Altered myocardial force-frequency relation in human heart failure

Louis A. Mulieri, Gerd Hasenfuss, Bruce Leavitt, Paul D. Allen, N. R. Alpert

Research output: Contribution to journalArticle

425 Scopus citations

Abstract

Background. In congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function. Methods and Results. The isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37°C and contraction frequencies ranging from 12 to 240 per minute (min-1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfailing myocardium the twitch tension-frequency relation is bell-shaped developing 25±2 mN/mm2 at a contraction frequency of 72 min-1 and peaking at 44±3.7 mN/mm2 at a contraction frequency of 174±4 min-1. In failing myocardium the peak of the curve occurs at lower frequencies between 6 and 120 min-1 averaging 81±22 min-1, and it develops 48% (p<0.001) and 80% (p<0.001) less tension than in nonfailing myocardium at 72 and 174 min-1, respectively. Between 60 and 150 min-1 tension increases by 107% in nonfailing myocardium, but it does not change significantly in failing myocardium. Peak rates of rise and fall of isometric twitch tension vary in parallel with twitch tension as stimulation frequency rises in nonfailing myocardium but not in failing myocardium. Conclusions. The quantitative agreement between these results from isolated myocardium and those from catheterization laboratory measurements on intact humans suggest that alterations of myocardial origin, independent of systemic factors, may contribute to the above mentioned abnormalities in left ventricular function seen in dilated cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)1743-1750
Number of pages8
JournalCirculation
Volume85
Issue number5
StatePublished - May 1992
Externally publishedYes

Keywords

  • Force-frequency relation
  • Idiopathic dilated cardiomyopathy
  • Myocardial twitch tension
  • Tachycardia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Mulieri, L. A., Hasenfuss, G., Leavitt, B., Allen, P. D., & Alpert, N. R. (1992). Altered myocardial force-frequency relation in human heart failure. Circulation, 85(5), 1743-1750.