Large animal model of chronic pulmonary hypertension.
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.
Sato
Hitoshi
H
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Hall
Candice M
CM
Griffith
Grant W
GW
Johnson
Kent F
KF
McGillicuddy
John W
JW
Bartlett
Robert H
RH
Cook
Keith E
KE
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
D003911:Dextrans; D007202:Indicators and Reagents; C025614:sephadex; D010100:Oxygen