title: C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation.
abstract: Hypotensive resuscitation strategies and inhibition of complement may both be of benefit in hemorrhagic shock. We asked if C5-blocking antibody (anti-C5) could diminish the amount of fluid required and improve responsiveness to resuscitation from hemorrhage. Awake, male Sprague-Dawley rats underwent controlled hemorrhage followed by prolonged (3 h) hypotensive resuscitation with lactated Ringer's or Hextend, with or without anti-C5. Anti-C5 treatment led to an estimated 62.3 and 58.5% reduction in the volume of Hextend and lactated Ringer's, respectively. In the subgroup of animals with a positive mean arterial pressure (MAP) response to fluid infusion following prolonged hypotension, anti-C5 treatment led to an estimated 4.7- and 4.1-fold increase in mean arterial pressure response per unit Hextend and lactated Ringer's infused, respectively. We observed no significant postresuscitation metabolic differences between the anti-C5 groups and controls. Whether anti-C5 could serve as a volume-sparing adjunct that improves responsiveness to fluid administration in humans deserves further study.
authors.affiliation: Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. russell.m.peckham@us.army.mil
authors.forename: Russell M
authors.initials: RM
authors.lastname: Peckham
authors.forename: Michael T
authors.initials: MT
authors.lastname: Handrigan
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Bentley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Falabella
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chrovian
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology; D003182:Complement C5 / Q000276:immunology* / Q000502:physiology; D005440:Fluid Therapy / Q000379:methods*; D007023:Hypotension, Controlled / Q000379:methods*; D007261:Infusions, Intra-Arterial; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*
chemical_list: D000906:Antibodies; D003182:Complement C5; D007552:Isotonic Solutions; D000077325:Ringer's Lactate