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European Journal of Heart Failure 2005 7(1):29-35; doi:10.1016/j.ejheart.2004.03.018
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© 2004 European Society of Cardiology

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

Klara Brixiusa, Hannes Reutera, Wilhelm Blochb and Robert H.G. Schwingera,*

a Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III Joseph-Stelzmann-Str. 9, 50924 Cologne (Lindenthal), Germany
b Institute of Zellular and Molecular Sport Medicine, German Sport University Cologne, Germany

* Corresponding author. Tel.: +49-221-478-3138; fax: +49-221-478-3746. E-mail address: Robert.Schwinger{at}medizin.uni-koeln.de


  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.

Key Words: Calcium • Heart failure • Contraction • Myocardium

Received September 20, 2003; Revised March 5, 2004; Accepted March 10, 2004


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