Ultrastructural Remodeling of Cardiomyocytes in Postinfarction Myocardium of Rats in the Late Stages of the Disease

Cytometry A. 2024 Dec 31. doi: 10.1002/cyto.a.24915. Online ahead of print.

Abstract

Identifying factors that contribute to the transition to the dilated phase in cardiac ischemia is a critical challenge in heart failure treatment. Currently, no effective therapies exist for this ischemic complication, and the mechanisms driving left ventricular dilatation during chronic post-infarction remodeling remain poorly understood. One potential pathological process leading to ventricular dilatation involves specific compensatory rearrangements in the border zone adjacent to the infarct, which isolates the intact myocardium from inflammation at the scar edge. Using a rat model, we examined ultrastructural changes in the intact and border zones of post-infarction myocardium at chronic stages. Morphometric analysis of myofibrils, mitochondria, and excitation-contraction coupling structures revealed similar remodeling processes in both zones at 2 weeks post-infarction, characterized by decreased myofibril density, reduced mitochondrial area and volume density, and shortened contacts between T-tubules and sarcoplasmic reticulum. At 26 weeks post-infarction, during the dilated cardiomyopathy phase, we observed distinct compensatory changes in the border zone. Specifically, there was a loose arrangement of myofibrils and an increased volume fraction of mitochondria. These differences in remodeling between the intact and border zones highlight factors contributing to ventricular dilatation and help the development of new therapeutic strategies to delay heart failure progression in cardiac ischemia.

Keywords: T‐tubules; border zone; cardiomyocytes; late post‐infarction remodeling; mitochondria; morphometric analysis; myocardium infarction; sarcoplasmic reticulum.