Right Ventricular Dyssynchrony in Patients With Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC. CONCLUSIONS: CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

Significance of system L amino acid transporter 1 (LAT-1) and 4F2 heavy chain (4F2hc) expression in human developing intestines.

To clarify the significance of expression of system L amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in the developing intestine, immunohistochemical investigation and molecular analysis were performed in the human embryonic and/or fetal intestines, ranging from 28-30 days to 34-35 weeks gestation. The molecular analysis for the expression of LAT1 and 4F2hc mRNAs was done in the pure epithelial cell samples prepared after laser assisted microdissection. The immunoreactivities against LAT1 and 4F2hc were detected along the basolateral cell membrane of the primitive gut epithelium at 28-30 days gestation. According to advance in gestational age of up to 24-25 weeks gestation, the immunoreactivity of LAT1 was predominantly observed in the supranuclear cytoplasmic localization with a granular or dot-like staining pattern. Up to 8-9 weeks gestation, the immunoreactivity of 4F2hc showed almost the same as that of LAT1. However, after the age of 12-13 weeks gestation, the immunoreactivity of 4F2hc was predominantly localized along the cell membrane of apical surface of the epithelial cells. No apical and linear membranous localization of LAT1 was observed until nearly 20 weeks gestation. In the late gestational stage, both the immunoreactivities against LAT1 and 4F2hc were localized along the apical surface of the epithelial cells. In conclusion, the expression of LAT1 and 4F2hc in early developing intestine suggests they have a more important role in cell proliferation rather than functional differentiation. The predominant cytoplasmic localization of LAT1 during mid-fetal life seems to be largely inactive as amino acid transporter. On the other hand, the apical and linear membranous co-localization of LAT1 and 4F2hc in the late fetal life suggests that these molecules may play a role as a functional amino acid transporter in the fetal intestinal epithelium.