Inhomogeneity of collagen organization within the fibrotic scar after myocardial infarction: results in a swine model and in human samples

Abstract

We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84-0.94); median (interquartile range)], epicardium [0.84 (0.79-0.91)] and peripheral area [0.73 (0.63-0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45-0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P < 0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction.

Interstitial changes after reperfused myocardial infarction in swine: morphometric and genetic analysis

“…Five controls and 15 MI experiments (without coronary reperfusion or followed by 1-week or 1-month reperfusion; n = 5 animals in each experimental group) made up the final study group. A sample size of 5 swine in each experimental was based on previous literature not only from our group [ 13 , 14 ] and others [ 15 – 17 ].…”

Kinetic alterations of collagen and elastic fibres and their association with cardiac function in acute myocardial infarction

“…Following AMI, adjustment of collagen I/III fibre and elastic fibre composition determines cardiac function via ventricle wall compliance and tensile strength ( 12 ). An increase in the collagen I/III component augments heart stiffness, which subsequently aggravates left ventricular diastolic and systolic dysfunction ( 13 , 14 ). These previous findings are in accordance with the results of the present study, and collectively suggest that a compromised the function of the heart, resulting in reconstruction of heart configuration, leads to cardiac dysfunction and even heart failure.…”

Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization

“…Doillon and co-workers observed that the collagen distribution was poorly organized during wound healing in a full thickness defect in rat skin [10]. Furthermore, the group of Bodi showed that in swine, and more importantly in human, the collagen organization at the outer region of the myocardial infarcted area was more disorganized and random compared to the core region [11]. Other mechanical properties that changed during valvular ECM remodeling have been shown to affect VIC phenotypic change and functions, for example stress relaxation [12] and transvalvular pressure [13].…”