Chronic Myocardial Ischemia Leads to Loss of Maximal Oxygen Consumption and Complex I Dysfunction

David A. Schipper, Ryan Palsma, Katherine M. Marsh, Connor O'Hare, Destiny S. Dicken, Scott Lick, Toshinobu Kazui, Kitsie Johnson, Ryszard T. Smolenski, Dirk J. Duncker, Zain Khalpey

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background Cardiomyocytes rely heavily on mitochondrial energy production through oxidative phosphorylation. Chronic myocardial ischemia may cause mitochondrial dysfunction and affect ATP formation. Metabolic changes due to ischemia alters cardiac bioenergetics and hence myocardial function and overall bioenergetic state. Here, we evaluate differences in functional status of respiratory complexes in mitochondrial isolates extracted from left atrial appendage tissue (LAA) from patients undergoing cardiac surgery, with and without chronic ischemia. Methods Mitochondrial isolates were extracted from LAA in ischemic coronary artery bypass grafting patients (n = 8) and non-ischemic control patients (n = 6) undergoing other cardiac surgery (valve repair/replacement). Coupling and electron transport chain assays were performed using Seahorse XFe 96 (Agilent Technologies, Santa Clara, CA) analyzer. Oxygen consumption rates were measured to calculate respiration states. Results Respiratory control rate (RCR) in ischemic patients was significantly lower than control patients (6.17 ± 0.27 vs 7.11 ± 0.31, respectively; p < 0.05). This is the result of minimal, non-significant state 3ADP and state 4O changes in chronic ischemia. Complex I respiration is diminished in ischemic tissue (99.1 ± 14.9 vs 257.8 ± 65.2 in control; p < 0.01). Maximal complex I/II respiration ratio was significantly lower in ischemic patients (58.9% ± 5.5% vs 90.9% ± 8.8%; p < 0.05), a difference that was also seen in complex I/IV ratios (p < 0.05). There was no significant difference in complex II/IV ratios between groups. Conclusions Ischemic patients have aberrant mitochondrial function, highlighted by a lowered RCR. All ratios involving complex I were affected, suggesting that the insufficient ATP formation is predominantly due to complex I dysfunction. Complex II and IV respiration may be impaired as well, but to a lesser extent.

Original languageEnglish (US)
Pages (from-to)1298-1304
Number of pages7
JournalAnnals of Thoracic Surgery
Issue number4
StatePublished - Oct 2017
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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