Abstract 13813: Transmural Heterogeneity of Cellular Level Power Output is Reduced in Human Heart Failure
Background: Heart failure is associated with global pump dysfunction and ventricular remodeling. However, it is not known if different transmural regions of the left ventricular wall are affected in the same way. We tested the hypothesis that cellular level power output is heterogeneous in nonfailing left ventricle and that this transmural pattern is reduced in heart failure.
Methods and Results: Through-wall left ventricular samples were procured from organ donors with nonfailing hearts (n=6) and patients undergoing heart transplants with failing hearts (n=10). Mechanical assays were performed on chemically permeabilized multicellular preparations that were isolated from the epicardial, midmyocardial, and endocardial regions of the left ventricular free wall. Maximum power output, a cellular level measure of systolic function, was 25% lower (p=0.009) in samples from failing hearts (0.37 ± 0.02 μW mg-1) than in samples from nonfailing hearts (0.50 ± 0.03 μW mg-1). Furthermore, the samples from the midmyocardium of the nonfailing hearts produced significantly higher maximum power output than the samples from the endocardium and the epicardium. In contrast, there were no statistically significant transmural differences in power output in the failing samples. The transmural remodeling effects observed in these multicellular permeabilized cardiac preparations may be due to changes in interstitial and sarcomeric proteins. Histology revealed an increase in collagen in failing samples when compared to the nonfailing samples (p=0.021), suggesting replacement of myocytes with fibrotic tissue. The failing samples also exhibited lower phosphorylation of cardiac troponin I (p=0.011) and cardiac myosin binding protein-C (p=0.042), consistent with diminished β-adrenergic signaling effects.
Conclusions: Cellular level power output exhibited transmural heterogeneity in nonfailing hearts. This pattern was lost in failing hearts which may contribute to global pump dysfunction. Changes in collagen and posttranslational modifications to key sarcomeric proteins contribute to cellular level remodeling in human heart failure.
- © 2013 by American Heart Association, Inc.