Cardiomyocyte stiffness in diastolic heart failure

Attila Borbély, Jolanda Van Der Velden, Zoltán Papp, Jean G.F. Bronzwaer, Istvan Edes, Ger J.M. Stienen, Walter J. Paulus

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356 Citations (Scopus)

Abstract

Background - Heart failure with preserved left ventricular (LV) ejection fraction (EF) is increasingly recognized and usually referred to as diastolic heart failure (DHF). Its pathogenetic mechanism remains unclear, partly because of a lack of myocardial biopsy material. Endomyocardial biopsy samples obtained from DHF patients were therefore analyzed for collagen volume fraction (CVF) and sarcomeric protein composition and compared with control samples. Single cardiomyocytes were isolated from these biopsy samples to assess cellular contractile performance. Methods and Results - DHF patients (n=12) had an LVEF of 71 ± 11%, an LV end-diastolic pressure (LVEDP) of 28±4 mm Hg, and no significant coronary artery stenoses. DHF patients had higher CVFs (7.5±4.0%, P<0.05) than did controls (n=8, 3.8±2.0%), and no conspicuous changes in sarcomeric protein composition were detected, Cardiomyocytes, mechanically isolated and treated with Triton X-100 to remove all membranes, were stretched to a sarcomere length of 2.2 μm and activated with solutions containing varying [Ca2+]. Compared with cardiomyocytes of controls, cardiomyocytes of DHF patients developed a similar total isometric force at maximal [Ca2+], but their resting tension (Fpassive) in the absence of Ca2+ was almost twice as high (6.6±3.0 versus 3.5±1.7 kN/m2, P<0.001). F passive and CVF combined yielded stronger correlations with LVEDP than did either alone. Administration of protein kinase A (PKA) to DHF cardiomyocytes lowered Fpassive to control values. Conclusions - DHF patients had stiffer cardiomyocytes, as evident from a higher F passive, at the same sarcomere length. Together with CVF, F passive determined in vivo diastolic LV dysfunction. Correction of this high Fpassive by PKA suggests that reduced phosphorylation of sarcomeric proteins is involved in DHF.

Original languageEnglish
Pages (from-to)774-781
Number of pages8
JournalCirculation
Volume111
Issue number6
DOIs
Publication statusPublished - Feb 15 2005

Keywords

  • Collagen
  • Contractility
  • Diastole
  • Heart failure
  • Myocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Borbély, A., Van Der Velden, J., Papp, Z., Bronzwaer, J. G. F., Edes, I., Stienen, G. J. M., & Paulus, W. J. (2005). Cardiomyocyte stiffness in diastolic heart failure. Circulation, 111(6), 774-781. https://doi.org/10.1161/01.CIR.0000155257.33485.6D