BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.
BACKGROUND:Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS:Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.
Authors: Jesper van der Pals; Michael I Götberg; Matthias Götberg; Lillemor Mattsson Hultén; Mia Magnusson; Sverker Jern; David Erlinge Journal: J Thromb Thrombolysis Date: 2011-07 Impact factor: 2.300
Authors: Jesper van der Pals; Matthias Götberg; Göran K Olivecrona; Helen Brogren; Sverker Jern; David Erlinge Journal: J Thromb Thrombolysis Date: 2010-04 Impact factor: 2.300
Authors: Gregory D Lewis; Ru Wei; Emerson Liu; Elaine Yang; Xu Shi; Maryann Martinovic; Laurie Farrell; Aarti Asnani; Marcoli Cyrille; Arvind Ramanathan; Oded Shaham; Gabriel Berriz; Patricia A Lowry; Igor F Palacios; Murat Taşan; Frederick P Roth; Jiangyong Min; Christian Baumgartner; Hasmik Keshishian; Terri Addona; Vamsi K Mootha; Anthony Rosenzweig; Steven A Carr; Michael A Fifer; Marc S Sabatine; Robert E Gerszten Journal: J Clin Invest Date: 2008-10 Impact factor: 14.808