Abstract
Adverse left ventricular (LV) remodeling after acute myocardial infarction is characterized by LV dilatation and development of a fibrotic scar, and is a critical factor for the prognosis of subsequent development of heart failure. Although myofiber organization is recognized as being important for preserving physiological cardiac function and structure, the anatomical features of injured myofibers during LV remodeling have not been fully defined. In a mouse model of ischemia–reperfusion (I/R) injury induced by left anterior descending coronary artery ligation, our previous histological assays demonstrated that broad fibrotic scarring extended from the initial infarct zone to the remote zone, and was clearly demarcated along midcircumferential myofibers. Additionally, no fibrosis was observed in longitudinal myofibers in the subendocardium and subepicardium. However, a histological analysis of tissue sections does not adequately indicate myofiber injury distribution throughout the entire heart. To address this, we investigated patterns of scar formation along myofibers using three‐dimensional (3D) images obtained from multiple tissue sections from mouse hearts subjected to I/R injury. The fibrotic scar area observed in the 3D images was consistent with the distribution of the midcircumferential myofibers. At the apex, the scar formation tracked along the myofibers in an incomplete C‐shaped ring that converged to a triangular shape toward the end. Our findings suggest that myocyte injury after transient coronary ligation extends along myofibers, rather than following the path of coronary arteries penetrating the myocardium. The injury pattern observed along myofibers after I/R injury could be used to predict prognoses for patients with myocardial infarction.
Highlights
Adverse left ventricular (LV) remodeling is a common occurrence following acute myocardial infarction (MI), and an important factor in determining the prognosis for subsequent development of heart failure (Pfeffer and Braunwald 1990)
The smooth transition in CM size throughout the LV wall is consistent with previous reports shown by diffusion tensor-magnetic resonance imaging (DT-MRI) (Sosnovik et al 2014), and suggests that changes in the CM and myofiber angle from the subendocardium to subepicardium were gradual with no abrupt changes or gaps
The pattern shown by the 3D image and higher magnification views of Masson’s trichrome staining strongly suggest that myocardial injury following I/R extends along myofibers, rather than along coronary arteries crossing the myocardium from the subepicardium to subendocardium
Summary
Adverse left ventricular (LV) remodeling is a common occurrence following acute myocardial infarction (MI), and an important factor in determining the prognosis for subsequent development of heart failure (Pfeffer and Braunwald 1990). LV enlargement and myocardial scarring are often discussed as key pathophysiological features in LV remodeling (Opie et al 2006). Pathological patterns of cardiac remodeling following I/R injury are not well characterized, except for the severity of injury (Yellon and Hausenloy 2007). Myofibers are formed from bundles of cardiomyocytes (CMs) surrounded by a perimysium (Anderson et al 2005). Advanced imaging systems, such as diffusion tensor-magnetic resonance imaging (DT-MRI), have revealed critical features of the architectural arrangement of myofibers in the LV mass of humans (Tseng et al 2000). Recent studies using DT-MRI demonstrated that myofiber structure is significantly disrupted in LV remodeling following acute MI (Sosnovik et al 2014). The pathophysiological features of myofibers in the heart resulting from ischemic heart diseases are not well characterized
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