title: Large animal model of chronic pulmonary hypertension.
abstract: A large animal model is needed to study artificial lung attachment in a setting simulating chronic lung disease with significant pulmonary hypertension (PH). This study sought to create a sheep model that develops significant PH within 60 days with a low rate of mortality. Sephadex beads were injected in the pulmonary circulation of sheep every other day for 60 days at doses of 0.5, 0.75, and 1 g (n = 10, 10, 7). Mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were obtained every 2 weeks. In the 0.5, 0.75, and 1-g groups, 90, 70, and 14.3% of sheep completed the study, respectively, with the remainder experiencing heart failure. By the 60th day, pulmonary vascular resistance had increased (p < 0.01) from 0.89 +/- 0.3 to 3.2 +/- 0.9 mm Hg/(L/min) and from 0.9 +/- 0.3 to 4.3 +/- 3.2 mm Hg/(L/min) in the 0.5 and 0.75-g groups, respectively. Significant right ventricular hypertrophy was observed in the 0.75-g group but not in the 0.5-g group. Data from the 1-g group were insufficient for analysis due to high mortality. Thus, the 0.5 and 0.75-g groups generate significant PH, but the 0.75-g group is a better model of chronic PH in lung disease due to the development of right ventricular hypertrophy.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sato
authors.forename: Candice M
authors.initials: CM
authors.lastname: Hall
authors.forename: Grant W
authors.initials: GW
authors.lastname: Griffith
authors.forename: Kent F
authors.initials: KF
authors.lastname: Johnson
authors.forename: John W
authors.initials: JW
authors.lastname: McGillicuddy
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.forename: Keith E
authors.initials: KE
authors.lastname: Cook
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D002908:Chronic Disease; D003911:Dextrans / Q000633:toxicity; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D007202:Indicators and Reagents / Q000633:toxicity; D010100:Oxygen / Q000378:metabolism; D012756:Sheep; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D003911:Dextrans; D007202:Indicators and Reagents; C025614:sephadex; D010100:Oxygen