Pathologic regression of primary pulmonary hypertension in left native lung following right single-lung transplantation

Levy, N; Liapis, Helen; Eisenberg, P.R.; Botney, Mitchell D.; Trulock, Elbert P.

doi:10.1016/s1053-2498(00)00153-4

Cited by 32 publications

(25 citation statements)

References 9 publications

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“…28 Another report described a patient who manifested pathological regression of IPAH in the native lung after single-lung transplantation of the contralateral lung. 29 The pulmonary vascular changes in the native lung showed regression compared with the characteristic findings of IPAH in the lung explant obtained previously. This report supports the hypothesis that hemodynamic alterations with normalization of pressure and blood flow preferentially directed to the transplanted lung may result in regression of the vascular changes of the native lung.…”

Section: Discussionsupporting

confidence: 51%

Prednisolone Inhibits Proliferation of Cultured Pulmonary Artery Smooth Muscle Cells of Patients With Idiopathic Pulmonary Arterial Hypertension

et al. 2005

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Background-Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH. Methods and Results-Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor (PDGF), PSL was added at different concentrations and cell proliferation was assessed by 3 H-thymidine incorporation. PSL (2ϫ10 Ϫ4 and 2ϫ10

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Section: Discussionsupporting

confidence: 51%

Prednisolone Inhibits Proliferation of Cultured Pulmonary Artery Smooth Muscle Cells of Patients With Idiopathic Pulmonary Arterial Hypertension

et al. 2005

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“…Prednisolone is also routinely used postoperatively in patients with IPAH who have undergone lung transplantation (24, 42). The use of immunosuppressants to treat pulmonary hypertension has shown promising beneficial effects in some patients (4,19). In addition to its immunosuppressive effects, prednisolone has been shown to inhibit PDGF-stimulated proliferation of pulmonary artery smooth muscle cells (PASMC) from patients with IPAH (26).…”

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confidence: 99%

Prednisolone inhibits PDGF-induced nuclear translocation of NF-κB in human pulmonary artery smooth muscle cells

Ogawa¹,

Firth²,

Yao³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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inhibits PDGF-induced nuclear translocation of NF-B in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 295: L648 -L657, 2008. First published August 15, 2008 doi:10.1152/ajplung.90245.2008.-Pulmonary vascular remodeling, a major cause for the elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension (PAH), is partially due to increased proliferation of pulmonary arterial smooth muscle cells (PASMC) in the media, resulting in vascular wall thickening. Plateletderived growth factor (PDGF) is a potent mitogen that may be involved in the progression of PAH. Blockade of PDGF receptors has been demonstrated to have therapeutic potential for patients with severe pulmonary hypertension. Prednisolone is an immunosuppressant shown to have anti-inflammatory and antiproliferative effects on PASMC. This study was designed to investigate whether PDGF and prednisolone affect human PASMC proliferation by regulating the nuclear translocation of NF-B (a transcription factor composed of 2 subunits, p50 and p65). Treatment of human PASMC with PDGF (10 ng/ml) significantly increased nuclear translocation of p50 and p65 subunits. Inhibition of NF-B activation or nuclear translocation of p50/p65 significantly attenuated PDGF-induced PASMC proliferation (determined by [ 3 H]thymidine incorporation). In the presence of prednisolone (200 M), the PDGF-induced nuclear translocation of p50 and p65 subunits was markedly inhibited (P Ͻ 0.05 vs. the cells treated with PDGF alone). These results indicate that PDGF-induced nuclear translocation of NF-B may play an important role in stimulating PASMC proliferation (and/or enhancing PASMC survival), whereas prednisolone may exert anti-inflammatory and antiproliferative effects on PASMC by inhibiting NF-B nuclear translocation. proliferation; pulmonary arterial hypertension; immunosuppressant; therapy PULMONARY VASCULAR REMODELING is a major contributor to the elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension. Increased growth factors (e.g., PDGF) and enhanced inflammatory responses (characterized with cytokines and chemokines that can stimulate or activate NF-B) have recently been demonstrated to be important causes for the development of pulmonary vascular remodeling in patients with idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (26,29). Prednisolone is an anti-inflammatory and immunosuppressive drug widely used for treatment of bronchial asthma, chronic obstructive pulmonary disease, autoimmune disease, and leukemia (2,6,17,23,28). Prednisolone is also routinely used postoperatively in patients with IPAH who have undergone lung transplantation (24, 42). The use of immunosuppressants to treat pulmonary hypertension has shown promising beneficial effects in some patients (4,19). In addition to its immunosuppressive effects, prednisolone has been shown to inhibit PDGF-stimulated proliferation of pulmonary artery smooth muscle cells (PASMC) from p...

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“…Even though high-dose IV epoprostenol strongly inhibits the vasoconstriction and cell-proliferation of pulmonary vessels, it appears to be difficult to prevent the progression of pulmonary vascular remodeling without adequate reduction of pulmonary arterial pressure. 7) It has been proposed that maintaining PAP and PVR at low levels may be essential for reverse remodeling, 8,9) but on the other hand, it seems almost impossible to restore normal hemodynamics with monotherapy using one of oral prostacyclin analogues, ERA, and PDE-5 inhibitors in IPAH patients. 10) Thus, initial and aggressive combination therapy whose aim is to obtain normal hemodynamics should be attempted and may achieve reverse remodeling.…”

Section: Discussionmentioning

confidence: 99%

Initial and Programmed Combination Therapy With Oral Drugs for Severe Idiopathic Pulmonary Arterial Hypertension

et al. 2011

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SummaryA 49-year-old woman suffering from rapidly progressing right-sided heart failure assessed as World Health Organization functional class (WHO-FC) IV is described. After treatment with oxygen and diuretics, she was in WHO-FC III on admission to our hospital, as confirmed by her poor exercise tolerance in cardiopulmonary exercise testing. Upon detailed examination, she was diagnosed as having idiopathic pulmonary arterial hypertension (IPAH). Right heart catheterization (RHC) revealed severe pulmonary hypertension (mPAP = 65 mmHg) with a markedly decreased cardiac index (CI = 1.0 L/minute/m 2 ), and an acute vasoreactivity test with nitric oxide inhalation did not show any response. Due to her severe condition, we decided to attempt oral combination therapy consisting of bosentan, tadalafil, and beraprost, prescribed in the same order and titrated up to their maximum respective doses, instead of intravenous (IV) epoprostenol therapy. Her clinical symptoms improved day by day, and the hemodynamic parameters recovered to nearly normal ranges about 6 months after initiation of the combination therapy. Initial/programmed oral combination therapy for severe IPAH patients is not yet fully established, and there is less evidence concerning its efficacy than IV epoprostenol therapy. However, it has tremendous advantages for PAH patients when they respond well. It is very important to further identify what types of PAH patients will respond to this oral combination therapy and should be treated with it as the first-line therapy. (Int Heart J 2011; 52: 323-326)

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Pathologic regression of primary pulmonary hypertension in left native lung following right single-lung transplantation

Cited by 32 publications

References 9 publications

Prednisolone Inhibits Proliferation of Cultured Pulmonary Artery Smooth Muscle Cells of Patients With Idiopathic Pulmonary Arterial Hypertension

Prednisolone Inhibits Proliferation of Cultured Pulmonary Artery Smooth Muscle Cells of Patients With Idiopathic Pulmonary Arterial Hypertension

Prednisolone inhibits PDGF-induced nuclear translocation of NF-κB in human pulmonary artery smooth muscle cells

Initial and Programmed Combination Therapy With Oral Drugs for Severe Idiopathic Pulmonary Arterial Hypertension

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