Ventricular remodeling without cellular contractile dysfunction

Inder S. Anand

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: A number of factors may contribute to progressive left ventricular (LV) remodeling and global LV dysfunction after myocardial damage. Important among these are loss of myocytes from necrosis or apoptosis, changes in the extracellular matrix (ECM), myocyte contractile dysfunction, and the purely geometric or mechanical effects of structural alterations in the LV. Which of these components is more important at a particular stage in the natural history of LV remodeling is unclear. Nor is it known whether global LV dysfunction can occur in the absence of isolated myocyte contractile dysfunction. Methods and Results: We studied the natural history of LV remodeling in the rat infarct model to address the question of whether structural alterations in the heart can contribute directly to LV dysfunction or whether the presence of myocyte contractile dysfunction is essential for the development of systolic LV dysfunction, Over 6 weeks, post-MI rats developed progressive LV remodeling and dysfunction, with alterations in several biochemical markers such as a decrease in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and an increase in brain natriuretic peptide (BNP) and Na+-Ca2+ exchanger. Myocytes isolated from the remote noninfarcted LV of the remodeled hearts were hypertrophied. Changes in length of the remodeled myocytes correlated well with indices of global LV remodeling. However, no significant defects were seen in any of the contractile or intracellular calcium transient parameters of the remodeled myocytes in the unloaded state, after viscous loading or during increased stimulation frequency. Conclusions: These data suggest that myocyte hypertrophy may be dissociated from myocyte contractile defect and that global LV systolic dysfunction can occur in the absence of significant myocyte contractile dysfunction. Factors such as loss of muscle mass from necrosis or apoptosis, increased wall stress, and alterations in the ECM may play a more important role early in the natural history of LV remodeling, before myocyte contractile dysfunction has become apparent.

Original languageEnglish (US)
Pages (from-to)S401-S408
JournalJournal of cardiac failure
Volume8
Issue number6 SUPPL.
DOIs
StatePublished - Dec 2002

Keywords

  • Extracellular matrix
  • LV function
  • Ventricular remodeling

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