[en] Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely contributed to the discovery and to the validation of original treatments. The purpose of the present work was to develop and validate an original model of acute myocardial infarction provoked in pig by thrombosis of the left anterior descending (LAD) coronary artery induced by topical application of ferric chloride solution. Methods and results: Myocardial infarction, resulting from an occlusive and adherent mixed thrombus formed in the LAD coronary artery, was examined at macroscopic level using dual staining technique (Evans blue dye; triphenyltetrazolium chloride) and at microscopic level using conventional histological analyses and immunohistochemical detection of desmin. Biochemical markers (troponin T and ATP), platelet reactivity and standard hemodynamic parameters (such as stroke volume, ejection fraction, stroke work and cardiac output) have also been evaluated. From these analyses, it was demonstrated that each pig developed a transmural area of irreversible damage mainly located in the anteroseptal region of the left ventricle. The more progressive development of coronary artery occlusion, as compared to an abrupt Ligation, was accompanied by a correspondingly progressive impairment in hemodynamics. Conclusion: We conclude that this original porcine model of myocardial infarction is quite close to clinical pathophysiological conditions, such as thrombus formation occurring after atherosclerotic plaque rupture. This certainly constitutes a further argument in favour of this model to assess pharmaceutical or mechanical support of an acutely ischemic heart. (c) 2005 Elsevier Ltd. All rights reserved.
Disciplines :
Cardiovascular & respiratory systems Hematology
Author, co-author :
Dogné, Jean-Michel ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Rolin, Stéphanie
Petein, Michel
Tchana-Sato, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Ghuysen, Alexandre ; Université de Liège - ULiège > Département des sciences de la santé publique > Réanimation - Urgence extrahospitalière
Lambermont, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Magis, David ; Université de Liège - ULiège > Département de mathématique > Département de mathématique
Segers, Patrick
Pirotte, Bernard ; Université de Liège - ULiège > Chimie pharmaceutique
Masereel, Bernard
Drion, Pierre ; Université de Liège - ULiège > Centre animalier universitaire - Animalerie centrale
D'Orio, Vincenzo ; Université de Liège - ULiège > Département des sciences cliniques > Médecine d'urgence - bioch. et phys. hum. normales et path.
Kolh, Philippe ; Université de Liège - ULiège > Sciences biomédicales et précliniques > Biochimie et physiologie générale, humaine, normale et pathologique
M.A. DeWood, J. Spores, R. Notske, L.T. Mouser, R. Burroughs, and M.S. Golden Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction N Engl J Med 303 1980 897 902
M.J. Davies, and A. Thomas Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death N Engl J Med 310 1984 1137 1140
G.H. Tofler, D. Brezinski, A.I. Schafer, C.A. Czeisler, J.D. Rutherford, and S.N. Willich Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death N Engl J Med 316 1987 1514 1518
R.J. Leadley Jr., L. Chi, S.S. Rebello, and A. Gagnon Contribution of in vivo models of thrombosis to the discovery and development of novel antithrombotic agents J Pharmacol Toxicol Methods 43 2000 101 116
K.D. Kurz, B.W. Main, and G.E. Sandusky Rat model of arterial thrombosis induced by ferric chloride Thromb Res 60 1990 269 280
T. Tanaka, R. Sato, and T. Kurimoto Z-335, a new thromboxane A(2) receptor antagonist, prevents arterial thrombosis induced by ferric chloride in rats Eur J Pharmacol 401 2000 413 418
J.M. Dogne, J. Hanson, X. de Leval, P. Kolh, V. Tchana-Sato, and L. de Leval Pharmacological characterization of N-tert-butyl-N′-[2-(4′- methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time J Pharmacol Exp Ther 309 2004 498 505
