Chronic aspirin treatment affects collagen deposition in non-infarcted myocardium during remodeling after coronary artery ligation in the rat.
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.
Kalkman
E A
EA
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
van Suylen
R J
RJ
van Dijk
J P
JP
Saxena
P R
PR
Schoemaker
R G
RG
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism*; D003331:Coronary Vessels; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000097:blood; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005355:Fibrosis / Q000473:pathology; D006321:Heart / Q000187:drug effects*; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000096:biosynthesis; D016277:Ventricular Function, Left / Q000187:drug effects
D015777:Eicosanoids; D013931:Thromboxanes; D003094:Collagen; D011464:Epoprostenol; D001241:Aspirin