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The Pathophysiology of Myocardial Infarction: From Coronary Occlusion to Clinical Consequence

1Coronary Supply and the Myocardial Oxygen Balance2Atherosclerotic Plaque Rupture and Coronary Thrombosis3Ischemia: Metabolic and Functional Consequences of Oxygen Deprivation4From Reversible Injury to Irreversible Cell Death5Inflammation, Healing, and Infarct Remodeling6Clinical Manifestations: ECG, Biomarkers, and Pump Dysfunction
Inflammation, Healing, and Infarct Remodeling

Remodeling: Wall Thinning and Loss of Pump Function

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Start at the top with the left ventricular cross-section. The pale, thin segment is the infarct scar — it has no sarcomeres, so it cannot contract; it stays still or bulges outward during systole while the rest of the wall squeezes. The surviving myocardium must therefore eject the same stroke volume with less working tissue. Two compensations appear: the Frank–Starling mechanism, where a larger end-diastolic volume stretches the surviving myocytes and strengthens their contraction, and neurohormonal activation through sympathetic drive and the renin–angiotensin–aldosterone system, which raises contractility and holds blood pressure. Now follow the self-reinforcing cycle below. Rising wall stress drives hypertrophy and fibrosis, the chamber dilates, and because the scar is thin the dilation is asymmetric — the scar thins further and the chamber rounds out. The Laplace relationship, sigma equals pressure times radius divided by two times wall thickness, explains why: as radius rises and wall thickness falls, wall stress climbs for the same pressure, driving still more dilation and thinning. The endpoint is a larger, more spherical, less efficient ventricle — ejection fraction falls, filling pressures rise, and heart failure develops. How far this goes depends on infarct size, infarct location, and whether early reperfusion salvaged the border zone.
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A scar cannot generate force, so the infarcted segment becomes akinetic or dyskinetic — it either does not move or bulges outward during systole. The remaining viable myocardium must therefore produce the same stroke volume from less muscle. It compensates in two ways: acutely through the Frank–Starling mechanism, where increased end-diastolic volume stretches the surviving myocytes and increases their force of contraction, and chronically through neurohormonal activation — sympathetic drive and the renin–angiotensin–aldosterone system — which raises contractility and preserves blood pressure.

These compensations are effective in the short term but become maladaptive. Increased wall stress in the border zone and the surviving ventricle stimulates hypertrophy and interstitial fibrosis. The ventricle dilates, and because the infarcted region is thin and non-contractile, the dilation is asymmetric: the scar thins further and the chamber becomes more spherical. This is adverse remodeling. The Laplace relationship, \(\sigma = \frac{P \cdot r}{2h}\), explains why it is self-reinforcing: as the chamber radius \(r\) increases and the wall thickness \(h\) decreases, wall stress \(\sigma\) rises for the same pressure \(P\), which drives further dilation and further thinning.

The functional endpoint is a ventricle that is larger, more spherical, and less efficient. Ejection fraction falls, filling pressures rise, and the patient develops heart failure. The extent of remodeling depends on infarct size, infarct location, and whether reperfusion was achieved early enough to salvage myocardium at the border zone.

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