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.
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.
Authors: Robert Flaumenhaft; Eiichi Tanaka; Gwenda J Graham; Alec M De Grand; Rita G Laurence; Kozo Hoshino; Roger J Hajjar; John V Frangioni Journal: Circulation Date: 2006-12-18 Impact factor: 29.690
Authors: James L Daniel; Carol A Dangelmaier; Sripal Mada; Lorena Buitrago; Jianguo Jin; Wallace Y Langdon; Alexander Y Tsygankov; Satya P Kunapuli; Archana Sanjay Journal: J Biol Chem Date: 2010-04-16 Impact factor: 5.157