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 language | English |
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Journal | European journal of heart failure |
Volume | 7 |
Issue number | 1 |
Pages (from-to) | 29-35 |
Number of pages | 7 |
ISSN | 1388-9842 |
DOIs | |
Publication status | Published - 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