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Acidotic perfusion protects against ischemic injury by improving mitochondrial redox balance
Author(s) -
Camara Amadou K.S.,
Aldakkak Mohammed,
Heisner James S,
Rhodes Samhita S,
Heinen Andre,
Varadarajan Srinivasan G,
Riess Matthias L,
Stowe David F
Publication year - 2006
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.20.4.a742-b
Subject(s) - acidosis , chemistry , intracellular ph , ischemia , redox , hepes , perfusion , extracellular , biochemistry , medicine , inorganic chemistry
Extracellular acidosis during ischemia reperfusion (IR) reduces cardiac injury due to slowed Na/H and Na/Ca exchange. We tested if acidosis also protects mitochondria. We compared effects of changes in pH o on altering redox state during IR. Guinea pig hearts were perfused with HEPES buffer to reduce changes in [Ca 2+ ] o . Groups: pH 7.4, pH 7.0+16 mM K + (cardioplegia, CP) and pH 8.0. After baseline (BL) hearts were perfused at one pH for 10 min before and 10 min after 35 min 37°C ischemia and then at pH 7.4 for 110 min. LVP and coronary flow (CF) were recorded and NADH, FAD and superoxide (O 2 ·− ) assessed by fluorescence (F) at the LV free wall. All data vs. BL. At 35 min ischemia O 2 ·− F increased by 32±11, 79±3 and 84±5% in pH 7+CP, pH 7.4 and pH 8; NADH F decreased by 5±1, and 8±1% in pH 7.4 and pH 8, but increased in pH 7+CP by 11±2%; FAD F decreased in pH 7+CP and increased in pH 7.4 and pH 8. At 60 min reperfusion, LVP and CF (100% BL) were 30±8% and 51±5% (pH 7.4), 60±8% and 76±5% (pH 7+CP), and 18±4% and 20±6% (pH 8); NADH, FAD and O 2 ·− F were less altered after pH 7+CP. This shows that low pH with CP, not only protects hearts, but also improves mitochondrial function during IR. Mitochondrial Ca 2+ entry during IR is less at low pH o and higher at high pH o . Low pH o improved the redox state (less altered NADH and FAD), and reduced the rise in O 2 ·− during ischemia, so the better return of contractility on reperfusion may be in part due to preserved mitochondrial function.