C1-esterase-inhibitor treatment at early reperfusion of hemorrhagic shock reduces mesentry leukocyte adhesion and rolling.
OBJECTIVE
Complement activation probably plays a pathogenic role in multiple organ failure in shock. This study evaluates the effects of C1-esterase-inhibitor treatment on leukocyte-endothelial interaction in the mesenteric microcirculation in hemorrhagic shock.


METHODS
Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body wt. for 60 minutes) followed by a 4-hour reperfusion period. C1-INH (100 IU/kg body wt. i.v.) or 0.9% NaCl i.v. were administered as a bolus at the beginning of reperfusion. Reperfusion time mimicked a "pre-hospital" phase of 30 minutes followed by a quasi "in-hospital" phase of 3.5 hours. The "in-hospital" phase was initiated by substitution of blood followed by fluid resuscitation with normal saline.


RESULTS
Application of C1-INH markedly reduced rolling and adherent leukocytes to numbers approaching baseline values. Vmax and shear rate of the mesenteric microcirculation improved in both groups after reperfusion with a trend to higher values in the C1-INH group (n.s. p = 0.08).


CONCLUSIONS
C1-INH applied in a bolus dose of 100 IU/kg body wt. i.v. abrogated enhanced leukocyte adhesion and rolling in the mesenteric microcirculation after hemorrhagic shock. Single bolus treatment with a complement inhibitor may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.
Horstick
G
G
2nd Medical Clinic, Johannes Gutenberg-University Mainz, Germany.horstick@mail.uni-mainz.de
Kempf
T
T
Lauterbach
M
M
Bhakdi
S
S
Kopacz
L
L
Heimann
A
A
Malzahn
M
M
Horstick
M
M
Meyer
J
J
Kempski
O
O
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000166:cytology*; D006439:Hemodynamics / Q000187:drug effects; D007082:Ileum / Q000098:blood supply; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D013152:Splanchnic Circulation / Q000187:drug effects
D003174:Complement C1 Inactivator Proteins