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Complement partially mediates acid aspiration‐induced remote organ injury in the rat
Author(s) -
YAMADA H.,
KUDOH I.,
NISHIZAWA H.,
KANEKO K.,
MIYAZAKI H.,
OHARA M.,
OKUMURA F.
Publication year - 1997
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.1997.tb04771.x
Subject(s) - medicine , bronchoalveolar lavage , lung , myeloperoxidase , cannula , pulmonary edema , pharmacology , tumor necrosis factor alpha , edema , pathology , anesthesia , immunology , inflammation , surgery
Background: Acid aspiration into one lung is known to cause both a local as well as remote organ injury characterized by neutrophil sequestration and subsequent edema. This study investigated the role of the complement cascade in the development of acid aspiration‐induced local lung and remote organ injuries using K‐76 COONa (K76), an anticomplement agent that inhibits the complement pathway at the C5 step, and its usefulness as a treatment drug. Methods: Anesthetized rats underwent tracheostomy and insertion of a cannula. K76 was intraperitoneally administrated prior to or immediately after the instillation of 0.1 ml of HC1 (0.1N) or phosphate buffer solution (PBS) into the left lung. Inflammatory responses were evaluated by tumor necrosis factor a (TNFa) in the plasma and the bronchoalveolar lavage fluid (BALF) (n=4), tissue myeloperoxidase (MPO), wet‐to‐dry weight ratio (W/D ratio)(n=6), and protein concentration in the BALF (n=6). Results: Acid instillation caused an increase in the plasma TNFa, which was significantly attenuated by the administration of K76 prior to or after the acid instillation. Acid instillation to the left lung resulted in an increase of MPO and W/D ratios of the left lung, the right lung, and the small intestine. The administration of K76 inhibited the increase of MPO in these organs. K76 inhibited the increase of W/D ratios of the right non‐in‐stillated lung and the small intestine. Acid instillation led to increased protein concentration in the BALF of the left lung, which was not inhibited by K76. K76 administrated after the acid instillation had the same effects. TNFa in the BALF was not detected in all groups. Conclusion: These results suggest that localized acid aspiration induces, through the C5a step of the complement system‐dependent mechanisms, TNFa formation and neutrophil sequestration, which caused the increase of endothelial permeability of the systemic organs. K76 is effective as a treatment drug in modulating some of the injuries caused by the acid instillation, but further investigation is warranted as to its potential as a therapeutic agent.