Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

Abstract

Cardiomyocyte dedifferentiation, as detected in hibernating myocardium of chronic ischemic patients, is one of the characteristics seen at the border of myocardial infarcts in small and large animals. Our objectives were to study in detail the morphological changes occurring at the border zone of a rabbit myocardial infarction and its use as model for hibernating myocardium. Ligation of the left coronary artery (LAD) was performed on rabbit hearts and animals were sacrificed at 2, 4, 8 and 12 weeks postinfarction. These hearts together with a non-infarcted control heart were perfusion-fixed and tissue samples were embedded in epoxy resin. Hibernating cardiomyocytes were mainly distributed in the non-infarcted region adjacent to the border zone of infarcted myocardium but only in a limited number. In the border zone itself vacuolated cardiomyocytes surrounded by fibrotic tissue were frequently observed. Ultrastructural analysis of these vacuolated cells revealed the presence of a basal lamina inside the vacuoles adjacent to the surrounding membrane, the presence of pinocytotic vesicles and an association with cisternae of the sarcoplasmatic reticulum. Myocyte quantitative analyses revealed a gradual increase in vacuolar area/total cell area ratio and in collagen fibril deposition inside the vacuoles from 2 to 12 weeks post-infarction. Related to the remote zone, the increase in cell width of myocytes located in and adjacent to the border zone demonstrated cellular hypertrophy. These results indicate the occurrence of cardiomyocyte remodelling mechanisms in the border zone and adjacent regions of infarcted myocardium. It is suggested that the vacuoles represent plasma membrane invaginations and/or dilatations of T-tubular structures.

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

“…T-system remodeling in failing rodent hearts has been studied extensively, but t-system components as found in human heart failure or in a porcine infarct model (Pinali et al, 2017) have not been identified. In contrast, images of remodeled t-tubules published by others (Driesen et al, 2007) and us (Seidel et al, 2016), including the present study, indicate that t-system remodeling in rabbit resembles the human phenotype. Driesen et al described vacuole-like structures in cardiomyocytes adjacent to the infarct border in rabbit and suggested that “the vacuoles represent plasma membrane invaginations and/or dilatations of t-tubular structures.” Based on our three-dimensional reconstructions (Fig.…”

T-tubule remodelling disturbs localized β2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure

“…HF has been shown to be accompanied by cardiomyocyte dedifferentiation and a reactivation of the fetal gene programme 39 . Therefore, the structural remodelling observed may also reflect a return to a more ‘fetal phenotype’.…”

Dedifferentiation and Proliferation of Mammalian Cardiomyocytes

“…Dedifferentiated myocytes flatten and spread out in culture [45], [46]; sarcomeres become ill-defined and disorganized, and the expression of contractile proteins is dramatically altered [47], [48]. Phenomena akin to in vitro dedifferentiation have also been described in vivo , in fibrillating atria [49], in chronically-ischemic myocardium, and in the border zone of myocardial infarcts [50]. Such dedifferentiated myocytes are not apoptotic and presumably reflect adaptations to abnormal myocardial stress and/or perfusion [51].…”