title: The evolution of isolated bilateral lung contusion from blunt chest trauma in rats: cellular and cytokine responses.
abstract: Lung contusion is the leading cause of death from blunt thoracic trauma in adults, but its mechanistic pathophysiology remains unclear. This study uses a recently developed rat model to investigate the evolution of inflammation and injury in isolated lung contusion. Bilateral lung contusion with minimal cardiac trauma was induced in 54 anesthetized rats by dropping a 0.3-kg hollow cylindrical weight onto a precordial shield (impact energy, 2.45 Joules). Arterial oxygenation, pressure-volume (P-V) mechanics, histology, and levels of erythrocytes, leukocytes, albumin, and inflammatory mediators in bronchoalveolar lavage (BAL) were assessed at 8 min, at 4, 12, 24, and 48 h, and at 7 days after injury. The role of neutrophils in the evolution of inflammatory injury was also specifically studied by depleting these cells with intravenous vinblastine before lung contusion. Arterial oxygenation was severely reduced at 8 min to 24 h postcontusion, but became almost normal by 48 h. Levels of erythrocytes, leukocytes, and albumin in BAL were increased at <or=24 h, and returned toward normal by 48 h. Deficits in P-V mechanics were most apparent at 24 h postcontusion. Levels of macrophage inflammatory polypeptide-2, cytokine-induced neutrophil chemoattractant-1, and interleukin 6 in BAL peaked at 24 h, whereas monocyte chemoattractant protein-1 and interleukin 1beta peaked at 24 to 48 h postcontusion. Histology showed early hemorrhagic injury (8 min-12 h), with neutrophilic infiltration at 24 h and areas of bronchiolitis obliterans organizing pneumonia-associated fibrosis at 7 days. Vinblastine-treated neutropenic rats had significantly reduced lung injury based on total lung volume at 4 h and on BAL albumin levels at 24 h postcontusion. Inflammatory injury from isolated bilateral lung contusion in rats is most severe in the acute period (8 min-24 h) after initial blunt trauma, and includes a component of neutrophil-dependent pathology.
authors.affiliation: Department of Surgery, State University of New York, Buffalo 14215, USA. kraghave@ecmc.edu
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavendran
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: James A
authors.initials: JA
authors.lastname: Woytash
authors.forename: Jadwiga D
authors.initials: JD
authors.lastname: Helinski
authors.forename: Cristi J
authors.initials: CJ
authors.lastname: Marschke
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Manderscheid
authors.forename: Robert H
authors.initials: RH
authors.lastname: Notter
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001989:Bronchiolitis Obliterans / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D018932:Chemokine CCL2 / Q000378:metabolism; D054412:Chemokine CCL8; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000378:metabolism; D003288:Contusions / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D006470:Hemorrhage / Q000473:pathology; D000860:Hypoxia; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D015846:Monokines / Q000378:metabolism; D009503:Neutropenia / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism; D011312:Pressure; D051381:Rats; D013898:Thoracic Injuries / Q000378:metabolism*; D013997:Time Factors; D014747:Vinblastine / Q000494:pharmacology; D014949:Wounds, Nonpenetrating
chemical_list: D000418:Albumins; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines; D014747:Vinblastine; D010100:Oxygen