Pre-treatment with the Na+/H+ exchange inhibitor cariporide delays cell-to-cell electrical uncoupling during myocardial ischemia.

Abstract

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.

• Authors: Antonio Rodríguez-Sinovas, David García-Dorado, Ferran Padilla, Javier Inserte, José Antonio Barrabés, Marisol Ruiz-Meana, Luis Agulló, Jordi Soler-Soler
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 58 Issue 1 Pg. 109-17 (Apr 01 2003) ISSN: 0008-6363 [Print] England
• PMID: 12667951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanidines
• Sodium-Hydrogen Exchangers
• Sulfones
• cariporide
• Adenosine Triphosphate
• L-Lactate Dehydrogenase

Topics

• Action Potentials (drug effects)
• Adenosine Triphosphate (metabolism)
• Animals
• Dose-Response Relationship, Drug
• Electric Impedance
• Guanidines (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (metabolism, prevention & control)
• Myocytes, Cardiac (drug effects)
• Perfusion
• Rats
• Rats, Sprague-Dawley
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Sulfones (pharmacology)
• Swine