Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat

Abstract

The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardium, was undertaken to address these issues. Collagen volume fraction (trichrome), fibrillar collagens (picrosirius-polarisation technique), and the stress-strain relations of the intact myocardium (isolated hearts) were determined 30 d after the infusion of microspheres into the left ventricle. Significant differences from controls included: (a) the presence of hypertension secondary to renovascular embolisation; (b) a greater volume fraction of collagen that included not only a meshwork of short, taut appearing, thick and thin collagen fibres, interposed between muscle in areas of cell loss, but also a perivascular fibrosis involving intramyocardial coronary arteries; (c) elevated active stiffness, and (d) a more exponential diastolic stress-strain relation with increased stiffness at strains of 5% or more. These findings suggest that the replacement fibrosis accompanying myocyte necrosis has distinguishing morphological features involving fibrillar collagen and which because of its structure, alignment, and location relative to muscle leads to enhanced myocardial stiffness, including a more exponential rise in the diastolic stress-strain relation. The perivascular accumulation of collagen suggests that additional factors other than microsphere induced necrosis were responsible for this reactive fibrosis.

Aldosterone and Myocardial Fibrosis in Heart Failure

“…Such pronounced perimuscular fibrosis may reduce myocyte generated force causing a progressive atrophy of myocytes [33]. The functional consequence is a downward shift of the systolic stress-strain relationship together with a marked elevation in diastolic stiffness [19]. Thus, combined diastolic/systolic dysfunction of the left ventricle appears in this late remodeling stage of hypertensive heart disease [18,59].…”

Angiotensin and the remodelling of the myocardium.

“…The functional consequences of these various patterns of myocardial fibrosis have been examined in the rat (Carroll et al, 1989;Doering et al, 1988;Jalil et al, 1989a,b). The findings of these studies emphasize the importance of collagen fibre configuration, alignment, and location (see Figure 3) on myocardial stiffness and myocyte loading.…”

Long-Term Changes in Collagen Formation Expressed by Serum Carboxyterminal Propeptide of Type-I Procollagen and Relation to Left Ventricular Function after Acute Myocardial Infarction

“…The repair processes following myocardial necrosis involve collagen deposition, and the extent and quality of repair are believed to affect the LV remodeling following AMI [6, 7, 8, 9]. Type-I and -III collagen are the major fibrillar components of the myocardial extracellular matrix and are known to be involved in the healing process after AMI [10, 11, 12].…”