Inflammatory Activity in Sympathetic (Stellate) Ganglia of Patients with Life Threatening Cardiac Arrhythmias.
Stefania Rizzo, Dirk Troost, Cristina Basso, Gaetano Thiene, Antoine Driessen, Arthur A Wilde, Allard C van der Wal. University of Padua, Italy; Academic Medical Center, University of Amsterdam, Netherlands
Background: Long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are electrical diseases of the heart characterized by episodes of life threatening arrhythmias. The pathogenesis of these inherited diseases is complex; a link to autonomic imbalance has been established, possibly as an epiphenomenon that could relate to exaggerated symptomatology. Stellate ganglion excision is a therapeutic modality in those LQTS/CPVT patients with arrhythmias that are resistant to pharmacological drugs. We investigated potential inflammatory/degenerative pathology in stellate ganglia of LQTS/CPVT patients with intractable arrhythmias.
Design: Surgically excised stellate ganglia were retrieved from 10 patients (7F, 3M, mean age 20.7±15.5 yrs) with either LQTS (n=5) or CVPT (n=5). Control stellate ganglia were obtained from 4 accidently (traumatic) deceased patients (1F, 3M, mean age 20.5±3.8 yrs). Sections were immunostained with antibodies anti S100, CD3 (pan T-cell), CD8 (cytotoxic T-cells, CTL's) Granzyme B (activated CTL's), CD20 (B-cells), and CD68 (macrophages) and MHC class II antigens. The inflammatory process was semiquantitatively graded as 0 (normal), 1 (individual inflammatory cells), 2 (inflammatory cells without ganglionits) and 3 (clustering of inflammatory cells and ganglionitis).
Results: Stellate ganglia of LQTS/CVPT patients revealed microscopic foci of score 2-3 inflammation in all cases. The infiltrates were composed of macrophages (CD68+) and T cells (CD3+) which were predominantly CD8+, Granzyme+ CTL's. B-cells were sparse. In addition, all cases showed T-lymphocytes surrounding the cytoplasm of one or more ganglion cells in combination with HLA-DR positivity, interpreted as low grade inflammatory-mediated destruction of ganglion cells (ganglionitis). Control ganglia of accidental deaths showed at maximum a mild inflammatory infiltrate (score 0-1) with sparse CD8+ T cells.
Conclusions: Our findings indicate a low grade CTL-mediated ganglionitis in the stellate ganglia of severely symptomatic LQTS/CVPT patients. Production of inflammatory cytokines and a sympathetic stress response could favour cardiac electrical instability in these patients genetically predisposed to arrhythmias.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 42, Wednesday Afternoon