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Mitochondrial respiratory capacity is not markedly reduced in end‐stage human heart failure (15.6)
Author(s) -
Holzem Katherine,
Vinnakota Kalyan,
Ravikumar Vinod,
Beard Dan,
Efimov Igor
Publication year - 2014
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.28.1_supplement.15.6
Subject(s) - heart failure , oxidative phosphorylation , respiratory system , respiration , medicine , mitochondrion , palmitoylcarnitine , substrate (aquarium) , endocrinology , chemistry , cardiology , biology , biochemistry , anatomy , ecology
Objectives. We aimed to assess mitochondrial (Mt) substrate respiratory capacities in human donor (D) versus failing (F) hearts. Background. Heart failure (HF) is the end‐stage of cardiovascular disease, in which the heart can no longer sustain systemic metabolic demands. During HF progression, the heart switches energy substrate utilization from preferential use of fatty acids (FA) towards greater glucose consumption. We hypothesized that impaired Mt FA respiratory capacity may contribute to this substrate utilization shift. Methods. We isolated intact Mt from left ventricular (LV) tissue collected from D (n=7) and end‐stage F (F, n=9) human hearts and measured Mt respiration. Briefly, hearts were recovered in the operating room and cardioplegically arrested. Mt were isolated via differential centrifugation, and respiration measurements were collected with an oxygraph cell using ADP (350 μM) and pyruvate + malate (PM, 10 mM/2 mM) or palmitoylcarnitine (PC, 25 μM) as substrates. Results. For both substrates, we calculated the apparent capacity for oxidative phosphorylation (State 3) and respiratory control ratios (State 3/4 and State 3/2). In contrast with our hypothesis, Mt capacities for oxidative phosphorylation were not significantly reduced for F compared with D hearts for PM (195.9 ± 19.1 vs 158.8 ± 9.0 nM O2/min/mg, p = 0.12) or PC (122 ± 23.0 vs 91.9 ± 14.4 nM O2/min/mg, p = 0.19). Respiratory control ratios were also not different between D and F heart groups for either substrate. To control for myocardial Mt content, we assessed citrate synthase (CS) specific activity in LV muscle homogenates from the same hearts used for respiration measurements, which were consistent between D and F myocardium (14.5 ± 2.4 vs 14.7 ± 1.8 U/g). Conclusions. Mt respiratory capacities are not markedly impaired in end stage human HF for either glycolytic or FA substrates. Thus, the substrate utilization switch in HF does not appear to be the result of impaired Mt FA oxidation. Grant Funding Source : Supported by NHLBI R01HL11439501A1