Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations

Markus Meyer, Boris Keweloh, Konrad Güth, Jeffrey W. Holmes, Burkert Pieske, Stephan E. Lehnart, Hanjörg Just, Gerd Hasenfuss

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42 Scopus citations

Abstract

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n = 7), developed force decreased from 16.5 ± 4.3 to 7.9 ± 2.9 mN/mm2 (P < 0.01), diastolic force increased from 15.9 ± 3.2 to 22.0 ± 3.0 mN/mm2 (P < 0.01), and total MVO2 increased from 2.6 ± 0.6 to 4.7 ± 0.9 ml/min/100g (P < 0.025). Resting MVO2 and resting force were 1.8 ± 0.4 ml/min/100 g and 15.9 ± 3.0 mN/mm2, respectively. After addition of 30 mM 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P < 0.05) and 15% (P < 0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r = 0.96 ± 0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force.

Original languageEnglish (US)
Pages (from-to)1459-1470
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number8
DOIs
StatePublished - Aug 1998
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by grants from the Deutsche Forschungsgemeinschaft (HA 1233/3-2) and from the Bundesministerium für Wissenschaft, Bi-ldung, Forschung und Technologie (BMFT 0311006). G. Hasenfuss is an Established Investigator of the Deutsche Forschungsgemeinschaft (DFG, Heisenberg-Stipendium HA 1233/4-1). J. Holmes was supported by the Alexander-von-Humboldt Stiftung.

Keywords

  • Cross-bridge cycling
  • Diastolic function
  • Force-frequency relation
  • Heart failure
  • Myocardial oxygen consumption

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