An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.

Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.

Angina/Non-ST-Elevation Myocardial Infarction : ACC/AHA 2007 Guidelines for the Management of Patients With Unstable ISSN: 1524-4539 Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX doi: 10.1161/CIRCULATIONAHA.107.18194

https://cdr.lib.unc.edu/downloads/vd66w2108

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction)...

1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)

Background—The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contras...

Prognostic Significance of Microvascular Obstruction by Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction

http://www.mmh.org.tw/taitam/car_int/Documents/amipdf99edits.pdf

ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction

Etude faite chez le chien. Les doses eleves de methylprednisolone, mais pas les doses faibles, provoquent une cicatrice nettement moins epaisse, avec reduction de la fonction regionale, sans modification du contenu en collagene

Dose-dependent effects of short-term methylprednisolone on myocardial infarct extent, scar formation, and ventricular function.

Although much attention has been directed toward interventions which reduce myocardial infarct size, the effect of such agents on the healing phase of myocardial infarction is not well understood. The present study examines the effect of the nonsteroidal anti-inflammatory agent ibuprofen, previously demonstrated to be able to reduce infarct size, and of aspirin on the healing of experimentally produced myocardial infarcts. Thirty-nine anesthetized, open-chest dogs were subjected to proximal left anterior descending coronary artery occlusions for 6 weeks. Four groups of dogs were studied: (1) a control (untreated) group: (2) ibuprofen, 12.5 mg/kg intravenously 15 minutes and 6, 12, 18, and 24 hours after occlusion (high dose); (3) ibuprofen, 12.5 mg/kg intravenously 15 minutes and 3 hours after occlusion (low dose); (4) aspirin, 30 mg/kg intravenously 15 minutes and 3 hours after occlusion. The average thickness of the transmural scar and of the noninfarcted left ventricular wall was determined from multiple measurements of formalin-fixed left ventricular slices. The ratio of transmural scar to noninfarcted wall thickness was determined. In control animals the ratio was 0.87 with only 1 of 15 animals having a ratio

Scar thinning due to ibuprofen administration after experimental myocardial infarction.

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, open-chest 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 average thickness of the transmural scar and the noninfarcted left ventricular wall was measured at multiple sites in formalin-fixed left ventricular slices and the ratio of the thickness of the transmural scar to the noninfarcted wall determined. The average thickness of the noninfarcted wall was 8.80 +/- 0.19 mm (mean +/- SEM) in the control group and 8.44 +/- 0.26 mm in the indomethacin group (NS). The scar thickness was 7.24 +/- 0.64 mm in the control group and 3.56 +/- 0.40 mm in the indomethacin group (p less than 0.001). The ratio of scar to noninfarcted wall thickness was 0.83 +/- 0.07 in the control group and 0.43 +/- 0.04 in the indomethacin group (p less than 0.001). Scars in treated dogs did not differ from controls either by light microscopic histologic analysis or by analysis of hydroxyproline content per unit weight. We conclude that indomethacin results in marked scar thinning when given early after experimental MI.

Indomethacin-induced scar thinning after experimental myocardial infarction.

Enhancement of salvage of reperfused myocardium by early beta-adrenergic blockade (timolol).

It has been established that glucocorticoids and several nonsteroidal antiinflammatory drugs, when administered early after coronary occlusion, interfere with myocardial scar formation. To determine whether this action is associated with expansion of myocardial infarct during the first week of coronary occlusion and whether expansion affects ventricular function, the effects of indomethacin on the left ventricle in the early phase of infarction were studied. In a blinded randomized study, experimental myocardial infarction was produced in 17 open-chest dogs by ligation of the proximal left anterior descending coronary artery; the treated group (n = 8) received 10 mg/kg iv indomethacin at 15 min and 3 hr after occlusion, and the control group (n = 9) received saline. After 7 days, regional function expressed as percent change of area (% delta A) of the left ventricular cavity was calculated from short-axis two-dimensional echocardiograms at the level of the infarct, the animals were killed, and their heart...

Haim Hammerman

Papers

Dose-dependent effects of short-term methylprednisolone on myocardial infarct extent, scar formation, and ventricular function.

Scar thinning due to ibuprofen administration after experimental myocardial infarction.

Indomethacin-induced scar thinning after experimental myocardial infarction.

Enhancement of salvage of reperfused myocardium by early beta-adrenergic blockade (timolol).

Drug-induced expansion of infarct: morphologic and functional correlations.