Altered hetero- and homeometric autoregulation in the terminally failing human heart

Klara Brixius, Hannes Reuter, Wilhelm Bloch, Robert H G Schwinger

Publication: Contribution to journalJournal articlesResearch

Abstract

OBJECTIVE AND METHODS: To further investigate length-dependent force generation in human heart, nonfailing (donor hearts, NF) and terminally failing (heart transplants, dilated cardiomyopathy, DCM) left ventricular myocardium was studied under various preload (4-40 mN/mm2) or length conditions. In addition, morphological studies (van Giesson Trichrome staining, electron microscopy) were performed.

RESULTS: In NF, a biphasic increase in force of contraction (FOC) was observed after elevating the preload (4-40 mN/mm2): there was an immediate fast increase (FOCf,), followed by a slow increase over several minutes (FOCs), which was paralleled by an increase in the systolic fura-2 transient. In DCM, FOCf, FOCs and the systolic fura-2 transient were blunted and diastolic tension was increased at increasing muscle length. Only in NF, a stretched induced increase in diastolic fura-2 ratio was observed. In DCM, no obvious interstitial fibrosis and no difference in basement membrane structure and attachment were observed.

CONCLUSIONS: Since FOCf has been attributed to the Frank-Starling mechanism, whereas FOCs represents a length-dependent increase in the intracellular Ca2+-transient, the impaired length-dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca2+-sensitivity as well as the intracellular Ca2+-homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end-stage heart failure.

Original languageEnglish
JournalEuropean journal of heart failure
Volume7
Issue number1
Pages (from-to)29-35
Number of pages7
ISSN1388-9842
DOIs
Publication statusPublished - 01.01.2005

Research areas and keywords

  • Adult
  • Calcium Signaling
  • Cardiomyopathy, Dilated
  • Case-Control Studies
  • Female
  • Heart
  • Heart Ventricles
  • Homeostasis
  • Humans
  • Isometric Contraction
  • Male
  • Middle Aged
  • Myocardial Contraction
  • Myocardium
  • Tissue Culture Techniques
  • Weight-Bearing

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