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Right lung ischemia induces development of contra-lateral pulmonary vasculopathy

Edouard Sage, Olaf Mercier, Philippe Dartevelle, Saadia Eddahibi, Elie Fadel
European Respiratory Journal 2011 38: 3435; DOI:
Edouard Sage
LCE INSERM U999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
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Olaf Mercier
LCE INSERM U999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
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Philippe Dartevelle
LCE INSERM U999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
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Saadia Eddahibi
LCE INSERM U999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
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Elie Fadel
LCE INSERM U999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
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Abstract

Chronic thromboembolic pulmonary hypertension is due to mechanical obstruction by unresolved clots and vasculopathy in the non obstructed vascular lung regions. We tested whether flow induced vascular lesions or endocrine factors released by the ischemic lung account for development of vasculopathy in non obstructed regions.

3 groups of 5 piglets were studied 5 weeks after right pulmonary artery (PA) ligation (PAL group), right pneumonectomy (RP group) or right PA dissection (Sham group). We measured pulmonary vascular resistance, pulmonary arterial vasoreactivity and morphometry, and quantified gene expression of factors involved in vascular smooth muscle cell proliferation IGF, PDGF, VEGF and endothelium-dependent vasoreactivity pathways ET-1, ETAr, ETBr and eNOS.

As compared to RP, PAL animals developed pulmonary vasculopathy in the left lung as assessed by increase in pulmonary vascular resistances (p=0.0006), medial hypertrophy of the distal PA (p<0.0001), decreases in both maximal relaxation to acetylcholine (p=0.013) and eNOS gene expression (p=0.041). Left lung IGF (p=0.034), PDGF (p=0.0006) and VEGF (0.0105) gene expressions increased in the PAL group when compared to both RP and Sham. ETAr and ETBr expression was downregulated in both RP (p=0.048 and p=0.039) and PAL (p=0.033 and p=0.028) groups.

Pulmonary vasculopathy is absent in the remaining lung 5 weeks after pneumonectomy and developed in the non obstructed pulmonary territories 5 weeks after right PA ligation suggesting that factors released by the ischemic lung induced vascular remodelling in the contra-lateral lung. This endocrine regulation might implicate release of factors involved in vascular smooth muscle cell proliferation.

  • © 2011 ERS
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Right lung ischemia induces development of contra-lateral pulmonary vasculopathy
Edouard Sage, Olaf Mercier, Philippe Dartevelle, Saadia Eddahibi, Elie Fadel
European Respiratory Journal Sep 2011, 38 (Suppl 55) 3435;

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Right lung ischemia induces development of contra-lateral pulmonary vasculopathy
Edouard Sage, Olaf Mercier, Philippe Dartevelle, Saadia Eddahibi, Elie Fadel
European Respiratory Journal Sep 2011, 38 (Suppl 55) 3435;
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