Diastolic dysfunction in hypertrophic cardiomyopathy: Effect on active force generation during systole

Judith K. Gwathmey, Sanford E. Warren, G. Maurice Briggs, Linda Copelas, Marc D. Feldman, Preston J. Phillips, Mark Callahan, Frederick J. Schoen, William Grossman, James P. Morgan

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

We tested the hypothesis that intracellular Ca++ ([Ca++]i]) over-load underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy. Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease. The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and |Ca++], was measured with the bioluminescent calcium indicator aequorin. In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components. At 38°C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared to develop, which produced a rise in end-diastolic [Ca++]I, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development. We also found that drugs which increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them. These results may explain why patients with hypertrophie cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophie cardiomyopathy. (J. Clin. Invest. 1991, 87:1023-1031.).

Original languageEnglish (US)
Pages (from-to)1023-1031
Number of pages9
JournalJournal of Clinical Investigation
Volume87
Issue number3
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Calcium indicators
  • Cyclic adenosine monophosphate
  • Diastolic dysfunction, hypertrophic cardiomyopathy
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Medicine(all)

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