Chronic Aspirin Treatment Affects Collagen Deposition in Non-infarcted Myocardium During Remodeling after Coronary Artery Ligation in the Rat

Abstract

Low-dose aspirin (acetylsalicylic acid; ASA), inhibiting platelet thromboxane production in favor of endothelium formation of prostaglandins, is successfully used as primary or secondary prophylaxis against myocardial infarction. Although prognosis may be improved, effects of long-term ASA treatment on wound healing and cardiac remodeling are not well understood. The aim of the present study was to mimic the clinical situation by inducing myocardial infarction in low-dose ASA (25 mg/kg/day, i.p.) pretreated rats, and to determine effects on plasma eicosanoid levels, cardiac hypertrophy and collagen deposition, and left ventricular function during continued ASA treatment. The effects of this dose were verified to selectively inhibit platelet thromboxane production, and lower plasma levels of thromboxane, but did not affect plasma levels of prostacyclin and prostaglandin E2 during the acute inflammatory stage following myocardial infarction. As measured by heart dry weight/body weight, cardiac hypertrophy was not affected by ASA treatment. However, interstitial fibrosis in the spared myocardium as well as perivascular fibrosis, associated with infarction-induced cardiac remodeling, were affected by ASA treatment. Replacement fibrosis in the infarct itself, considered as representing wound healing, was not significantly influenced by ASA treatment. Wall thinning following infarction was not aggravated, nor did treatment influence left ventricular cavity diameter in a relaxed state. Results from in vitro left ventricular function measurements showed no effects on left ventricular peak velocity of contraction or relaxation after ASA treatment. In conclusion, although low-dose ASA may not be expected to have anti-inflammatory action, it did influence post-infarct cardiac remodeling by affecting interstitial and perivascular fibrosis. ASA treatment did not have effects on in vitro left ventricular dysfunction.

Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen

“…Other investigators have stated that perivascular, and in particular periarterial, fibrosis does not play a significant role in the regulation of maximal myocardial perfusion in post-MI hearts (13,17,24,29). This assumption is based on two lines of experimental evidence.…”

“…Support for this supposition can be found in the earlier observations of Gervais et al (10), who showed that in young infarcted rats in which hypertrophy had been prevented but myocardial fibrosis had been allowed to develop naturally, perfusion within the surviving LV myocardium was not fully restored. On the basis of this accumulating evidence, we hypothesized that in infarcted middle-aged rats the extent of perivascular fibrosis may affect myocardial perfusion.Although there have been reports indicating that fibrosis of coronary arteries does not contribute to the regulation of myocardial perfusion in infarcted rats (13,17,24,29), the effects of fibrosis in the coronary arterioles has never been evaluated. Thus we designed our current study to investigate whether the extent of periarteriolar collagen is a factor in maximal myocardial perfusion in infarcted middle-aged rats in which adaptive arteriolar growth occurs in response to chronic HRR.…”

“…Although there have been reports indicating that fibrosis of coronary arteries does not contribute to the regulation of myocardial perfusion in infarcted rats (13,17,24,29), the effects of fibrosis in the coronary arterioles has never been evaluated. Thus we designed our current study to investigate whether the extent of periarteriolar collagen is a factor in maximal myocardial perfusion in infarcted middle-aged rats in which adaptive arteriolar growth occurs in response to chronic HRR.…”

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

“…atherosclerotic rodent model (28). The decrease in collagen content may contribute to the enhanced bioavailability of the free radical gas, NO.…”

Effects of erythropoietin on advanced pulmonary vascular remodelling

“…Sections were weighed separately and fixed in 3.6% formalin. De-paraffinised 5-mm thick transverse cardiac sections at midventricular level were stained with Gomori silver staining for analysis of myocyte size, and with Griffonia simplicifolia lectin staining (Sigma Chemical Co.) of endothelial cells for analysis of capillary density [13,14]. Image analysis (Image-Pro Plus 4.5) was used to measure capillary density and myocyte size.…”