Right ventricular (RV) response to exercise or pharmacological stress is not well documented in pulmonary hypertension (PH). We investigated the relationship between RV reserve and ventricular-arterial coupling.Surgical ligation of the left pulmonary artery was performed in 13 Large White piglets (PH group), thereafter weekly embolisations of the right lower lobe were performed for 5 weeks. A control group of six piglets underwent sham procedures. Right heart catheterisation and echocardiography were performed at week 6. Pressure-volume loops were recorded before and after dobutamine infusion.Induction of experimental PH resulted in a higher mean±SD pulmonary artery pressure (34±9 versus 14±2 mmHg; p<0.01) and in a lower ventricular-arterial coupling efficiency (0.66±0.18 versus 1.24±0.17; p<0.01) compared with controls at 6 weeks. Dobutamine-induced relative changes in RV stroke volume index (SVI) and end-systolic elastance were lower in the PH group (mean±SD 47±5% versus 20±5%, p<0.01, and 81±37% versus 32±14%, p<0.01, respectively). Change in SVI was strongly associated with resting ventricular-arterial coupling (R 2 =0.74; p<0.01). RV reserve was associated with ventricular-arterial coupling in a porcine model of chronic pressure overload. @ERSpublications Dobutamine testing in right ventricular pressure overload: a potentially useful method to assess contractile reserve
Temporary support of the failing RV after LVAD implantation using temporary vein and the pulmonary artery RVAD is a promising therapeutic option. This approach provides adequate LVAD pre- and afterload and is associated with significantly less thromboembolic complications.
An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.
Elimination of senescent cells (SnC) is anti-atherogenic, but the specific contribution of senescent vascular endothelial cells (EC) is unknown. We inactivated angiopoietin like-2 (angptl2), a marker of SnEC and a pro-atherogenic cytokine in LDLr
-/-
, hApoB
100
+/+
atherosclerotic (ATX) mice. Three months after a single vascular delivery of a small hairpin (sh)Angptl2 in 3-month old ATX mice using an adeno-associated virus serotype 1 (AAV1), aortic atheroma plaque progression was slowed by 58% (p<0.0001). In the native aortic endothelium,
angptl2
expression was decreased by 80%, in association with a reduced expression of
p21
, a cyclin-dependent kinase inhibitor overexpressed in growth-arrested SnC. Endothelial activation was reduced (lower
Icam-1, Il-1β
and
Mcp-1
expression), decreasing monocyte
Cd68
expression in the endothelium. One week post-injection, the ratio
Bax/Bcl2
increased in the endothelium only, suggesting that
angptl2
+
/p21
+
SnEC were eliminated by apoptosis. Four weeks post-injection, the endothelial progenitor marker
Cd34
increased, suggesting endothelial repair. In arteries of atherosclerotic patients, we observed a strong correlation between
p21
and
ANGPTL2
(r=0.727, p=0.0002) confirming the clinical significance of
angptl2
-associated senescence. Our data suggest that therapeutic down-regulation of vascular
angptl2
leads to the clearance of SnEC by apoptosis, stimulates endothelial repair and reduces atherosclerosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.