title: Microthrombus formation may trigger lung injury after acute blood loss.
abstract: We showed previously that acute blood loss, without resuscitation, caused marked maldistribution of interalveolar perfusion. Because hemorrhage is a known risk factor for the development of lung injury, the goal of our present studies was to determine if there was a correlation between perfusion maldistribution and the subsequent development of lung injury after blood loss. Specifically, we wanted to know if the perfusion maldistribution might be due to microthrombus formation and/or leukocyte sequestration within the pulmonary microcirculation. We bled rats (30% blood loss) and harvested their lungs 45 min or 24 h later. Lungs were prepared for perfusion distribution analysis, Western blot analysis to measure whole-lung fibrinogen concentrations, and for immunohistochemistry to measure fibrin deposition and leukocyte deposition (CD16 fluorescence). Perfusion was significantly maldistributed at 45 min and 24 h (P < 0.05). At 45 min, whole-lung fibrinogen concentrations were less than half that in controls (P < 0.05), whereas numbers of fibrin microthrombi were 2.5-fold greater than control by 45 min (not statistically significant) and were 4.5-fold greater by 24 h (P = 0.01). Leukocyte deposition was two-fold greater than control by 45 min (not statistically significant) and was 4-fold greater by 24 h (P = 0.02). Fibrin-to-leukocyte nearest-neighbor distances remained unchanged (18.1 [SD, 1.1] μm) even as the numbers of both increased with time after blood loss. Our results suggest that soluble fibrinogen polymerized to insoluble fibrin within minutes after acute blood loss, which caused perfusion maldistribution and attracted leukocytes. The development of lung injury after blood loss may be a consequence of leukocyte chemoattraction to fibrin microthrombi that seem to form within minutes after blood loss.
authors.affiliation: Dpartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. conhaim@surgery.wisc.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Conhaim
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Mangino
authors.forename: William F
authors.initials: WF
authors.lastname: Dovi
authors.forename: Kal E
authors.initials: KE
authors.lastname: Watson
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Warner
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Harms
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D005260:Female; D006470:Hemorrhage / Q000150:complications* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000150:complications* / Q000378:metabolism