G.V. Born, and M.J. Cross The aggregation of blood platelets J Physiol 168 1963 178 195
Y. Toki, N. Hieda, K. Okumura, H. Hashimoto, T. Ito, and K. Ogawa Myocardial salvage by a novel thromboxane A2 synthetase inhibitor in a canine coronary occlusion-reperfusion model Arzneimittelforschung 38 1988 224 227
K. Higo, A. Karasawa, and K. Kubo Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium J Pharmacobio-dyn 15 1992 33 37
S. Rolin, M. Petein, V. Tchana-Sato, J.M. Dogne, P. Benoit, and B. Lambermont BM-573, a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, prevents pig myocardial infarction induced by coronary thrombosis J Pharmacol Exp Ther 306 2003 59 65
M.C. Fishbein, J. Y-Rit, U. Lando, K. Kanmatsuse, J.C. Mercier, and W. Ganz The relationship of vascular injury and myocardial hemorrhage to necrosis after reperfusion Circulation 62 1980 1274 1279
B. Lauer, C. Niederau, U. Kuhl, M. Schannwell, M. Pauschinger, and B.E. Strauer Cardiac troponin T in patients with clinically suspected myocarditis J Am Coll Cardiol 30 1997 1354 1359
S.O. Vargas, B.A. Sampson, and F.J. Schoen Pathologic detection of early myocardial infarction: a critical review of the evolution and usefulness of modern techniques Mod Path 12 1999 635 645
L.H. Opie New concepts regarding events that lead to myocardial infarction Cardiovasc Drugs Ther 9 Suppl 3 1995 479 487
J.P. Chapelle Cardiac troponin I and troponin T: recent players in the field of myocardial markers Clin Chem Lab Med 37 1999 11 20
C. Chen, Q. Li, A.L. Darrow, Y. Wang, C.K. Derian, and J. Yang Mer receptor tyrosine kinase signaling participates in platelet function Arterioscler Thromb Vasc Biol 24 2004 1118 1123
S. Pan, L.S. Kleppe, T.A. Witt, C.S. Mueske, and R.D. Simari The effect of vascular smooth muscle cell-targeted expression of tissue factor pathway inhibitor in a murine model of arterial thrombosis Thromb Haemost 92 2004 495 502
M. Pynn, K. Schafer, S. Konstantinides, and M. Halle Exercise training reduces neointimal growth and stabilizes vascular lesions developing after injury in apolipoprotein e-deficient mice Circulation 109 2004 386 392
K. Schafer, S. Konstantinides, C. Riedel, T. Thinnes, K. Muller, and C. Dellas Different mechanisms of increased luminal stenosis after arterial injury in mice deficient for urokinase- or tissue-type plasminogen activator Circulation 106 2002 1847 1852
E.J. Weiss, J.R. Hamilton, K.E. Lease, and S.R. Coughlin Protection against thrombosis in mice lacking PAR3 Blood 100 2002 3240 3244
B. Zeng, D. Bruce, J. Kril, V. Ploplis, B. Freedman, and D. Brieger Influence of plasminogen deficiency on the contribution of polymorphonuclear leucocytes to fibrin/ogenolysis: studies in plasminogen knock-out mice Thromb Haemost 88 2002 805 810
D. Wu, K. Vanhoorelbeke, N. Cauwenberghs, M. Meiring, H. Depraetere, and H.F. Kotze Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons Blood 99 2002 3623 3628
J.C. Sill, B. Bertha, I. Berger, C. Uhl, M. Nugent, and J. Folts Human platelet Ca2+ mobilization, glycoprotein IIb/IIIa activation, and experimental coronary thrombosis in vivo in dogs are all inhibited by the inotropic agent amrinone Circulation 96 1997 1647 1653
H.S. Demrow, P.R. Slane, and J.D. Folts Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries Circulation 91 1995 1182 1188
J.K. Hennan, J. Huang, T.D. Barrett, E.M. Driscoll, D.E. Willens, and A.M. Park Effects of selective cyclooxygenase-2 inhibition on vascular responses and thrombosis in canine coronary arteries Circulation 104 2001 820 825
K. Wang, X. Zhou, Z. Zhou, K. Tarakji, M. Carneiro, and M.S. Penn Blockade of the platelet P2Y12 receptor by AR-C69931MX sustains coronary artery recanalization and improves the myocardial tissue perfusion in a canine thrombosis model Arterioscler Thromb Vasc Biol 23 2003 357 362
P. Cullen, R. Baetta, S. Bellosta, F. Bernini, G. Chinetti, and A. Cignarella Rupture of the atherosclerotic plaque: does a good animal model exist? Arterioscler Thromb Vasc Biol 23 2003 535 542
