Remodeling of the transverse tubular system after myocardial infarction in rabbit correlates with local fibrosis: A potential role of biomechanics

The transverse tubular system (t-system) of ventricular cardiomyocytes is essential for efficient excitation-contraction coupling. In cardiac diseases, such as heart failure, remodeling of the t-system contributes to reduced cardiac contractility. However, mechanisms of t-system remodeling are incompletely understood. Prior studies suggested an association with altered cardiac biomechanics and gene expression in disease. Since fibrosis may alter tissue biomechanics, we investigated the local microscopic association of t-system remodeling with fibrosis in a rabbit model of myocardial infarction (MI). Biopsies were taken from the MI border zone of 6 infarcted hearts and from 6 control hearts. Using confocal microscopy and automated image analysis, we quantified t-system integrity (ITT) and the local fraction of extracellular matrix (fECM). In control, fECM was 18 ± 0.3%. ITT was high and homogeneous (0.07 ± 0.006), and did not correlate with fECM (R2 = 0.05 ± 0.02). The MI border zone exhibited increased fECM within 3 mm from the infarct scar (30 ± 3.5%, p