Continuous air embolization into sheep causes sustained pulmonary hypertension and increased pulmonary vasoreactivity.
Baseline pulmonary arterial, left atrial and systemic artery pressures, cardiac output, and lung lymph flow were measured in seven chronically catheterized sheep before continuous air embolization into the pulmonary artery, which caused a two-to-threefold increase in pulmonary vascular resistance (PVR) for 12 days. Air embolization was discontinued on days 4, 8, and 12 and hemodynamic measurements were repeated. Thromboxane B2, 6-keto-PGF1 alpha, and protein were measured in lung lymph and blood plasma on days 0, 4, 8 and 12. Air embolization caused an acute, sustained rise in pulmonary artery pressure and PVR (baseline, 3.68 +/- 0.21; air, 8.32 +/- 0.62, mean +/- SE). By day 4, PVR was increased significantly even when air flow was interrupted (5.97 +/- 0.72) and by day 12, it was almost twice baseline; pulmonary artery pressure also remained elevated (baseline, 19 +/- 1 cm H2O; day 12, 31 +/- 3). Pulmonary vasoreactivity to PGH2-A was significantly increased on days 4, 8, and 12 (day 12, 285 +/- 41% of baseline response). Lung lymph flow, protein, and thromboxane clearance were increased throughout the study while clearance of 6-keto-PGF1 alpha was increased at day 4 and falling by day 8. At autopsy, morphometric analysis of the barium-injected pulmonary arterial bed revealed striking structural remodeling, extension of muscle into smaller arteries than normal: decreased peripheral arterial filling, increased medial thickness, and dilated large pulmonary arteries. Continuous air embolization into sheep causes the structural and functional changes of chronic pulmonary hypertension accompanied by increased pulmonary vasoreactivity to a bolus of PGH2-A. The abrupt onset of the sustained elevation in PVR induced by air embolization may account for the severity of the structural remodelling, particularly for the increased medial thickness.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
E A
EA
Perkett
K L
KL
Brigham
B
B
Meyrick
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D004195:Disease Models, Animal; D004618:Embolism, Air; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008198:Lymph Nodes / Q000503:physiopathology; D011651:Pulmonary Artery / Q000473:pathology* / Q000503:physiopathology; D012756:Sheep; D014655:Vascular Resistance