Submitted on August 21, 2006
Accepted on October 12, 2006
C5-Blocking Antibody Reduces Fluid Requirements and Improves Responsiveness to Fluid Infusion in Hemorrhagic Shock Managed with Hypotensive Resuscitation
Russell M Peckham1*, Michael T Handrigan2, Timothy B. Bentley2, Michael J. Falabella2, Andrew D. Chrovian2, Gregory L. Stahl3, and George C Tsokos4
1 Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States; Dept. of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States
2 Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
3 Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
4 Dept. of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States; Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
* To whom correspondence should be addressed. E-mail: russell.m.peckham{at}us.army.mil.
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 (3h) hypotensive resuscitation with Lactated Ringer's (LR) or Hextend (Hex), with or without anti-C5. Anti-C5 treatment led to an estimated 62.3% and 58.5% reduction in the volume of Hex and LR, 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 fold and 4.1 fold increase in MAP response per unit Hex and LR infused, respectively. We observed no significant post-resuscitation 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.
