RGD Reference Report - Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats. - Rat Genome Database

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Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats.

Authors: Schoots, IG  Levi, M  Van Vliet, AK  Maas, AM  Roossink, EH  Van Gulik, TM 
Citation: Schoots IG, etal., Crit Care Med. 2004 Jun;32(6):1375-83.
RGD ID: 11250409
Pubmed: PMID:15187522   (View Abstract at PubMed)

OBJECTIVE: To examine whether administration of activated protein C or antithrombin reduces local splanchnic derangement of coagulation and inflammation and attenuates intestinal dysfunction and injury following intestinal ischemia/reperfusion. DESIGN: Randomized prospective animal study. SETTING: University research institute. SUBJECTS: Adult male Wistar rats, weighing 300-325 g (n = 72). INTERVENTIONS: Rats were subjected to superior mesenteric artery occlusion consisting of 20 or 40 mins of ischemia and 3 hrs of reperfusion. A randomized intravenous administration of vehicle (0.9% NaCl), heparin, antithrombin, or activated protein C was performed during ischemia, 15 mins before reperfusion. Coagulation and fibrinolysis variables obtained from portal blood were correlated with mucosal fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance), and intestinal injury (histologic evaluation by Park/Chiu score). MEASUREMENTS AND MAIN RESULTS: Activated protein C- or antithrombin-treated animals demonstrated less ischemia/reperfusion-induced intestinal dysfunction and histologic changes compared with control animals, whereas intravenous administration of heparin only showed less histologic derangement. Activated protein C- or antithrombin-treated animals showed less thrombin generation, fibrin degradation products, and fibrin deposition compared with control animals, as confirmed by histologic examination, whereas heparin administration showed only a limited reduction of portal fibrin degradation product concentrations. Furthermore, activated protein C or antithrombin administration markedly inhibited the inflammatory response, as reflected by reduced interleukin-6 plasma concentrations to baseline values, whereas heparin had no effect. CONCLUSIONS: Administration of activated protein C or antithrombin inhibited local and systemic derangement of coagulation and inflammation following intestinal ischemia/reperfusion, diminished mucosal fibrin deposition, and attenuated ischemia/reperfusion-induced intestinal injury. These observations suggest that activated protein C or antithrombin reduces ischemia/reperfusion-induced intestinal injury, both through their anticoagulant and anti-inflammatory effects.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Intestinal Reperfusion Injury treatmentIDA 11250409 RGD 
Intestinal Reperfusion Injury treatmentISOPROC (Homo sapiens)11250409; 11250409 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Proc  (protein C, inactivator of coagulation factors Va and VIIIa)

Genes (Mus musculus)
Proc  (protein C)

Genes (Homo sapiens)
PROC  (protein C, inactivator of coagulation factors Va and VIIIa)


Additional Information