Cellular mechanisms of heparinase III protection in rat traumatic shock.
Pentobarbital-anesthetized rats subjected to traumatic shock developed a shock state characterized by marked hypotension to 65-70 mmHg, a survival time of 88 +/- 13 min, significant increases in ileal myeloperoxidase activity (P < 0.01), and severe endothelial dysfunction as evidenced by a significant (P < 0.01) decrease in vasorelaxation to endothelium-dependent dilators. Treatment with heparinase III (45 microg . kg-1 . min-1) 10 min posttrauma prolonged survival time to 223 +/- 19 min (P < 0.001), significantly attenuated ileal myeloperoxidase activity (P < 0.01), and significantly preserved endothelial function (P < 0.05). Intravital microscopy of the rat mesentery showed that infusion of heparinase III (45-67 microg . kg-1 . min-1) significantly (P < 0.01) attenuated both leukocyte rolling and adherence in the rat mesenteric microvasculature in response to NG-nitro-L-arginine methyl ester stimulation. Immunohistochemical localization of surface-expressed P-selectin on mesenteric venules showed that heparinase III infusion at 45-67 microg . kg-1 . min-1 significantly (P < 0.05) attenuated the increase in surface P-selectin expression. The beneficial effects of heparinase III are mediated at least in part by attenuating leukocyte-endothelial cell interactions via a P-selectin-dependent mechanism.
Hayward
R
R
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Scalia
R
R
Hopper
B
B
Appel
J Z
JZ
Lefer
A M
AM
D000768:Anesthesia, General; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007022:Hypotension / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D007082:Ileum; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019007:P-Selectin / Q000096:biosynthesis; D010424:Pentobarbital; D009195:Peroxidase / Q000032:analysis; D011133:Polysaccharide-Lyases / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012774:Shock, Traumatic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D015996:Survival Rate; D013997:Time Factors; D014699:Venules / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D019007:P-Selectin; D009195:Peroxidase; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase; D010424:Pentobarbital; D019331:NG-Nitroarginine Methyl Ester