Altered cardiac collagen and associated changes in diastolic function of infarcted rat hearts

Objective: Anti-inflammatory drugs have been shown to modulate collagen dep osition during myocardial infarction (MI) induced remodeling. Chronic effec ts of methylprednisolone (5 mg/kg/day) and low-dose aspirin (25 mg/kg/day) on cardiac collagen and left ventricular diastolic function were studied in rat hearts. 21 days after MI. Methods: Left ventricular function was asses sed at baseline and after P-adrenergic stimulation with isoproterenol in is olated perfused hearts, using an intraventricular balloon. After diastolic arrest, left ventricular pressure-volume curves were obtained. Left ventric ular dilation was defined as the corresponding left ventricular volume at 2 0 mmHg left ventricular diastolic pressure. In histological sections, periv ascular and interstitial collagen content were quantified morphometrically as the Sirius Red positive area in the non-infarcted interventricular septu m. Results: Impaired baseline left ventricular function of MI-hearts was im proved by methylprednisolone but not by low-dose aspirin. Isoprotenerol sig nificantly enhanced systolic function in all hearts. whereas it augmented t he decrease in left ventricular diastolic pressure only in methylprednisolo ne-treated MI-hearts. The rightward shift of the pressure-volume curve afte r MI was aggravated by methylprednisolone but not with low-dose aspirin tre atment. Low-dose aspirin reduced perivascular but not interstitial collagen whereas methylprednisolone decreased both perivascular and interstitial co llagen. Conclusions: Our findings indicate that MI-induced collagen deposit ion in the spared myocardium can be affected by chronic therapy with low-do se aspirin or methylprednisolone. The effects on interstitial collagen seem ed reflected in an altered left ventricular diastolic function. (C) 2000 El sevier Science B.V. All rights reserved.