| 14703716 |
Souktani R, Ghaleh B, Tissier R, d'Anglemont de Tassigny A, Aouam K, Bedossa P, Charlemagne D, Samuel J, Henry P, Berdeaux A: Inhibitors of swelling-activated chloride channels increase infarct size and apoptosis in rabbit myocardium. Fundam Clin Pharmacol. 2003 Oct;17(5):555-61.
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 +/- 31%, 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. |
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