ISCHEMIC HEART DISEASE is the major etiology for heart failure today (3). The initial event is frequently a large or recurrent myocardial infarction. Acute myocardial infarction starts with thrombotic occlusion of a coronary artery, develops during several hours, and terminates when necrosis has reached its ultimate extension, which is defined by the boundary of the infarct-associated vascular bed and potential collateral flow. Therapy of acute myocardial infarction is reasonably standardized and consists of prevention of fatal arrhythmias and early reperfusion, for instance, by vessel dilatation and stent implantation, to limit infarct size. If reperfusion is established too late, large transmural infarction may develop that results in a reduction of left ventricular function and is followed by “remodeling” of the heart (Fig. 1). Remodeling is closely related to “infarct expansion,” which may continue after the necrosis has extended to its ultimate size; the left ventricle dilates, probably because of increased wall stress on the basis of La Place’s law (1). The increase in global left ventricular volume indicates and quantifies remodeling of the heart, which may ultimately result in heart failure, arrhythmias, and sudden death (8). Standard therapy today tries to prevent remodeling and its prognostic consequences by reducing cardiac preload and afterload and preventing hypertrophy and fibrosis in residual surviving myocardium with the use of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor antagonists. Thus clinical research has focused on strategies for an optimal reperfusion therapy during the first hours of developing myocardial infarction or long-term prevention of remodeling. However, despite standard therapy, prognosis remains serious in patients with large infarctions and severe left ventricular dysfunction (20). This may be due to the fact that the “first hours” have mostly elapsed before patients receive reperfusion therapy, and a large myocardial defect or cardiac aneurysm (Fig. 1) may not respond well to therapy.

Infarct expansion occurs after the first hours of developing myocardial infarction and precedes remodeling, hypertrophy, and fibrosis of residual myocardium. In fact, it occurs predominantly during healing of the “cardiac wound” when the normal collagen structure has been destroyed and the scar is formed. If the infarct heals without expansion, the heart maintains its shape and prognosis is good. Infarct expansion has been studied in some detail, and mechanical determinants have been defined. Physical exercise begun early after a myocardial infarction has promoted left ventricular dilatation and thinning of the infarct in animal experiments (9). In contrast, mechanical unloading by nitroglycerin or captopril has prevented infarct expansion and thinning in dogs and humans, especially when combined with reperfusion (17, 18). Thus the infarct scar mostly has been considered from a biophysical point of view. However, the cellular, biochemical, and molecular character-