Purpose: Fibrosis plays a key role in the pathophysiology of left ventricular (LV) remodelling after myocardial infarction (MI). The dynamics of this process and whether it is a localized or diffuse phenomenon has not been totally clarified. We aimed to characterize these issues in a swine model of reperfused anterior MI.
Methods: Swine were subjected by means of percutaneous balloon inflation to a transient 90-min occlusion of mid left anterior descending artery followed by 72-h (acute MI model) or 1-month (chronic MI model) reperfusion. The extent of fibrosis was macroscopically (triphenyltetrazolium staining, % of LV volume) and microscopically (Sirius red staining, % of field) quantified in the infarct, adjacent and remote areas as well as in controls. TGF-β1, collagen1-A1, A2 and 3A1 gene expression was determined.
Results: Macroscopically, necrosis (16±5% in the acute MI model) and fibrosis (16±4% in the chronic MI model) were detected in all cases. Macroscopic fibrosis occurred in the infarct but not in the adjacent or remote areas (Figure). At microscopic level, in comparison with controls, fibrosis was only significantly increased in the chronic MI model at the infarct area (35±4%, p<0.001) but not in the acute MI model or in the adjacent and remote areas in the chronic MI model (<4% in all cases, p=ns, Figure). TGF-β1 (p<0.05, acute and chronic MI models, Figure) and collagen1-A1, A2 and 3A1 (p<0.001, chronic MI model) gene expression were significantly increased in the infarct but not in the adjacent or remote areas (p=ns).
Conclusion: In a model of anterior MI, 1-month after reperfusion, at macroscopic, microscopic and molecular levels, myocardial fibrosis appears as a localized process which mainly affects the infarct area but not the adjacent or remote regions.