title: Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.
abstract: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure. Intralipid (ILP), a source of parenteral nutrition for patients, contains γ-linolenic acid and soy-derived phytoestrogens that are protective for lungs and heart. We, therefore, investigated the therapeutic potential of ILP in preventing and rescuing monocrotaline-induced PAH and RV dysfunction. PAH was induced in male rats with monocrotaline (60 mg/kg). Rats then received daily ILP (1 mL of 20% ILP per day IP) from day 1 to day 30 for prevention protocol or from day 21 to day 30 for rescue protocol. Other monocrotaline-injected rats were left untreated to develop severe PAH by day 21 or RV failure by approximately day 30. Saline or ILP-treated rats served as controls. Significant increase in RV pressure and decrease in RV ejection fraction in the RV failure group resulted in high mortality. Therapy with ILP resulted in 100% survival and prevented PAH-induced RV failure by preserving RV pressure and RV ejection fraction and preventing RV hypertrophy and lung remodeling. In preexisting severe PAH, ILP attenuated most lung and RV abnormalities. The beneficial effects of ILP in PAH seem to result from the interplay of various factors, among which preservation and/or stimulation of angiogenesis, suppression and/or reversal of inflammation, fibrosis and hypertrophy, in both lung and RV, appear to be major contributors. In conclusion, ILP not only prevents the development of PAH and RV failure but also rescues preexisting severe PAH.
authors: UCLA School of Medicine, Department of Anesthesiology, BH-160CHS, 650 Charles E Young Dr South, Los Angeles, CA 90095-7115, USA.
authors: Soban
authors: S
authors: Umar
authors: Rangarajan D
authors: RD
authors: Nadadur
authors: Jingyuan
authors: J
authors: Li
authors: Federica
authors: F
authors: Maltese
authors: Parisa
authors: P
authors: Partownavid
authors: Arnoud
authors: A
authors: van der Laarse
authors: Mansoureh
authors: M
authors: Eghbali
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004655:Emulsions / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005355:Fibrosis / Q000517:prevention & control; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D016686:Monocrotaline; D009206:Myocardium / Q000473:pathology; D010743:Phospholipids / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C545823:soybean oil, phospholipid emulsion; D016686:Monocrotaline; D013024:Soybean Oil; D053148:Caspase 3