Specific neutrophil elastase inhibitor does not attenuate acute lung injury induced by air embolism in awake sheep.
To investigate the role played by neutrophil-derived elastase in acute lung injury, this study examined the effects of treatment of ONO-5046, a competitive, reversible, and specific neutrophil elastase inhibitor, on lung dysfunction induced by air emboli in awake sheep. Sheep were prepared with chronic lung lymph fistula. In experiment 1, air (1.23 mL/min) was infused over a 2-h period into the pulmonary artery and hemodynamic monitoring was performed over a 5-h period. In experiment 2, air was infused in the same manner as in experiment 1, 1 h after the continuous infusion of ONO-5046 (10 mg/kg h-1) had begun. In experiment 1, pulmonary artery pressure (Ppa) increased from the baseline value of 17.0 +/- 0.7 cm H2O to 28.3 +/- 1.8 1 h after the beginning of the air infusion. Ppa returned to the baseline values within 1 h after the air infusion was stopped. Lung lymph flow (Qlym) increased from the baseline value of 3.7 +/- 0.7 mL/0.5 h to 8.5 +/- 1.9 after 1 h of air infusion. After the air infusion was stopped, Qlym continued to increase. When sheep were treated with ONO-5046, Ppa and Qlym increased in a fashion similar to that in the experiment 1. These findings suggest that ONO-5046 does not attenuate air embolism-induced lung injury and that neutrophil-derived elastase may not play an important role in air embolism-induced lung injury in awake sheep.
Miyahara
T
T
1st Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto City, Japan.
Kubo
K
K
Koizumi
T
T
Kobayashi
T
T
Sekiguchi
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000818:Animals; D001826:Body Fluids / Q000502:physiology; D002908:Chronic Disease; D003243:Consciousness; D004618:Embolism, Air / Q000150:complications* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005402:Fistula / Q000150:complications; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D007962:Leukocytes / Q000166:cytology; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism; D008206:Lymphatic Diseases / Q000150:complications; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011652:Pulmonary Circulation / Q000187:drug effects; D012680:Sensitivity and Specificity; D012756:Sheep; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism
D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C069195:sivelestat; D019272:Leukocyte Elastase; D010100:Oxygen; D005998:Glycine