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Mast cell stabilization decreases cardiomyocyte and LV function in dogs with isolated mitral regurgitation

Betty Pat1, Cheryl Killingsworth, Yuanwen Chen

  • 1Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.

Journal of Cardiac Failure
|August 28, 2010
PubMed
Abstract

Insights

Mast cell stabilization did not prevent left ventricular remodeling in dogs with mitral regurgitation. This therapy worsened heart function due to direct negative effects on cardiomyocytes.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Cell Biology

Background:

  • Mast cells increase in isolated mitral regurgitation (MR), potentially causing extracellular matrix loss and left ventricular (LV) dilation.
  • The study investigated the role of mast cells in MR-induced cardiac remodeling and function.

Purpose of the Study:

  • To test if mast cell stabilization attenuates LV remodeling and improves function in a canine model of MR.
  • To evaluate the direct effects of mast cell stabilizers on cardiomyocyte function.

Main Methods:

  • Mitral regurgitation (MR) was induced in dogs, randomized to no treatment or ketotifen (mast cell stabilizer) for 4 months.
  • Left ventricular (LV) hemodynamics and cardiac magnetic resonance imaging (MRI) were performed.
  • In vitro studies assessed ketotifen's effect on normal cardiomyocytes.

Main Results:

  • Both MR and MR + mast cell stabilizer groups showed increased LV volumes and decreased interstitial collagen compared to normal dogs.
  • LV contractility and cardiomyocyte fractional shortening were depressed in MR dogs and further worsened by mast cell stabilization.
  • Ketotifen directly reduced fractional shortening and calcium transients in normal cardiomyocytes.

Conclusions:

  • Chronic mast cell stabilization did not prevent eccentric LV remodeling or collagen loss in MR.
  • Mast cell stabilization therapy negatively impacted LV function due to a direct negative inotropic effect on cardiomyocytes.

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