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Altered hetero‐ and homeometric autoregulation in the terminally failing human heart
Author(s) -
Brixius Klara,
Reuter Hannes,
Bloch Wilhelm,
Schwinger Robert H.G.
Publication year - 2005
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2004.03.018
Subject(s) - preload , cardiology , medicine , heart failure , frank–starling law of the heart , diastole , myofilament , hypertensive heart disease , homeostasis , dilated cardiomyopathy , myocyte , endocrinology , blood pressure , hemodynamics , stroke volume , ejection fraction
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/mm 2 ) 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/mm 2 ): there was an immediate fast increase (FOC f ,), followed by a slow increase over several minutes (FOC s ), which was paralleled by an increase in the systolic fura‐2 transient. In DCM, FOC f , FOC s 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 FOC f has been attributed to the Frank‐Starling mechanism, whereas FOC s represents a length‐dependent increase in the intracellular Ca 2+ ‐transient, the impaired length‐dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca 2+ ‐sensitivity as well as the intracellular Ca 2+ ‐homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end‐stage heart failure.