A novel nonanticoagulant heparin restores cardiovascular and
hepatocellular function after hemorrhagic shock and decreases
susceptibility to sepsis.
Wang, Ping, Zheng F. Ba, Stephen S. Reich, Main Zhou, Kevin R. Holme,
and Irshad H. Chaudry.
Shock and Trauma Research Institute, Departments of Surgery and
Physiology, Michigan State University,. East Lansing, MI 48824 and
Glycomed Inc., Alameda, CA 94501
APStracts 2:0423H, 1995.
Although heparinization of animals prior to hemorrhage improves cell
and organ function, the potent anticoagulant activity of conventional
heparin precludes its potential clinical use. To determine whether a
novel nonanticoagulant heparin, GM1892, would have any beneficial
effects on cardiovascular and hepatocellular functions and would
decrease susceptibility to sepsis after hemorrhage, laparotomy was
performed on rats (i.e., trauma induced) following which they were
bled to and maintained at a mean arterial pressure of 40 mmHg until
40% of maximal bleedout volume was returned in the form of Ringer's
lactate (RL). The rats were then resuscitated with 3 times the volume
of shed blood with RL over 45 min, followed by infusion of 2 times RL
plus GM1892 (7 mg/kg body wt; 2% the anticoagulant activity of
regular heparin) or saline over 60 min. At 2 and 4 h after the
completion of resuscitation, cardiac output, hepatocellular function,
and microvascular blood flow were determined. The results indicated
that cardiac output, hepatocellular function, and microvascular blood
flow in the liver, spleen, and small intestine decreased
significantly following hemorrhage and resuscitation. Administration
of GM1892, however, restored these parameters. The morphological
abnormality observed after hemorrhage in the liver, kidney, and small
gut was also attenuated with GM1892 treatment. Moreover, GM1892
normalized the elevated plasma PGE2 levels. Sepsis was induced in
additional rats by cecal ligation and puncture (CLP) 20 h after
hemorrhage, and the necrotic cecum was excised 10 h thereafter.
GM1892 treatment significantly decreased mortality after CLP and
cecal excision. Thus, GM1892 appears to be a useful adjunct to fluid
resuscitation since it restores the depressed cardiovascular
responses and decreases susceptibility to sepsis after trauma and
hemorrhage.
Received 21 July 1995; accepted in final form 13 September 1995.
APS Manuscript Number H690-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95