Altered cardiac collagen and associated changes in diastolic function of infarcted rat hearts.
OBJECTIVE
Anti-inflammatory drugs have been shown to modulate collagen deposition during myocardial infarction (MI) induced remodeling. Chronic effects 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 assessed at baseline and after beta-adrenergic stimulation with isoproterenol in isolated perfused hearts, using an intraventricular balloon. After diastolic arrest, left ventricular pressure-volume curves were obtained. Left ventricular dilation was defined as the corresponding left ventricular volume at 20 mmHg left ventricular diastolic pressure. In histological sections, perivascular and interstitial collagen content were quantified morphometrically as the Sirius Red positive area in the non-infarcted interventricular septum.


RESULTS
Impaired baseline left ventricular function of MI-hearts was improved by methylprednisolone but not by low-dose aspirin. Isoprotenerol significantly enhanced systolic function in all hearts, whereas it augmented the decrease in left ventricular diastolic pressure only in methylprednisolone-treated MI-hearts. The rightward shift of the pressure-volume curve after MI was aggravated by methylprednisolone but not with low-dose aspirin treatment. Low-dose aspirin reduced perivascular but not interstitial collagen whereas methylprednisolone decreased both perivascular and interstitial collagen.


CONCLUSIONS
Our findings indicate that MI-induced collagen deposition in the spared myocardium can be affected by chronic therapy with low-dose aspirin or methylprednisolone. The effects on interstitial collagen seemed reflected in an altered left ventricular diastolic function.
Van Kerckhoven
R
R
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands. vankerckhoven@farma.fgg.eur.nl
Kalkman
E A
EA
Saxena
P R
PR
Schoemaker
R G
RG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001158:Arteries / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism*; D003971:Diastole; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D020257:Ventricular Remodeling / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003094:Collagen; D007545:Isoproterenol; D001241:Aspirin; D008775:Methylprednisolone