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Na + /H + exchange inhibition protects against ischemic injury by preserving mitochondrial redox state, and by reducing mitochondrial Ca 2+ overload and ROS production
Author(s) -
Spence Marisha,
Aldakkak Mohammed,
Heisner James S,
Stowe David F,
Rhodes Samhita S,
Varadarajan Srinivasan G,
Camara Amadou KS
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1221-c
Subject(s) - chemistry , redox , hepes , ischemia , perfusion , reactive oxygen species , nuclear chemistry , biochemistry , inorganic chemistry , medicine
Inhibition of Na + /H + exchange (NHE) during ischemia reduces cardiac injury due to reduced Na + /Ca + exchange coupled to inhibited NHE. We tested if NHE inhibitor eniporide (ENI, 10 μM) given before and after ischemia better preserves mitochondrial redox (m redox ) state, reduces mCa 2+ overload and ROS production, and improves cardiac function. Guinea pig hearts (n=32) were perfused with HEPES buffer at pH 7.4 (control) and pH 8, with or without ENI, to test the effects of changes in ion gradients on post ischemic function. After baseline (BL) perfusion at pH 7.4, hearts were perfused with or without ENI at one of the two pHs for 10 min before and 10 min after 35 min ischemia; hearts were then reperfused for 110 min at pH 7.4. NADH, mCa 2+ (nM), and ROS were assessed using fiberoptic fluorescence; developed LVP (mmHg) and coronary flow (CF) were also measured. Compared to BL, at 60 min reperfusion m redox state was higher after pH7.4+ENI than pH 7.4 alone and was lowest after pH 8 alone. mCa 2+ increased less after pH 7.4+ENI (355±70) and more after pH 8 (844±140, compared to pH 7.4 (536±27); ENI reversed the rise in mCa 2+ (493±73) by pH 8. ROS was highest after pH 8, lower after pH 8+ENI, and lowest after pH 7.4+ENI. CF and LVP were highest after pH 7.4+ENI, lower after pH 8+ENI, and lowest after pH 8 alone. This shows that ENI counteracts pH 8 effects and better protects mitochondrial and cardiac function against ischemia reperfusion injury.