Ulmonary arterioles ,75 mm and the Tunicamycin pulmonary gene expression of IL-19 (Figure 2). To understand better the link between inflammatory phenotype and RV adaptation to the increased afterload, we also looked for correlations between Ees/Ea ratio and different inflammatory determinants. There was a positive correlation between RV Ees/ Ea ratio and RV protein expression of cytoprotective and antiinflammatory HO-1 (Figure 4C) and a negative correlation between with RV ICAM-2 gene expression (Figure 4C).DiscussionThe present results suggest that decreased HO-1 expression and local activation of inflammatory processes are associated to both pulmonary vascular and RV remodeling in pulmonary hypertension on six-month chronic systemic-to-pulmonary shunting in growing piglets. We previously reported on RV failure induced by 6 months of aorta-pulmonary shunting in growing GNF-7 cost piglets [8]. The present study further explored pulmonary hemodynamics and associated biological changes in these animals. Pulmonary artery impedance measured at 0Hz (Z0) and characteristic impedance (Zc) were increased, which is in keeping with previous report on 3-month piglets [21]. Right ventricular afterload and hydrolic load is best described by a pulmonary arterial impedance (PVZ) spectrum, which integrates pulmonary vascular resistance (PVR), elastance,and wave reflection [16,21]. Increases in Z0, or total PVR, calculated as Ppa/Q, may be related with the changes in medial thickness in distal and resistive arterioles whereas increases in characteristic impedance (Zc), ratio between the inertance and compliance of the proximal pulmonary arterial tree [21], could be interpreted as a decrease of pulmonary artery compliance related with structural and/or functional modifications in proximal pulmonary artery. PVR was defined by multipoint mPAP-flow plots. This approach is superior to single point PVR calculations as the slope of mPAP-flow may be less than predicted by the PVR equation because of recruitment, distension or both [22]. Inflammation has been shown to play roles in human and experimental pulmonary hypertension (PH) and is increasingly recognized as a major pathogenic component of the pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) [23]. Moreover, disturbances in homeostatic processes regulating neurohumoral activation, oxidative stress, inflammation and apoptosis have also been suggested to participate to RV failure in PH [24]. We have recently reported that RV failure on prolonged systemic-to-pulmonary shunting in growing piglets [8] and on transient pulmonary artery banding in dogs [9,10] are associated with increased activation of apoptosis and inflammation, including overexpressions of pro-inflammatory cytokines. This reinforces the notion that inflammation seems to play crucial roles in the pathogenesis of PAH and RV failure. In the present study, pulmonary expressions of ICAM-1 and ICAM-2 were increased after 6-month systemic-to-pulmonary shunting, while VCAM-1 expression did not change. The ICAM glycoproteins which are normally weakly expressed by endothelial cells, have been shown to be upregulated after injury and 23977191 responsible for the orchestration of the recruitment and the attachment of inflammatory cells to the endothelium. This represents a marker of endothelial activation [25], acting as a prelude to the migration of inflammatory cells into other vascular layers and probably contributing to the vascular remodeling. Pulmonary overexp.Ulmonary arterioles ,75 mm and the pulmonary gene expression of IL-19 (Figure 2). To understand better the link between inflammatory phenotype and RV adaptation to the increased afterload, we also looked for correlations between Ees/Ea ratio and different inflammatory determinants. There was a positive correlation between RV Ees/ Ea ratio and RV protein expression of cytoprotective and antiinflammatory HO-1 (Figure 4C) and a negative correlation between with RV ICAM-2 gene expression (Figure 4C).DiscussionThe present results suggest that decreased HO-1 expression and local activation of inflammatory processes are associated to both pulmonary vascular and RV remodeling in pulmonary hypertension on six-month chronic systemic-to-pulmonary shunting in growing piglets. We previously reported on RV failure induced by 6 months of aorta-pulmonary shunting in growing piglets [8]. The present study further explored pulmonary hemodynamics and associated biological changes in these animals. Pulmonary artery impedance measured at 0Hz (Z0) and characteristic impedance (Zc) were increased, which is in keeping with previous report on 3-month piglets [21]. Right ventricular afterload and hydrolic load is best described by a pulmonary arterial impedance (PVZ) spectrum, which integrates pulmonary vascular resistance (PVR), elastance,and wave reflection [16,21]. Increases in Z0, or total PVR, calculated as Ppa/Q, may be related with the changes in medial thickness in distal and resistive arterioles whereas increases in characteristic impedance (Zc), ratio between the inertance and compliance of the proximal pulmonary arterial tree [21], could be interpreted as a decrease of pulmonary artery compliance related with structural and/or functional modifications in proximal pulmonary artery. PVR was defined by multipoint mPAP-flow plots. This approach is superior to single point PVR calculations as the slope of mPAP-flow may be less than predicted by the PVR equation because of recruitment, distension or both [22]. Inflammation has been shown to play roles in human and experimental pulmonary hypertension (PH) and is increasingly recognized as a major pathogenic component of the pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) [23]. Moreover, disturbances in homeostatic processes regulating neurohumoral activation, oxidative stress, inflammation and apoptosis have also been suggested to participate to RV failure in PH [24]. We have recently reported that RV failure on prolonged systemic-to-pulmonary shunting in growing piglets [8] and on transient pulmonary artery banding in dogs [9,10] are associated with increased activation of apoptosis and inflammation, including overexpressions of pro-inflammatory cytokines. This reinforces the notion that inflammation seems to play crucial roles in the pathogenesis of PAH and RV failure. In the present study, pulmonary expressions of ICAM-1 and ICAM-2 were increased after 6-month systemic-to-pulmonary shunting, while VCAM-1 expression did not change. The ICAM glycoproteins which are normally weakly expressed by endothelial cells, have been shown to be upregulated after injury and 23977191 responsible for the orchestration of the recruitment and the attachment of inflammatory cells to the endothelium. This represents a marker of endothelial activation [25], acting as a prelude to the migration of inflammatory cells into other vascular layers and probably contributing to the vascular remodeling. Pulmonary overexp.
