A novel nonanticoagulant heparin improves splenocyte and peritoneal macrophage immune function after trauma-hemorrhage and resuscitation.
Recent studies have shown that heparinization of animals prior to or even after hemorrhagic shock improves tissue perfusion and organ function. However, the anticoagulant properties of conventional heparin preclude its clinical use in trauma care. The aim of our study, therefore, was to determine whether chemically modified heparin, i.e., a novel nonanticoagulant heparin (GM1892), which does not have significant anticoagulant activity (approximately 2% of the anticoagulant activity of conventional heparin), produces any beneficial effects on splenocyte and macrophage immune function following trauma-hemorrhage and resuscitation. To determine this, following the induction of tissue trauma (i.e., a midline laparotomy), mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 1 hr. The animals then received GM1892 (7 mg/kg body wt), conventional heparin (7 mg/kg body wt), normal saline prior to resuscitation with three times the volume of shed blood with Ringer's lactate. Two hours after resuscitation the animals were sacrificed, splenocytes were isolated, and splenic, as well as peritoneal macrophage, cultures were established. The ability of the splenocytes to release IL-2 and IL-3 in response to mitogen was markedly improved in hemorrhaged animals which were treated with GM1892 or conventional heparin compared to saline-treated mice. Furthermore, the capacity of splenic and peritoneal macrophages to release IL-6 was restored in the hemorrhaged animals that received GM1892 or conventional heparin.(ABSTRACT TRUNCATED AT 250 WORDS)
Zellweger
R
R
Department of Surgery, Michigan State University, East Lansing 48824, USA.
Ayala
A
A
Zhu
X L
XL
Holme
K R
KR
DeMaso
C M
CM
Chaudry
I H
IH
D000818:Animals; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006470:Hemorrhage / Q000276:immunology*; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000031:analogs & derivatives* / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D012151:Resuscitation; D013154:Spleen / Q000166:cytology; D014947:Wounds and Injuries / Q000276:immunology*
D016207:Cytokines; D006495:Heparin, Low-Molecular-Weight; D007378:Interleukins; C094917:GM 1892; D006493:Heparin