Neutrophil accumulations due to pulmonary thromboxane synthesis mediate acid aspiration injury.
Acid aspiration leads to lung injury associated with high levels of plasma thromboxane (Tx). This study tests the role of Tx synthesis by the aspirated lung segment in mediating local and remote neutrophil (PMN) sequestration, alveolar diapedesis, and permeability edema. Anesthetized rats underwent tracheostomy and insertion of a fine-bore cannula into the anterior segment of the left lung. This was followed by the installation of either 0.1 ml saline (n = 18) or the Tx synthase inhibitor OKY 046 (0.1 mg/kg in 0.1 ml, n = 18). Twenty minutes later either 0.1 ml 0.1 N HCL or 0.1 ml saline was similarly introduced (n = 18). Three hours later, in the saline-HCl group, the rise in Tx concentration in both plasma (1,340 pg/ml) and bronchoalveolar lavage (BAL) fluid (2,100 pg/ml) was higher than that in the saline-saline aspirated control group (350 and 115 pg/ml, respectively; both P less than 0.05). In the acid-aspirated lung PMN sequestration [87 PMN/10 high-power fields (HPF)] and diapedesis (96 x 10(4) PMN/ml in BAL) were higher than control values of 7 PMN/10 HPF and 3 x 10(4) PMN/ml (both P less than 0.05). Acid aspiration induced local permeability edema with a high protein concentration in BAL of 3,350 micrograms/ml and an increase in lung wet-to-dry weight ratio (W/D) of 6.6, both higher than control values of 482 micrograms/ml and 3.4, respectively (P less than 0.05). Leukosequestration in the aspirated side started at 30 min and was progressive over a 3-h monitoring period.(ABSTRACT TRUNCATED AT 250 WORDS)
Goldman
G
G
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Welbourn
R
R
Klausner
J M
JM
Kobzik
L
L
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006851:Hydrochloric Acid; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000096:biosynthesis*
D013928:Thromboxane A2; D006851:Hydrochloric Acid