title: Prostacyclin therapy increases right ventricular capillarisation in a model for flow-associated pulmonary hypertension.
abstract: Pulmonary hypertension, and consequently right ventricular failure, complicates several congenital heart defects. Although intervention in the prostacyclin-thromboxane ratio is known to improve outcome, the underlying mechanism is not clear. Therefore, effects of acetyl salicylic acid and iloprost are studied in an animal model for flow-associated pulmonary hypertension. Male Wistar rats with flow-associated pulmonary hypertension, an aortocaval shunt in addition to monocrotaline induced pulmonary hypertension, were treated with low-dose aspirin (25 mg/kg/day) or iloprost (72 microg/kg/day). Effects on pulmonary hemodynamics and pulmonary vascular remodeling as well as right ventricular hemodynamics and remodeling were evaluated. Ninety percent (n=7/8) of the untreated pulmonary hypertensive rats developed dyspnea and pleural fluid, whereas this was seen in 50% (n=4/8, ns) and 10% (n=1/8, P<0.05 vs. untreated animals) of the aspirin and iloprost-treated rats, respectively. This could not be attributed to changes in pulmonary artery pressure, wall-lumen ratio of the pulmonary vasculature or right ventricular hypertrophy. However, both therapies restored reduced right ventricular capillary to myocyte ratio in pulmonary hypertensive rats (0.95+/-0.10 in untreated rats vs. 1.38+/-0.18 in control animals; P<0.05, and 1.32+/-0.11 in aspirin-treated and 1.29+/-0.9 in iloprost-treated rats; both P<0.05 vs. non-treated animals), which was associated with improved right ventricular contractility (iloprost). Thus, interventions in the prostacyclin-thromboxane metabolism improve outcome in rats with flow-associated pulmonary hypertension. However, these effects may be attributed to effects on cardiac rather than on pulmonary vascular remodeling.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. m.e.van.albada@med.umcg.nl
authors.forename: Mirjam E
authors.initials: ME
authors.lastname: van Albada
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
authors.forename: Marnix
authors.initials: M
authors.lastname: Niggebrugge
authors.forename: Richard
authors.initials: R
authors.lastname: van Veghel
authors.forename: Adri H
authors.initials: AH
authors.lastname: Cromme-Dijkhuis
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016285:Iloprost / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D010975:Platelet Aggregation Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016718:Arachidonic Acid; D040262:Receptors, Vascular Endothelial Growth Factor; D016285:Iloprost; D001241:Aspirin