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Activated Protein C and Normal Saline Infusion Might Prevent Deleterious Effects of Remote Acute Lung Injury Caused by Intestinal Ischemia-Reperfusion: An Experimental Study in the Rat Model

Published:December 31, 2009DOI:https://doi.org/10.1016/j.jss.2009.12.002

      Background

      Intestinal ischemia-reperfusion is a common medical event associated with both clinical and experimental distant organ injury. In particular, the lung tissue appears to be susceptible to injury resulting from systemic inflammatory mediator activation. Drotrecogin α (activated) or recombinant human activated protein C has antithrombotic, anti-inflammatory, and profibrinolytic properties. We hypothesized that APC infusion would decrease lung inflammation and ameliorate lung injury resulting from intestinal ischemia-reperfusion (IIR). A rat model of intestinal ischemia-reperfusion was used to test this hypothesis, and several parameters of lung injury were measured in lung samples.

      Material and Methods

      Forty Wistar albino rats were divided into four groups: a sham-operated group (Sham), an ischemic control group (IIR), an APC-infusion group (IIR'APC), and a normal saline-infusion group (IIR'NS) (n = 10, each). A marker for lipid peroxidation, malondialdehyde (MDA), free radical scavenger glutathione peroxidase (GSH-Px), an index of polymorphonuclear neutrophils, myeloperoxidase (MPO) activity, and lung polymorphonuclear leukocytes (PMNL) were investigated in the lung tissue samples.

      Results

      MDA and MPO levels, and lung PMNL sequestration were decreased, but GSH-Px levels were increased in APC treated group versus IIR group. MDA levels were decreased and GSH-Px levels were increased in NS treated group versus IIR group. MPO levels and lung PMNL counts were similar across the IIR and IIR'NS groups.

      Conclusions

      This study documents that APC attenuates acute lung injury in intestinal ischemia-reperfusion. NS infusion had also some favorable effects regarding MDA and MPO.

      Key Words

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      References

        • Kostopanagiotou G.
        • Avgerinos E.
        • Costopanagiotou C.
        • et al.
        Acute lung injury in a rat model of intestinal ischemia-reperfusion: The potential time depended role of phospholipases A(2).
        J Surg Res. 2008; 147: 108
        • Murphy J.
        • Turnage R.H.
        Experimental models and endpoints for studies of intestinal ischemia-reperfusion injury.
        in: Souba W.W. Wilmore D.W. Surgical research. Academic Pres, San Diego, CA2001: 583
        • Grotz M.R.
        • Deitch E.A.
        • Ding J.
        • et al.
        Intestinal cytokine response after gut ischemia: Role of gut barrier failure.
        Ann Surg. 1999; 229: 478
        • Oldham K.T.
        • Guice K.S.
        • Magee T.C.
        The systemic consequences of intestinal ischemia/reperfusion injury.
        J Vasc Surg. 1993; 18: 136
        • Schmeling D.J.
        • Caty M.G.
        • Oldham K.T.
        • et al.
        Evidence for neutrophil-related acute lung injury after intestinal ischemia-reperfusion.
        Surgery. 1989; 106: 195
        • Simpson R.
        • Alon R.
        • Kobzik L.
        • et al.
        Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion.
        Ann Surg. 1993; 218: 444
        • Bernard G.R.
        • Vincent J.L.
        • Laterre P.F.
        • et al.
        Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis.
        N Engl J Med. 2001; 344: 699
        • Stechmiller J.K.
        • Treloar D.
        • Allen N.
        Gut dysfunction in critically ill patients: A review of the literature.
        Am J Crit Care. 1997; 6: 204
        • Gollin G.
        • Zieg P.M.
        • Cohn S.M.
        • et al.
        Intestinal mucosal injury in critically ill surgical patients: Preliminary observations.
        Am Surg. 1999; 65: 19
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • et al.
        Protein measurement with the Folin phenol reagent.
        J Biol Chem. 1951; 193: 265
        • Draper H.H.
        • Hadley M.
        Malondialdehyde determination as index of lipid peroxidation.
        Methods Enzymol. 1990; 186: 421
        • Grisham M.B.
        • Hernandez L.A.
        • Granger D.N.
        Xanthine oxidase and neutrophil infiltration in intestinal ischemia.
        Am J Physiol. 1986; 251: 567
        • Tetik C.
        • Ozden A.
        • Calli N.
        • et al.
        Cytoprotective effect of trimetazidine on 60 minutes of intestinal ischemia-reperfusion injury in rats.
        Transpl Int. 1999; 12: 108
        • Paglia D.E.
        • Valentine W.N.
        Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.
        J Lab Clin Med. 1967; 70: 158
        • Caty M.G.
        • Guice K.S.
        • Oldham K.T.
        • et al.
        Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury.
        Ann Surg. 1990; 212 (PubMed PMID: 2175168; PubMed Central PMCID: PMC1358254): 694
        • Gerkin T.M.
        • Oldham K.T.
        • Guice K.S.
        • et al.
        Intestinal ischemia-reperfusion injury causes pulmonary endothelial cell ATP depletion.
        Ann Surg. 1993; 217: 48
        • Köksoy C.
        • Kuzu M.A.
        • Ergün H.
        • et al.
        Intestinal ischemia and reperfusion impairs vasomotor functions of pulmonary vascular bed.
        Ann Surg. 2000; 231: 105
        • Yao Y.M.
        • Bahrami S.
        • Redl H.
        • et al.
        Monoclonal antibody to tumor necrosis factor-α attenuates hemodynamic dysfunction secondary to intestinal ischemia/reperfusion in rats.
        Crit Care Med. 1996; 24: 1547
        • Sorkine P.
        • Szold O.
        • Halpern P.
        • et al.
        Gut decontamination reduces bowel ischemia-induced lung injury in rats.
        Chest. 1997; 112: 491
        • Grotz M.R.
        • Deitch E.A.
        • Ding J.
        • et al.
        Intestinal cytokine response after gut ischemia: Role of gut barrier failure.
        Ann Surg. 1999; 229: 478
        • Lane J.S.
        • Todd K.E.
        • Lewis M.P.
        • et al.
        Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.
        Surgery. 1997; 122: 288
        • Simms H.H.
        Models of adult respiratory distress syndrome-aspiration.
        in: Souba W.W. Wilmore D.W. Surgical research. Academic Pres, San Diego, CA2001: 393
        • Savas M.C.
        • Ozguner M.
        • Ozguner I.F.
        • et al.
        Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury.
        J Pediatr Surg. 2003; 38: 1465
        • Teke Z.
        • Sacar M.
        • Yenisey C.
        • et al.
        Activated protein C attenuates intestinal reperfusion-induced acute lung injury: An experimental study in a rat model.
        Am J Surg. 2008; 195: 861
        • Murphy J.
        • Turnage R.H.
        Experimental models and endpoints for studies of intestinal ischemia-reperfusion injury.
        in: Souba W.W. Wilmore D.W. Surgical research. Academic Pres, San Diego, CA2001: 591
        • Turnage R.H.
        • Guice K.S.
        • Oldham K.T.
        The effects of hypovolemia on multiple organ injury following intestinal reperfusion.
        Shock. 1994; 1: 408