Showing papers by "Lewis J. Rubin published in 2003"
TL;DR: Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.
374 citations
TL;DR: Long-term treatment with bosentan is safe and has sustained benefits on exercise capacity and hemodynamics in patients with PAH and was associated with an improvement in hemodynamic parameters and modified NYHA functional class.
292 citations
TL;DR: The results suggest that the antiproliferative effect of BMPs is partially due to induction of PASMC apoptosis, which serves as a critical mechanism to maintain normal cell number in the pulmonary vasculature.
Abstract: Pulmonary vascular medial hypertrophy in primary pulmonary hypertension (PPH) is mainly caused by increased proliferation and decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Mutations of the bone morphogenetic protein (BMP) receptor type II (BMP-RII) gene have been implicated in patients with familial and sporadic PPH. The objective of this study was to elucidate the apoptotic effects of BMPs on normal human PASMCs and to examine whether BMP-induced effects are altered in PASMCs from PPH patients. Using RT-PCR, we detected six isoforms of BMPs (BMP-1 through -6) and three subunits of BMP receptors (BMP-RIa, -RIb, and -RII) in PASMCs. Treatment of normal PASMCs with BMP-2 or -7 (100-200 nM, 24-48 h) markedly increased the percentage of cells undergoing apoptosis. The BMP-2-mediated apoptosis in normal PASMCs was associated with a transient activation or phosphorylation of Smad1 and a marked downregulation of the antiapoptotic protein Bcl-2. In PASMCs from PPH patients, the BMP-2- or BMP-7-induced apoptosis was significantly inhibited compared with PASMCs from patients with secondary pulmonary hypertension. These results suggest that the antiproliferative effect of BMPs is partially due to induction of PASMC apoptosis, which serves as a critical mechanism to maintain normal cell number in the pulmonary vasculature. Inhibition of BMP-induced PASMC apoptosis in PPH patients may play an important role in the development of pulmonary vascular medial hypertrophy in these patients.
257 citations
Rush University Medical Center1, University College Dublin2, Johns Hopkins University3, Columbia University4, University of California, Los Angeles5, University of Alabama6, Houston Methodist Hospital7, Veterans Health Administration8, Duke University9, Mayo Clinic10, University of Colorado Denver11, University of California, San Diego12
TL;DR: Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term and can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system.
Abstract: Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension, but it requires intravenous infusion and is associated with adverse effects. The objective of this study was to evaluate the effects of an epoprostenol analog, treprostinil, for management of pulmonary hypertension. Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials. In the first trial, intravenous epoprostenol and intravenous treprostinil were compared. In the second trial, intravenous treprostinil and subcutaneous treprostinil were compared. In the third trial, subcutaneous treprostinil was compared with placebo infusion during an 8-week period. Intravenous epoprostenol and intravenous treprostinil resulted in a similar reduction in pulmonary vascular resistance acutely (22% and 20%, respectively). Intravenous treprostinil and subcutaneous treprostinil also demonstrated comparable short-term decrease in pulmonary vascular resistance (23% and 28%, respectively). The placebo-controlled 8-week trial demonstrated a mean improvement of 37 +/- 17 m as measured by the 6-minute walk distance in patients receiving treprostinil compared with a 6 +/- 28 m reduction in those receiving placebo. There were trends toward an improvement in cardiac index and pulmonary vascular resistance index in the treprostinil group. Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term. Treprostinil can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system.
226 citations
TL;DR: It is concluded that elevated plasma FVIII is the first prothrombotic factor identified in a large proportion of CTEPH patients.
Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is an enigmatic disorder lacking signs, symptoms and classical risk factors for venous thromboembolism. The objective of the prospective case controlled study, carried out at the Pulmonary Hypertension Unit, University Hospital Vienna, Austria, was to investigate whether plasma FVIII is ele-vated in CTEPH patients. The study examined 122 consecutive patients diagnosed with CTEPH. Plasma FVIII was measured and compared with plasma FVIII of healthy controls (n=82) and of patients with non-thromboembolic pulmonary arterial hypertension (PAH, n=88).Results show that CTEPH patients had higher FVIII levels than controls (233±83IU/dl versus 123±40IU/dl, p
217 citations
TL;DR: Epoprostenol may sufficiently reverse the pathogenic process in select patients with PAH to allow a transition to less complex and less invasive treatment modalities.
48 citations
42 citations
19 citations