Pre-treatment with the Na+/H+ exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia.
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 microM 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.
Rodríguez-Sinovas
Antonio
A
Laboratorio de Investigación Cardiovascular, Servicio de Cardiología, Hospitals Vall d'Hebron, Barcelona, Spain.
García-Dorado
David
D
Padilla
Ferran
F
Inserte
Javier
J
Barrabés
José Antonio
JA
Ruiz-Meana
Marisol
M
Agulló
Luis
L
Soler-Soler
Jordi
J
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D006146:Guanidines / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase