Indomethacin-induced scar thinning after experimental myocardial infarction.

Abstract

SUMMARY We investigated the effect of indomethacin, a widely used nonsteroidal antiinflammatory drug, on the healing of myocardial infarction (MI). Experimental MI was produced in anesthetized, openchest dogs by occluding the left anterior descending coronary artery. Ten dogs received indomethacin, 10 mg/kg i.v., and 11 received saline, 15 minutes and 3 hours after occlusion. After 6 weeks, the dogs were killed and their hearts were subjected to morphologic and biochemical analysis. The After lidocaine, 1.5 mg/kg i. v., was administered, the left anterior descending coronary artery was permanently occluded with a silk ligature. A second, similar dose of lidocaine was administered 5 minutes after occlusion in all dogs. The first seven dogs served as controls and received saline. (These dogs also served as controls in another study. 8) The rest of the dogs were randomized by drawing lots into two groups, six saline and 13 indomethacin, and the investigators were blinded as to which agent the dog received until all scar measurements had been completed. The control dogs received 50 ml of saline infused over 5 minutes. The other 13 dogs received indomethacin (Sigma Chemical Company) (10 mg/kg i.v.) in 50 ml of normal saline infused over 5 minutes, at 15 minutes and 3 hours after occlusion (total dose of 20 mg/kg). This dose of indomethacin was used because it was similar to that used by other investigators to ensure complete inhibition of prostaglandin synthesis in the cardiac vascular bed.9' '°All agents were infused through a peripheral vein. The chest was closed, the air was evacuated from the thoracic cavity and the dogs were returned to the kennel. One dose of benzanthine penicillin, 1.2 million units, was given intramuscularly to each dog.After 6 weeks, the dogs were reanesthetized with pentobarbital, 30 mg/kg i.v., killed with an overdose

Cyclooxygenase-2 Inhibition Increases Mortality, Enhances Left Ventricular Remodeling, and Impairs Systolic Function After Myocardial Infarction in the Pig

“…Several of the traditional nonsteroidal antiinflammatory drugs, inhibitors of both COX-1 and COX-2, have been shown to enhance LV dilatation and infarct expansion after experimentally induced MI. [5][6][7] Administration of these drugs to patients after MI may lead to the formation of ventricular aneurysms and ruptures. Low-dose aspirin promotes perivascular and interstitial fibrosis but does not alter infarct collagen content, cardiac dimensions, or function after MI in rats.…”

Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration

“…Although this inflammatory response may injure myocardial cells that would otherwise survive the ischemic episode (2), it also has a reparative function (3,4). Suppression of this host response impairs scar formation and may result in the formation of ventricular aneurysms (5)(6)(7)(8). Neutrophils initially predominate after reperfusion (9,10), but the proportion of monocytes in these infiltrates increases progressively with time (11).…”

Post-Infarction Inflammation and Left Ventricular Remodeling

“…58, 59 These findings suggest that inflammation during the acute phase of MI is essential for the healing process that follows, and complete suppression of inflammation after infarction may lead to an adverse outcome. However, in an experiment in which a large dose of dexamethasone was administered before ischemia in a mouse IR model, favorable results were reported: adhesion of neutrophils to the vascular endothelium was inhibited, endothelial nitric oxide synthase was activated, and the infarct was smaller.…”