Heart, Lung and Circulation
Original Article| Volume 16, ISSUE 2, P85-92, April 2007

Early-phase Endotoxic Shock-induced Myocardial Injury Increases iNOS and Selectin Expression in Macaque Primate


      Our previous study has established a macaque model with early-phase endotoxic shock. The present study further investigated myocardial and blood vessel injury in Macaques by examining the subsequent expression of ACP, selectins, iNOS, and cTnI in response to LPS treatment.


      In an experiment with anaesthetised, instrumental macaques, eleven animals were randomised into: an En group (n = 6), receiving a dose of 2.8 mg kg−1 lipopolysaccharides (LPS) by i.v.; and a Co group (n = 5), injected with normal saline of 1 ml kg−1. Cytochemistry of acid phosphatase (ACPase) in heart was performed by electron microscope at 120 min following endotoxin injection. Three immunochemical stains, namely, L-selectin, P-selectin and iNOS protein in heart, were studied. In addition, cardiac troponin I (cTnI), L-selectin and P-selectin in plasma were detected.


      In the early phase of endotoxic shock, LPS caused myocardial lysosome damage. The data of immunochemical staining showed the thrombus formation in vessels and the increase of iNOS, L-Selectin and P-Selectin expression in heart, but LPS challenge did not change L-selectin, P-selectin and cTnI in plasma.


