 +/- 1.0 cm/s, P = 0.02) velocities at the mitral annulus. This was associated with decreases in the left ventricular mass index (83 +/- 15 to 73 +/- 19 g/m2, P = 0.09) and hsCRP (683 +/- 555 to 655 +/- 450 ng/ml, P = 0.07). In conclusion, olmesartan improves myocardial function independent of BP reduction in hypertensive patients. Attenuated inflammatory changes as well as myocardial hypertrophy may play an important role.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by the progressive replacement of myocardial cells by fat and fibrous tissue. Here we describe the histopathological features of biopsied myocardium from a patient with ARVC. A large amount of adipose tissue was present in the biopsy specimen, and a group of myocardial cells were isolated as an island-like region in the adipose tissue. Electron microscopic examination of cardiomyocytes revealed a large number of intracellular lipid droplets, including some extremely large droplets. Disruptions of the plasma membrane and dissociation of intercellular junctions were associated with discharge of intracellular lipid droplets into the interstitial space. The high accumulation of intracellular lipid droplets may be involved in the pathogenesis of ARVC and may have played an important role in myocardial cell death and progressive replacement of cardiomyocytes by fatty tissue in the current case.

Recent advances in interventional devices and technology have greatly improved the results of percutaneous transluminal angioplasty (PTA), and it is now being widely used. However, it is important to obtain information regarding its results and its long-term patency. We examined the primary success rates and long-term patency in 29 limbs out of 27 patients with superficial femoral artery (SFA) occlusion who underwent PTA with self-expandable stents. Among the 29 lesions, 19 were long occlusions (>10 cm) and 10 were short (<10 cm). Overall primary success was achieved in 26 of the 29 limbs (90%). There were three unsuccessful cases in which the patients were on dialysis and had hard calcification in the arterial walls. After 3 years, primary patency, primary-assisted patency, and secondary-assisted patency were 81%, 86%, and 96%, respectively. In the case of short occlusions (<10 cm), the 3-year patency was 100%. Both the primary success rate and the long-term patency were considerably better than expected. Our results with self-expanding stents were superior to previously reported results and were not inferior to those of surgical bypass. Therefore, PTA may be considered as a good first option for the treatment of SFA occlusions.

Cardiac blood cysts are rarely seen in adult patients and in the right atrium. The origin of cardiac blood cysts is not understood, and several hypotheses have been proposed. We present a rare case of right atrial blood cyst with total occlusion of the right coronary artery (RCA). Inflammatory processes may have played an important role in the development of the cyst, because infiltration of inflammatory cells was observed in the cystic wall. Additionally, total obstruction of the proximal RCA indicated that ischemia and/or infarction in the right atrium might be related to formation of the cyst.

We describe the clinical manifestations of a patient with Churg-Strauss syndrome who presented with severe acute cardiac involvement and whose disease evolved to dilated cardiomyopathy (DCM), with special reference to the histopathological findings. Endomyocardial biopsies, conducted sequentially, three times within 10 months, revealed severe eosinophilic endomyocarditis in the acute phase, interstitial fibrosis in the subacute phase, and endocardial thickening with mural thrombi, at 10 months. Although acute inflammation associated with elevation of eosinophil granule proteins subsided with steroid therapy, left ventricular dilatation with reduced contractility progressed. A subgroup of DCM is not considered to be idiopathic but, rather, an aftereffect of hypereosinophilic heart disease.