title: Verapamil reduces coronary endothelium damage and cardiomyocyte necrosis but not apoptosis after ischemia and reperfusion: ex-vivo study in rat hearts.
abstract: We tested the hypothesis of beneficial effects of the calcium-blocker verapamil in a model of ischemia-reperfusion, and investigated its effects against coronary microcirculation and cardiomyocyte apoptosis. Isolated working rat hearts were subjected to 15 min global ischemia and 22-180 min reperfusion in the presence or absence of verapamil (0.25 &mgr;M). We evaluated creatinephosphokinase (CK) in coronary effluent, heart weight changes, microvascular permeability (extravasation of fluoresceine-labeled albumin), ultrastructural alterations, and cardiomyocyte apoptosis (by 1.5% agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling technique). In this model, 0.25 &mgr;M verapamil significantly reduced myocardial damage, CK release and vascular hyperpermeability, concomitant with a reduction in endothelial and cardiomyocyte lesions; on the contrary, 0.25 &mgr;M verapamil was unable to reduce cardiomyocyte apoptosis. In conclusion, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant verapamil concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte necrotic cell death but it is unable to reduce apoptotic cell death in isolated working rat hearts.
authors.affiliation: Lab. Exp. Cardiology, University of Chieti, Italy.
authors.forename: P.
authors.initials: P
authors.lastname: Di Napoli
authors.forename: A. A.
authors.initials: AA
authors.lastname: Taccardi
authors.forename: A.
authors.initials: A
authors.lastname: Grilli
authors.forename: M.
authors.initials: M
authors.lastname: Felaco
authors.forename: L.
authors.initials: L
authors.lastname: Di Gioacchino
authors.forename: R.
authors.initials: R
authors.lastname: De Caterina
authors.forename: A.
authors.initials: A
authors.lastname: Barsotti