Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion.

摘要: BACKGROUND Myocardial reperfusion is associated with calcium overload and cell contracture, mechanisms that may precipitate death. In this study, we tested the hypothesis in vivo inhibition of contracture could lead to preservation an open-chest large animal model. METHODS AND RESULTS Regional myocardium function was measured during a selective intracoronary infusion 2,3-butanedione monoxime (BDM), specific inhibitor actin-myosin coupling, control state (10 pigs) protocol 51-minute coronary occlusion followed by (40 pigs). The effects on artery blood flow basal were also studied (seven Intramyocardial distribution infusate occlusion, myocardial water content after 30 minutes area at risk, infarct size, type histological necrosis, geometry 24 hours assessed. Methods used included electromagnetic flowmeter, radiolabeled microspheres, subendocardial sonomicrometers, fluorescein, triphenyl tetrazolium chloride Masson's trichrome staining, computer quantification edges. absence ischemia, BDM inhibited regional shortening dose-dependent manner up full systolic bulging while producing marked increase flow. During early reperfusion, reduced end-diastolic length 76% more than (p less 0.05) increased 420% compared no change animals. ratio size/area risk 31% 0.05), striking modifications histology geometry; specifically, extent contraction band necrosis 63% from 105.5 +/- 18.2 39.2 13.6 mm2 0.02), patches (6.5 2.1 versus 1.6 0.4, p higher contour (7.7 1.2 5.03 0.2, fractal (12.1 1.3 7.8 indexes found. CONCLUSIONS Selective doses inhibiting wall motion decreased size reperfusion. function, reduction histology, peculiar configuration these infarcts all suggest can interfere cell-to-cell progression supporting role for reperfusion-induced