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Inhibitors of swelling‐activated chloride channels increase infarct size and apoptosis in rabbit myocardium
Author(s) -
Souktani Rachid,
Ghaleh Bijan,
Tissier Renaud,
De Tassigny Alexandra d'Anglemont,
Aouam Karim,
Bedossa Pierre,
Charlemagne Danièle,
Samuel Janelyse,
Henry Patrick,
Berdeaux Alain
Publication year - 2003
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2003.00175.x
Subject(s) - apoptosis , ischemia , tunel assay , chloride channel , medicine , myocardial infarction , chemistry , cardiology , anesthesia , pharmacology , andrology , biochemistry
Apoptosis is a significant contributor to myocardial cell death during ischemia‐reperfusion and swelling‐activated chloride channels (I Cl,swell ) contribute to apoptosis. However, the relationship between I Cl,swell , ischemia‐reperfusion and apoptosis remains unknown. To further investigate this, New Zealand rabbits underwent a 20‐min coronary artery occlusion (CAO) followed by 72 h of coronary artery reperfusion (CAR). Two I Cl,swell blockers, 5‐nitro‐2‐[3‐phenylpropylamino]benzoic acid (NPPB) and indanyloxyacetic acid 94 (IAA‐94) (both 1 mg/kg), were administered prior to CAO and throughout the 72 h CAR. Infarct size (IS) was increased with NPPB and IAA‐94 compared with control (vehicle) rabbits (51 ± 2% and 48 ± 3% and vs. 35 ± 2%, respectively, P < 0.05). Similar results were found when NPPB was administered only during the reperfusion period. The percentage of TUNEL‐positive nuclei in the border zone of the infarct was increased with NPPB compared with control (37 ± 2% vs. 25 ± 3%, P < 0.05) as well as the number of cytoplasmic histone‐associated DNA fragments (0.45 ± 0.06 vs. 0.33 ± 0.04 absorbance units, P < 0.05). These findings support the concept that I Cl,swell channels play an important role in the determination of myocardial infarct size and apoptosis during ischemia‐reperfusion.