Remodeling after myocardial infarction in humans is not associated with interstitial fibrosis of noninfarcted myocardium

Department of Cardiovascular Pathology, University of Amsterdam, The Netherlands.

OBJECTIVES: This study was specifically designed to evaluate whether noninfarcted hypertrophic myocardium in patients with end-stage heart failure after myocardial infarction (MI) is associated with an increase in interstitial fibrous tissue. BACKGROUND: Postinfarction remodeling consists of complex alterations that involve both infarcted and noninfarcted myocardium. The question arises whether ventricular dysfunction is due to physical events, such as inadequate myocardial hypertrophy to compensate for increased tangential wall stress, or is caused by the development of progressive interstitial fibrosis in noninfarcted myocardium. METHODS: Fifteen hearts were obtained as cardiac explants (n = 13) or at autopsy (n = 2) from patients with end-stage coronary artery disease. Sixteen normal hearts served as reference hearts. Samples were taken from the left ventricular (LV) wall that contained the infarcted area, the border area and noninfarcted myocardium remote from scar areas. Collagen was quantified biochemically and microdensitophotometrically. Collagen type I and III ratios were analyzed by using the cyanogen bromide method and immunohistochemical staining, followed by microdensitophotometric quantification. RESULTS: In noninfarcted myocardium remote from the scar areas, total collagen levels and collagen type I/III ratios did not differ statistically from those in reference hearts. These observations contrasted with high total collagen content and high collagen type I/III ratios in scar and border areas. CONCLUSIONS: Remodeling of LV myocardium after MI in patients with end-stage heart failure is not necessarily associated with interstitial fibrosis in noninfarcted hypertrophic myocardium remote from scar areas. This finding raises questions regarding therapeutic interventions designed to prevent or retard the development of interstitial fibrosis.

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