© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Pre-treatment with the Na+/H+ exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia
Laboratorio de Investigación Cardiovascular, Servicio de Cardiología, Hospitals Vall d’Hebron, Pg. Vall d’Hebron 119–129, 08035 Barcelona, Spain
* Corresponding author. Tel.: +34-93-489-4038; fax: +34-93-489-4032. dgdorado{at}hg.vhebron.es
Objective: Inhibition of Na+–H+ exchange (NHE) delays the onset of myocardial rigor contracture during ischemia. The aim of this study was to analyse the effects of NHE inhibition on cell-to-cell electrical uncoupling during myocardial ischemia/reperfusion. Methods: Twenty-six isolated rat hearts and 23 in situ porcine hearts were submitted to no-flow ischemia followed by reperfusion, with or without pre-treatment with cariporide (7 µM in rats and 3 mg/kg in pigs). Ischemic rigor and hypercontracture, conduction velocity and myocardial electrical impedance were monitored. Results: Pre-treatment with cariporide delayed ATP depletion (luminescence assay in rat myocardium) and onset of rigor contracture (tension recordings or ultrasonic crystals) during ischemia both in rat and pig hearts (P<0.05). In addition, cariporide delayed the onset of sharp changes in tissue resistivity and phase angle in impedance recordings (four-electrode probes) from 10±1 to 13±1 min (P<0.001) in rat hearts, and from 22±1 to 38±2 min (P<0.001) in pigs. Blockade of impulse propagation (transmembrane action potentials in rat hearts) was also markedly delayed by cariporide (from 14±1 to 20±1 min, P<0.001). Reperfusion-induced LDH release in rat hearts and infarct size in pigs were markedly reduced by pre-treatment with cariporide. Conclusions: Inhibition of NHE with cariporide slows the progression of ischemic injury during myocardial ischemia, and delays the onset of cell-to-cell electrical uncoupling.
KEYWORDS Conduction (block); Gap junctions; Ischemia; Na/H-exchanger; Reperfusion
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