-
[show abstract]
[hide abstract]
ABSTRACT: Pulmonary hypertension is rare in chronic respiratory diseases but has a strong impact on the prognosis and is partly underlined by factors other than hypoxaemia. The aim of the present study was to assess the potential role of endothelin-1 (ET-1) and nuclear factor (NF)-kappaB vasoconstrictive pathways in pulmonary hypertension. The effects of ET-1 receptors blockers (BQ 123 and 788) and of genistein were assessed on response to acetylcholine of pulmonary vascular rings from cystic fibrosis (CF) lung transplant recipients (n = 23). NF-kappaB and ET-1 receptor expression was immunodetected in pulmonary arteries and quantitated using Western blotting. ET-1 vascular content was quantitated using ELISA. In total, 14 out of 23 subjects exhibited strongly impaired pulmonary vasodilation (p<0.01 versus nine out of 23 subjects with a normal response) associated with an activation of ET-1 receptors A and NF-kappaB pathways. Genistein restored vasodilation in subjects with an abnormal response. Pulmonary vascular dysfunction is frequent in end-stage CF, involving the NF-kappaB pathway and that of ET-1 through ET-1 receptor A (ETAR). These data leave a conceptual place for ETAR blockers and isoflavones in the management of the devastating vascular complication of chronic obstructive respiratory diseases such as CF.
European Respiratory Journal 05/2009; 34(6):1329-37. · 5.89 Impact Factor
-
Archives de Pédiatrie 07/2008; 15(5):698-701. · 0.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the cellular and histological basis of irreversible pulmonary hypertension (PHT) in the clinical setting of congenital heart disease (CHD).
Although many children with CHD develop pulmonary vascular disease, it is unclear why this complication is reversible after complete repair in some cases but irreversible in others. As failure of endothelial cell apoptosis might lead to intimal proliferation and lack of reversibility of PHT, we investigated this and other key markers of vasoactivity and angiogenesis, in subjects with PHT and CHD.
We assessed anti- and pro-apoptotic markers in vascular and perivascular cells in lung biopsies from 18 patients with CHD; 7 with reversible and 11 with irreversible PHT, and from 6 controls. Immunostaining for eNOS, VEGF and CD34 (markers of vasoactivity and neoangiogenesis) was also performed.
The anti-apoptotic protein Bcl-2 was highly expressed by pulmonary endothelial cells in all cases of irreversible PHT but in no cases of reversible PHT, nor in controls (p<0.001). Intimal proliferation was present in 10/11 irreversible PHT cases but never observed in reversible PHT (p<0.001). Similarly, perivascular inflammatory T-cells expressed more anti-apoptotic proteins in irreversible PHT (p<0.01). Irreversible PHT cases were also more likely to show compensatory up-regulation of VEGF and new small vessel formation at the sites of native vessel stenosis or occlusion (p<0.001).
Irreversible PHT is strongly associated with impaired endothelial cell apoptosis and anti-apoptotic signalling from perivascular inflammatory cells. These changes are associated with intimal proliferation and vessel narrowing and thereby may contribute to clinical outcomes associated with pulmonary hypertension. Markers of apoptosis and angiogenesis were assessed in lung biopsies of subjects with pulmonary hypertension (PHT) due to congenital heart disease (CHD). The anti-apoptotic protein Bcl-2 was strongly expressed by pulmonary endothelial cells in irreversible PHT (n=11) but never in reversible PHT (n=7) (p<0.01). Irreversible PHT was also associated with up-regulation of VEGF and new vessel formation around occluded native vessels (p<0.01).
Archives des maladies du coeur et des vaisseaux 06/2007; 100(5):365-72. · 0.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We retrospectively analyzed the pulmonary biopsies of a Fontan intervention in order to identify predictive markers of its result. The pulmonary biopsies of 17 patients who benefited from the Fontan intervention and 6 controls were studied. The histomorphometric measurements and endothelial expression of vasoactive factors (NO synthase, endothelin-1) and angiogenic factors (VEGF) were analyzed with immunohistochemistry at the level of intra-acini pulmonary arterioles. Eight patients presented a good surgical result (group 1). Distal arterioles presented a thin and regular wall: the NO synthase, endothelin and VEGF expression was low. Nine patients presented a failure of the Fontan operation (group 2). The distal arterioles were slightly musculated (p<0.01 vs. group 1 and group control). The endothelin-1 expression was comparable to that observed in group 1. Conversely, the NO synthase and VEGF expressions were significantly increased in that group (<0.001 vs. group 1 and group control). CONCLUSION: In case of Fontan operation failure, the histological modifications are subtle with a muscular extension of the distal pulmonary arterioles wall. Conversely, a marked increase of NO synthase and VEGF expression is observed which can witness of an endothelial dysfunction. This study could be able to define predictive factors of the evolution and refine the selection of patients candidate for a Fontan operation.
Archives des maladies du coeur et des vaisseaux 05/2004; 97(5):515-21. · 0.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Evaluation of the effect and long-term outcome of accessory pulsatile blood flow versus classical bi-directional cavopulmonary connection (BCPC).
Retrospective review of the medical and surgical records.
Two-hundred and five patients (119 boys, 86 girls) underwent BCPC from 1990 to 1996. Accessory pulsatile flow was present in 68%, flow being maintained through the pulmonary trunc in 46%, systemic-to-pulmonary artery shunt in 13% and mixed in 7%, or patent ductus arteriosus in 2%. Patients with accessory pulsatile flow had lower hospital mortality (3% versus 5%), while mean pulmonary artery pressure (14.1 versus 12.6 mmHg P = 0.050) and increase of oxygen saturation (12.4 versus 8.7, P = 0.034) were significantly higher. The period of artificial ventilation (1.9 day) and ICU stay (6 days) did not differ for both groups. Late mortality was higher following accessory pulsatile flow (6% versus 1%). At late follow-up patients with accessory pulsatile flow had significantly higher oxygen saturation (mean 85 +/- 4%, versus 79 +/- 4%; P < or = 0.005). If subsequent completion of Fontan is considered the optimal palliation and subsequent systemic to pulmonary artery shunt, arteriovenous fistula and transplantation is considered a failure, patients with accessory pulsatile flow had significantly more and earlier completion of the Fontan procedure (mean 1.7 +/- 2.4 years, versus 2.7 +/- 4.4 years; P = 0.008). Survival is not influenced by age at bi-directional cavopulmonary shunt surgery, left or right functional ventricular anatomy or previous palliative surgery. One patient with accessory pulsatile flow developed systemic-to-pulmonary collateral's eventually requiring lobectomy.
Despite two different initial palliative techniques the outcome was not significantly different. Accessory pulsatile blood flow appeared not to be a contra-indication for a completion Fontan procedure. Moreover, the data suggest that after accessory pulsatile flow can safely be performed, at late follow-up oxygen saturation is higher, while, significantly more and earlier completion of Fontan occurred. Age at bi-directional cavopulmonary shunt, basic left or right ventricular anatomy or previous palliative surgery did not influence survival.
European Journal of Cardio-Thoracic Surgery 08/1999; 16(2):104-10. · 2.55 Impact Factor
