Role of mast cells and their mediators in failing myocardium under mechanical ventricular support

Akgul, Ahmet; Skrabal, Christian A; Thompson, Larry O; Loebe, Matthias; Lafuente, Javier A; Noon, George P; Youker, Keith A

doi:10.1016/j.healun.2003.06.006

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 23, Issue 6 , Pages 709-715, June 2004

Role of mast cells and their mediators in failing myocardium under mechanical ventricular support☆

Ahmet Akgul, MD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
Christian A Skrabal, MD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
Larry O Thompson, MD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
Matthias Loebe, MD, PhD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
Javier A Lafuente, MD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
George P Noon, MD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
Keith A Youker, PhD
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
- Reprint requests: Keith A. Youker, PhD, Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Telephone: 713-798-4188. Fax: 713-796-0015.

Received 17 December 2002; received in revised form 6 June 2003; accepted 12 June 2003.

Abstract

Background

Mast cells have been implicated in tissue remodeling and fibroblast stimulation. We explored the effect of mechanical support by left ventricular assist device (LVAD) in failing myocardium and looked into grade and distribution of interstitial fibrosis, mast cell density, mast cell phenotypes and basic fibroblast growth factor (bFGF) expression pre- and post-LVAD.

Methods

Myocardial tissue was obtained from 20 patients with end-stage cardiomyopathy at the time of LVAD implantation and LVAD removal and from 7 donor hearts not used for transplantation. Tissue sections were stained for mast cells using tryptase as a marker and the myocardial fibrosis was measured. Double staining for tryptase and chymase was performed for detection of chymase-positive mast cells. Fluorescent microscopy showed the relationship of mast cells to bFGF, and bFGF expression was quantified by Western blot.

Results

There was a significant increase in mast cells in heart failure vs normal myocardium. A secondary increase in mast cells occurred after long-term (>40 days) support compared with matched pre-LVAD samples (mean ± SEM; 57.4 ± 8.6 cells/10 fields vs 45.1 ± 7.6 SEM cells/10 fields, p < 0.01). The secondary increase in mast cells was associated specifically with an increase in chymase-negative mast cells (p < 0.01). These findings are statistically significant with concurrent decreased expression of bFGF and decreased fibrosis in the same patient tissues (p < 0.01).

Conclusions

We suggest that, under long-term support, there is a change in phenotypic expression in mast cells, which can alter fibroblast functions. The decreased myocardial bFGF levels might be the result of these phenotypically altered mast cells.