Recombinant Soluble P-Selectin Glycoprotein Ligand-Ig (rPSGL-Ig) Attenuates Infarct Size and Myeloperoxidase Activity in a Canine Model of Ischemia-Reperfusion

Summary

The role of P-selectin in the process of reperfusion injury was evaluated using a recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in a canine coronary artery balloon occlusion model. rPSGL-Ig (1 mg/kg) or saline was given as an intravenous bolus 15 min before balloon deflation. Balloon occlusion time was 90 min followed by either 120 min or 7 days reperfusion. Infarct size was significantly reduced in the treatment group when expressed either as percentage of the area at risk or as absolute infarct size. Histological analysis showed that extensive myocardial injury and neutrophil infiltration were reduced by rPSGL-Ig. Myeloperoxidase activity (MPO) was significantly reduced in the risk area in the rPSGL-Ig group. Left ventricular ejection fraction was significantly less impaired during the first 24 h after reperfusion in the rPSGL-Ig group, although there was no difference by 7-day follow-up. Thus, administration of rPSGL-Ig decreases myocardial injury and inflammatory response for at least 7 days after reperfusion of ischemic myocardium.

Keywords

P-selectin - rPSGL-Ig - inflammatory response - reperfusion injury

• References

• 1 Ellis SG, Henschke CI, Sander T, Wynne J, Braunwald K, Kloner RA. Time course of functional and biochemical recovery of myocardium salvaged by reperfusion. J Am Coll Cardiol 1983; 01: 1047-55.
• 2 Bush LR, Buja LM, Samowitz W, Rude RE, Wathen M, Tilton GD, Willerson JT. Recovery of left ventricular segmental function after long-term reperfusion following temporary coronary occlusion in conscious dogs. Circ Res 1983; 53: 248-63.
• 3 Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival: should the paradigm be expanded?. Circulation 1989; 53: 248-63.
• 4 Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword?. J Clin Invest 1985; 76: 1713-9.
• 5 Whalen DA, Hamilton DG, Ganote CE, Jennings RB. Effect of a transient period of ischemia on myocardial cells. I. Effects of cell volume regulation. Am J Pathol 1974; 74: 381-98.
• 6 Kloner RA, Ganote CE, Whalen DA, Jennings RB. Effect of a transient period of ischemia on myocardial cells. II. Fine structuring during the first few minutes of reflow. Am J Pathol 1974; 74: 399-422.
• 7 Forman MB, Virmani R, Puett DW. Mechanism and therapy of myocardial reperfusion injury. Circulation. 1990 81. (suppl IV): IV-69-IV-78.
• 8 Lucchesi B, Mullane K. Leukocytes and ischemic-induced myocardial injury. Annu Rev Pharmacol Toxicol 1986; 26: 201-24.
• 9 Tsao PS, Aoki N, DJ Lefer, Johnson III G, AM Lefer. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the rat. Circulation 1990; 82: 1402-12.
• 10 Opie I. Reperfusion injury and its pharmacologic modification. Circulation 1989; 80: 1049-62.
• 11 Kloner R, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion: resolved and unresolved issues. Circulation 1989; 80: 1115-27.
• 12 Engler R, Covell J. Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog. Circ Res 1987; 61: 20-8.
• 13 McEver RP. Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb Haemost 2001; 86: 746-56.
• 14 Romson J, Hook B, Kunel S, Abrams G, Schork M, Lucchesi B. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation 1983; 67: 1016-23.
• 15 Mullane K, Read N, Salmon J, Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs. J Pharmacol Exp Ther 1984; 228: 510-22.
• 16 Simpson P, Todd III R, Mickelson J, Fantone J, Gallagher K, Lee K, Tamura Y, Cronin M, Lucchesi B. Sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alters leukocyte function. Circulation 1990; 81: 226-37.
• 17 Silver M, Sutton J, Hook S, Lee P, Malycky J, Phillips ML, Ellis SG, Topol EJ, Nicolini F. Adjunctive selectin blockade successfully reduces infarct size beyond thrombolysis in the electrolytic canine coronary artery model. Circulation 1995; 92: 492-9.
• 18 Sako D, Chang XJ, Barone KM. et al. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 1993; 75: 1179-86.
• 19 Sako D, Comess KM, Barone KM. et al. A sulfated peptide segment at the amino terminus of PSGL-1 critical for P-selectin binding. Cell 1995; 83: 323-31.
• 20 Kumar R, Camphausen RT, Sullivan FX, Cumming DA. Core 2 13-1,6-Nacetylglucosaminyltransferase enzyme activity is critical for P-selectin glycoprotein ligand-1 binding to P-selectin. Blood 1996; 88: 3872-9.