      The increase of iNOS, L-selectin and P-selectin protein expression following endotoxin administration may have caused vessel injury and myocardial damage in macaques.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Heart, Lung and Circulation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Zhang N.
        • Weber A.
        • Li B.
        • Lyons R.
        • Contag P.R.
        • Purchio A.F.
        • et al.
        An inducible nitric oxide synthase-luciferase reporter system for in vivo testing of anti-inflammatory compounds in transgenic mice.
        J Immunol. 2003; 170: 6307-6319
        • Lyons C.R.
        • Orloff G.J.
        • Cunningham J.M.
        Molecular cloning and functional expression of an inducible nitric oxide synthase from murine macrophage cell line.
        J Biol Chem. 1992; 267: 6370-6374
        • Bolli R.
        Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research.
        J Mol Cell Cardiol. 2001; 33: 1897-1918
        • Andre P.
        P-selectin in haemostasis.
        Br J Haematol. 2004; 126: 298-306
        • van Zante A.
        • Rosen S.D.
        Sulphated endothelial ligands for L-selectin in lymphocyte homing and inflammation.
        Biochem Soc Trans. 2003; 31: 313-317
        • Ji X.H.
        • Sun K.Y.
        • Feng Y.H.
        • Yin G.Q.
        Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques.
        World J Gastroenterol. 2004; 10: 3026-3033
        • Snow T.R.
        • Dickey D.T.
        • Tapp T.
        • Hinshaw L.B.
        • Taylor F.B.
        Early myocardial dysfunction induced with endotoxin in rhesus monkeys.
        Can J Cardiol. 1990; 6: 130-136
        • Yin G.Q.
        • Qiu H.B.
        • Du K.H.
        • Tang J.Q.
        • Lu C.P.
        • Fang Z.X.
        Endotoxic shock model with fluid resuscitation in macaca mullatta.
        Lab Anim. 2005; 39: 269-279
        • Yin G.Q.
        • Ji X.H.
        • Gu F.R.
        • Lu C.P.
        • Fang Z.X.
        • Zhao W.
        • et al.
        Effect of fluid resuscitation on ryanodine receptor in macaques with endotoxic shock.
        Resuscitation. 2006; 70: 145-152
        • Yin G.Q.
        • Du K.H.
        • Zhong B.
        • Wang W.
        • Lin H.J.
        Membranous structure and lysosomal changes of myocardium in rabbits infected with meningococcus trough blood stream.
        China J Pathophys. 1998; 14: 669-672
        • Bollaert P.E.
        • Robin-Lherbier B.
        • Mallie J.P.
        • Nace L.
        • Escanye J.M.
        • Larcan A.
        Effects of sodium bicarbonate on striated muscle metabolism and intracellular pH during endotoxic shock.
        Shock. 1994; 1: 196-200
        • Zhang Y.S.
        • Liu Q.S.
        • Yin G.Q.
        • Zhong B.
        Effect of 5% sodium bicarbonate perfusion at different dose on cardiac function in rabbits with infective shock by Meningcoccus.
        J Nanjing Railway Med College. 1999; 18: 148-151
        • Lewis P.R.
        • Knight D.P.
        Cytochemical staining methods for electron microscopy.
        Elsevier Science Publishers BV, Amsterdam, Holland1992 (p. 147–204)
        • Leighty E.G.
        • Stoner C.D.
        • Ressallat M.M.
        • Tasananti G.T.
        • Sirak H.D.
        Effects of acute asphyxia and deep hypothermia on the state of binding of lysosomal acid hydrolases in canine cardiac muscle.
        Circ Res. 1967; 21: 59-64
        • Okada T.
        • Zinchuk V.S.
        • Seguchi H.
        Lipopolysaccharide administration increases acid and alkaline phosphatase reactivity in the cardiac muscle.
        Microsc Res Tech. 2002; 58: 421-426
        • Balligand J.L.
        • Ungureanu-Longrois D.
        • Simmons W.W.
        • Pimental D.
        • Malinski T.A.
        • Kapturczak M.
        • et al.
        Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro.
        J Biol Chem. 1994; 269: 27580-27588
        • Schulz R.
        Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats.
        Am J Physiol Heart Circ Physiol. 2002; 283: H1108-H1115
        • Boczkowski J.
        • Lanone S.
        • Ungureanu-Longrois D.
        • Danialou G.
        • Fournier T.
        • Aubier M.
        Induction of diaphragmatic nitric oxide synthase after endotoxin administration in rats: role on diaphragmatic contractile dysfunction.
        J Clin Invest. 1996; 98: 1550-1559
        • Khadour F.H.
        • Panas D.
        • Ferdinandy P.
        • Schulze C.
        • Csont T.
        • Lalu M.M.
        • et al.
        Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats.
        Am J Physiol Heart Circ Physiol. 2002; 283: H1108-H1115
        • Mebazaa A.
        • De Keulenaer G.W.
        • Paqueron X.
        • Andries L.J.
        • Ratajczak P.
        • Lanone S.
        • et al.
        Activation of cardiac endothelium as a compensatory component in endotoxin-induced cardiomyopathy: role of endothelin, prostaglandins, and nitric oxide.
        Circulation. 2001; 104: 3137-3144
        • Buttery L.D.
        • Evans T.J.
        • Springall D.R.
        • Carpenter A.
        • Cohen J.
        • Polak J.M.
        Immunochemical localization of inducible nitric oxide synthase in endotoxin-treated rats.
        Lab Invest. 1994; 71: 755-764
        • Braun-Dullaeus R.C.
        • Dietrich S.
        • Schoaff M.J.
        • Sedding D.G.
        • Leithaeuser B.
        • Walker G.
        • et al.
        Protective effect of 3-deazaadenosine in a rat model of lipopolysaccharide-induced myocardial dysfunction.
        Shock. 2003; 19: 245-251
        • Ammann P.
        • Fehr T.
        • Minder E.I.
        • Gunter C.
        • Bertel O.
        Elevation of troponin I in sepsis and septic shock.
        Intensive Care Med. 2001; 27: 959-961
        • Briassoulis G.
        • Narlioglou M.
        • Zavras N.
        • Hatzis T.
        Myocardial injury in meningococcus-induced purpura fulminant in children.
        Intensive Care Med. 2001; 27: 1073-1082
        • Dagan O.
        • Prince T.
        • Ben-Abraham R.
        • Vidne B.
        • Mishaly D.
        • Katz Y.
        • et al.
        Plasma soluble L-selectin following cardiopulmonary bypass (CPB) in children: is it a marker of the postoperative course?.
        Med Sci Monit. 2002; 8: CR467-CR472
        • Rainer T.H.
        • Lam N.Y.
        • Chan T.Y.
        • Cocks R.A.
        Early role of neutrophil L-selectin in posttraumatic acute lung injury.
        Crit Care Med. 2000; 28: 2766-2772
        • Seidelin J.B.
        • Nielsen O.H.
        • Strom J.
        Soluble L-selectin levels predict survival in sepsis.
        Intensive Care Med. 2002; 28: 1613-1618
        • Yin G.Q.
        • Qiu H.B.
        • Du K.H.
        • Tang J.Q.
        • Lu C.P.
        • Fang Z.X.
        Endotoxic shock model with fluid resuscitation in macaca mullatta.
        Lab Anim. 2006; 40: 104-106