Premium
Reversible, brief blockade of mitochondrial respiration at the onset of reperfusion decreases myocardial injury in aging hearts
Author(s) -
Chen Qun,
Ross Thomas,
Hu Ying,
Lesnefsky Edward J
Publication year - 2011
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.25.1_supplement.1033.4
Subject(s) - blockade , oxidative phosphorylation , mitochondrion , ischemia , cardiology , inner mitochondrial membrane , membrane potential , chemistry , medicine , pharmacology , biochemistry , receptor
Signaling‐based modulation of mitochondria (MITO) during reperfusion (REP) by post‐conditioning unfortunately does not protect the aged heart. We reasoned that direct, transient pharmacologic blockade of oxidative phosphorylation (OXPHOS) would bypass upstream defects and protect. Amobarbital (AMO, 2.5 mM), a rapid and reversible inhibitor, was given for the first 3 min. of REP. Langendorff‐perfused Fischer 344 aged (24 mo.) rat hearts underwent 25 min. global ischemia (ISC) and 30 min REP with or without AMO. AMO decreased LDH release during REP, indicating less cardiac cell death. AMO preserved mitochondrial inner membrane potential (TMRM fluorescence isolated MITO). Since damage to OXPHOS occurs during ISC, AMO could not restore maximal rates (glutamate as substrate). ISC decreased left ventricular developed pressure (LVDP, mmHg) compared to pre‐ISC and AMO did not improve function (persistent stunning). Thus, the direct, brief blockade of respiration immediately at REP decreases injury in aged hearts by protecting the integrity of the inner MITO membrane.Table Untreated REP (n=10) AMO+REP (n=9)Hemodynamic data LVDP‐Pre‐ISC 127 ±3 125 ± 2 LVDP‐REP 55 ± 10 65 ± 8 LDH 719 ± 37 543 ± 39 † Oxidative phosphorylation SSM 94 ± 10 113 ± 11 IFM 123 ± 11 151 ± 15 Mitochondrial inner membrane potential SSM 0.101 ± 0.009 0.125 ± 0.008 † IFM 0.121 ± 0.011 0.153 ± 0.009 †Mean ± SE, † P<0.05 AMO vs. ISC‐REP. SSM‐subsarcolemmal MITO, IFM‐interfibrillar MITO.Supported by 2PO1AG15885 NIA.