• 21 Schierwagen C, Bylund-Fellenius AC, Lundberg C. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharm Methods 1990; 23: 179-86.
• 22 Qin JX, Jones M, Shiota T, Greenberg NL, Tsujino H, Firstenberg MS, Gupta PC, Zetts AD, Xu Y, Sun JP, Cardon LA, Odabashian JA, Flamm SD, White RD, Panza JA, Thomas JD. Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies. J Am Coll Cardiol 2000; 36: 900-7.
• 23 Qin JX, Shiota T, McCarthy PM, Firstenberg MS, Greenberg NL, Tsujino H, Bauer F, Travaglini A, Hoercher KJ, Buda T, Smedira NG, Thomas JD. Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy. Circulation. 2000 102. [suppl III]:III-101-III-106..
• 24 Ahmad M, Xie T, McCulloch M, Abre G, Runge M. Real-time three-dimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: comparison with two-dimensional dobutamine stress echocardiography. J Am Coll Cardiol 2001; 37: 1303-9.
• 25 Adams DH, Shaw S. Leukocyte-endothelial interactions and regulation of leukocyte migration. Lancet 1994; 343: 831-6.
• 26 McEver RP. Leukocyte-endothelial cell interaction. Curr Opin Cell Biol 1992; 04: 840-9.
• 27 Smith CW, Kishimoto TK, Abbass O, Hughes B, Rothlein R, McIntire LV, Butcher E, Anderson DC. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. J Clin Invest 1991; 87: 609-18.
• 28 Lawrence MB, Springer TA. Leukocytes roll on selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991; 65: 859-73.
• 29 Von Adrian UH, Chambers JD, McEvoy LM, Bargatze RF, Arfors K-E, Butcher EC. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and leukocyte 132 integrins in vivo. Proc Natl Acad Sci USA 1991; 88: 7538-42.
• 30 Weyrich AS, Ma XL, Lefer DJ, Albertine KH, Lefer AM. In vivo neutralization of P-selectin protects feline heart and endothelium in myocardium ischemia and reperfusion injury. J Clin Invest 1993; 91: 2620-9.
• 31 Flynn DM, Buda AJ, Jeffords PR, Lefer DJ. A sialyl Lewis-containing carbohydrate reduces infarct size: role of selectins in myocardial reperfusion injury. Am J Physiol 1996; 271: H2086-H2096.
• 32 Hayward R, Campbell B, Shin YK, Scalia R, Lefer AM. Recombinant soluble P-selectin glycoprotein ligand-1 protects against myocardial ischemic reperfusion injury in cats. Cardiovasc Res 1999; 41: 65-76.
• 33 Ikeda H, Ueyama T, Murohara T, Yasukawa H, Haramaki N, Eguchi H, Katoh A, Takajo Y, Onitsuka I, Ueno T, Tojo SJ, Imaizumi T. Adhesive interaction between P-selectin and sialyl Lewisx plays an important role in recurrent coronary arterial thrombosis in dogs. Arterioscler Thromb Vasc Biol 1999; 19: 1083-90.
• 34 Perez RG, Arai M, Richardson C, DiPaula A, Siu C, Matsumoto N, Hildreth JEK, Mariscalco MM, Smith CW, Becker LC. Factors modifying protective effect of anti-CD18 antibodies on myocardial reperfusion injury in dogs. Am J Physiol 1996; 270: H53-H64.
• 35 Arai M, Lefer DJ, So T, DiPaula A, Aversano T, Becker LC. An anti-CD18 antibody limits infarct size and preserve left ventricular function in dogs with ischemia and 48-hour reperfusion. J Am Coll Cardiol 1996; 27: 1278-85.
• 36 Ma XI, Lefer DJ, Lefer AM, Rothlein R. Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesive molecule-1 in myocardial ischemia and reperfusion. Circulation 1992; 86: 937-46.
• 37 Ma XL, Weyrich AS, Lefer DJ, Lefer AM. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res 1993; 72: 403-12.
• 38 Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991; 88: 4651-5.
• 39 Heller R, Bussolino F, Ghigo D, Garbarino G, Pescarmona G, Till U, Bosia A. Nitrovasodilators inhibit thrombin-induced platelet-activating factor synthesis in human endothelial cells. Biochem Pharmacol 1992; 44: 223-9.
• 40 Niu XF, Smith CW, Kubes P. Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils. Circ Res 1994; 74: 1133-40.
• 41 Gries A, Bode C, Peter K, Herr A, Bohrer H, Motsch J, Martin E. Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro and in vivo. Circulation 1998; 97: 1481-7.
• 42 Lefer AM, Campbell B, Scalia R, Lefer DJ. Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion. Role of selectins. Circulation 1998; 98: 1322-8.
• 43 Kumar A, Villani MP, Patel UK, Keith Jr JC, Schaub RG. Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model. Circulation 1999; 99: 1363-9.
• 44 Andre P, Hartwell D, Hrachovinova I, Saffaripour S, Wagner DD. Procoagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci USA 2000; 97 (25) 13835-40.