Idiopathic dilated cardiomyopathy was associated with extensive remodeling of the t-tubular network, shifting the median t-tubule angle from 95 degrees in normal hearts to 57 degrees.
Cross-Sectional (n=11)
No
Absolute Event Rate: 57% vs 95%
p-value: p=<0.001
BACKGROUND: The cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure. METHODS AND RESULTS: The organization of t-tubules, L-type calcium channels (DHPRs), ryanodine receptors (RyRs) and contractile machinery were examined in fixed ventricular tissue samples from both normal and failing hearts (idiopathic (non-ischemic) dilated cardiomyopathy) using high resolution fluorescent imaging. Wheat germ agglutinin (WGA), Na-Ca exchanger, DHPR and caveolin-3 labels revealed a shift from a predominantly transverse orientation to oblique and axial directions in failing myocytes. In failure, dilation of peripheral t-tubules occurred and a change in the extent of protein glycosylation was evident. There was no change in the fractional area occupied by myofilaments (labeled with phalloidin) but there was a small reduction in the number of RyR clusters per unit area. The general relationship between DHPRs and RyR was not changed and RyR labeling overlapped with 51±3% of DHPR labeling in normal hearts. In longitudinal (but not transverse) sections there was an ∼30% reduction in the degree of colocalization between DHPRs and RyRs as measured by Pearson's correlation coefficient in failing hearts. CONCLUSIONS: The results show that extensive remodelling of the t-tubular network and associated excitation-contraction coupling proteins occurs in failing human heart. These changes may contribute to abnormal calcium handling in heart failure. The general organization of the t-system and changes observed in failure samples have subtle differences to some animal models although the general direction of changes are generally similar.
Crossman et al. (Wed,) conducted a cross-sectional in Idiopathic dilated cardiomyopathy (n=11). Idiopathic dilated cardiomyopathy vs. Normal heart tissue was evaluated on Median angle of t-tubules relative to the cell surface (p=<0.001). Idiopathic dilated cardiomyopathy was associated with extensive remodeling of the t-tubular network, shifting the median t-tubule angle from 95 degrees in normal hearts to 57 degrees.