Chemically modified heparin improves hepatocellular function, cardiac output, and microcirculation after trauma-hemorrhage and resuscitation.
BACKGROUND
Although heparinization before hemorrhagic shock improves tissue perfusion and organ function, the anticoagulant properties of conventional heparin preclude its clinical use. The purpose of this study was to determine whether chemically modified heparin (CMH), which does not have any significant anticoagulant activity, produces any beneficial effects on hepatocellular and cardiovascular function and microcirculation after trauma-hemorrhage and resuscitation.


METHODS
After induction of tissue trauma (that is, laparotomy), rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with three times the volume of shed blood with RL over 45 minutes, followed by two times RL and CMH (7 mg/kg body wt; approximately 10% of the anticoagulant activity of conventional heparin), conventional heparin (7 mg/kg), or normal saline solution over 60 minutes. Hepatocellular function, cardiac output, and microvascular blood flow were determined thereafter.


RESULTS
The results indicate that hepatocellular function, cardiac output, and microvascular blood flow in the liver, kidney, spleen, and small intestine decreased markedly after trauma-hemorrhage and resuscitation. Infusion of CMH or conventional heparin during resuscitation, however, restored or significantly improved the mentioned parameters.


CONCLUSIONS
Because CMH does not have any significant anticoagulant properties and because it restores or significantly improves hepatocellular function, cardiac output, and tissue perfusion, this agent appears to be a useful adjunct in the treatment of trauma and hemorrhagic shock, even in the absence of blood resuscitation.
Wang
P
P
Department of Surgery, Michigan State University, East Lansing 48824-1315.
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Z F
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Chaudry
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D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000503:physiopathology*; D006493:Heparin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation; D014947:Wounds and Injuries / Q000503:physiopathology*
D006493:Heparin