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Objectives: Patients may develop liver dysfunction, including liver fibrosis, over the long term following Fontan procedure. Therefore, early detection of liver dysfunction is essential to identify those patients who are at risk. We evaluated various laboratory parameters, including liver biochemical markers, hepatic echography findings, and cardiac catheterization outcomes, at an early stage after undergoing Fontan procedure., Methods: A total of 56 patients who underwent Fontan procedure were included in the study. All patients underwent cardiac catheterization and biochemical markers were evaluated from the samples. Abdominal echography was performed on a subgroup of patients (n = 20) to observe the structure of liver tissues and to measure blood flow in the hepatic vein, portal vein, and hepatic artery., Results: The mean period of time since Fontan procedure was 2.8 ± 2.1 years. There was a significant correlation between venous pressure and serum levels of γ-glutamyltranspeptidase and type IV collagen 7s domain, which indicated a high probability of liver consolidation. The other biochemical markers were normal. Stepwise regression analyses suggested that by using the ratio of hepatic venous flow and type IV collagen 7s collagen domain concentration, inferior vena cava pressure can be predicted., Conclusions: Our study showed that we can predict inferior vena cava pressure using noninvasive abdominal echography and biochemical markers at an early stage after Fontan procedure., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear., Methods: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model., Results: WE OBTAINED THE FOLLOWING RESULTS: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group., Conclusion: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis.

Background: Hypoxic gas ventilation therapy has recently been performed to prevent post-birth increased pulmonary blood flow in cases of congenital heart diseases with increased pulmonary blood flow. However, how the oxygen supply to the tissues changes during breathing a hypoxic gas mixture, remains unknown. The changes in cerebral oxygen saturation and blood supply during hypoxic gas ventilation therapy using a nitrogen gas mixture were studied., Methods and Results: Cerebral regional oxygen saturation (cerebral rSO(2)) was measured by near-infrared spectroscopy, and changes in middle cerebral artery (MCA) blood flow and an index of vascular resistance (RI) were assessed in 8 consecutive patients having congenital heart diseases with increased pulmonary blood flow. In all patients, urinary volume increased significantly, and the respiratory rate showed a clear decrease. Percutaneous oxygen saturation showed no significant change. The average of cerebral rSO(2) was 67.3% before hypoxic gas ventilation, but increased to 69.4%, 69.1%, and 70.7% within 1, 12, and 24 h after initiation of treatment, respectively. MCA blood flow significantly increased in the diastolic phase, and RI significantly improved from 0.80 to 0.68 within 12 h after initiation of therapy., Conclusions: These results indicate that hypoxic gas ventilation therapy does not decrease cerebral oxygen saturation, but safely improves the cerebral blood supply in cases of congenital heart diseases with increased pulmonary blood flow.

Background: In Kawasaki disease (KD), it has been clinically and experimentally reported that post-inflammatory vascular remodeling would induce the development of arteriosclerosis or early onset of atherosclerosis in the future. The effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on continuous vascular remodeling late after Kawasaki disease were clinically evaluated., Patients and Methods: We enrolled and treated a total of 11 KD patients (age range, 7-25 years) with fluvastatin (0.5-0.7 mg/kg/day) for 12 months. All of them had significant coronary aneurysmal or stenotic lesions and more than 3 of the following 5 abnormal findings: reduced %flow-mediated dilatation (%FMD), reduced urinary NOx, elevated high-sensitivity C-reactive protein (hs-CRP), reduced urinary 8-isoprostane, and elevated brachial-ankle pulse wave velocity (baPWV; control, ≤1400 cm/s)., Results: A statistically significant improvement was observed in each biomarker after fluvastatin treatment: %FMD, from 9.29% (3.41)% to 10.55% (3.27)% (p=0.003) after 3 months; NOx/creatinine (cre), from 1.16 (0.54) µmol/mg cre to 1.30 (0.50) µmol/mg cre (p=0.038) after 12 months; baPWV, from 1175.4 (277.3) cm/s to 1031.8 (155.6) cm/s (p=0.009) after 3 months; hs-CRP, from 0.073 (0.035) mg/dl to 0.028 (0.014) mg/dl (p=0.0002) after 3 months; and 8-iso/cre, from 751.8 (241.8) pg/mg cre to 660.0 (198.5) pg/mg cre (p=0.018) after 3 months. No adverse events were clinically observed in the patients., Conclusions: The results of this study suggested that HMG-CoA reductase inhibitors are useful as an alternative therapeutic strategy for stabilizing continuous post-inflammatory vascular remodeling that results in the development of arteriosclerosis late after KD or early onset of atherosclerosis in the future., (Copyright © 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Matrix metalloproteinases (MMPs) contribute to extracellular remodeling in Kawasaki disease (KD). MMP-9 is an essential vasculature-remodeling factor but its role in the vascular lesions of KD is not understood. This study focused on MMP-9 regulation via cytokines in endothelial cells (ECs)., Methods and Results: Plasma and peripheral blood mononuclear cells were obtained from 30 KD patients, and 15 non-febrile and 25 febrile children. Plasma MMP-1, -2, -9, and tissue inhibitor of MMP (TIMP)-1 and -2 were measured by 2-step sandwich ELISA. Immunohistology was performed on coronary arterial lesions (CAL) from a patient who died of KD in the acute phase. MMP-9 mRNA expression in human umbilical ECs (HUVECs) treated with plasma or cytokines, and in mononuclear cells was measured by semi-quantitative reverse transcription-polymerase chain reaction. Plasma MMP-1, -2 and TIMP-2 levels were normal for KD. Plasma MMP-9 and TIMP-1 levels increased during the acute phase of the disease (P<0.001 vs each control). MMP-9 stained diffusely in CAL. MMP-9 mRNA levels were higher in HUVECs treated with plasma in the acute and convalescent phases. Interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha stimulated MMP-9 expression, whereas interferon (IFN)-gamma suppressed it. There was no MMP-9 mRNA elevation in mononuclear cells., Conclusions: ECs are a source of MMP-9 in the vascular lesions of KD. MMP-9 is regulated by cytokines IL-1beta, IL-6, TNF-alpha and IFN-gamma.

We report an infant with Tetralogy of Fallot who had suffered from repetitive attacks of syncope without obvious cyanosis. Careful observation by means of echocardiography and angiography revealed that the attacks resulted from acute coronary artery obstruction due to membranous ridge covering the sinus Valsalva. Surgical resection of the abnormal ridge and repair of Tetralogy of Fallot successfully improved the patient's symptoms. Syncope in children should be extensively investigated to exclude obstruction of the coronary arteries.

Helical computed tomographic angiography with differential color imaging technique clearly demonstrated pulmonary venous obstruction in an infant with total anomalous pulmonary venous drainage before and after operation. This technique is less invasive and provides precise spatial information of complicated vascular anomalies.

We evaluated the change of coronary flow reserve using a Doppler guidewire before and after coronary artery bypass grafting to assess the coronary hemodynamic effect of surgical revascularization in a 13-year-old boy with congenital atresia of the left coronary ostium, which is one of the rarest of the congenital coronary anomalies. Coronary flow reserve in the right coronary artery and left anterior descending artery increased significantly after coronary revascularization, and a microvascular bed developed in the left anterior descending artery.