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Cellular basis of chronic ventricular remodeling after myocardial infarction in rats
G Olivetti1, J M Capasso, L G Meggs
1Department of Pathology, University of Parma, Italy.
Insights
Myocardial infarction triggers compensatory hypertrophy, but significant cell loss leads to ventricular dilation and elevated wall stress, progressing towards heart failure.
Area of Science:
- Cardiovascular Biology
- Cardiac Remodeling
- Heart Failure Pathophysiology
Background:
- Myocardial infarction (MI) induces compensatory hypertrophy in surviving cardiomyocytes.
- The capacity of this hypertrophic response to normalize ventricular hemodynamics and wall stress post-MI is not fully understood.
Purpose of the Study:
- To investigate whether the hypertrophic response of surviving myocardium after infarction normalizes ventricular hemodynamics and wall stress.
- To assess the impact of infarct size on myocyte hypertrophy and cardiac function.
Main Methods:
- Induction of myocardial infarction in rats via left coronary artery ligation.
- Assessment of myocyte hypertrophy, ventricular hemodynamics (left ventricular end-diastolic pressure, left ventricular dP/dt), and diastolic wall stress at one month post-MI.
- Quantification of infarct size, viable myocardium, chamber dimensions, and myocyte cellular changes.
Main Results:
- Small infarcts (38% LV free wall) induced significant myocyte hypertrophy but resulted in increased ventricular end-diastolic pressure, decreased dP/dt, and 2.4-fold higher diastolic wall stress.
- Large infarcts (60% LV mass loss) showed greater myocyte hypertrophy but a 10% deficit in viable myocardium, leading to markedly depressed ventricular performance and ninefold higher diastolic wall stress.
- Both infarct groups exhibited chamber dilation due to increased chamber volume and decreased myocardial mass/chamber volume ratio, driven by anatomical and cellular changes.
Conclusions:
- Decompensated eccentric ventricular hypertrophy develops chronically after infarction.
- Myocyte growth is insufficient to normalize wall stress when myocyte loss exceeds approximately 40% of the left ventricular free wall.
- Persistent elevated myocardial and cellular loads may drive disease progression towards end-stage congestive heart failure.
Abstract:
To determine whether the hypertrophic response of the surviving myocardium after infarction leads to normalization of ventricular hemodynamics and wall stress, the left coronary artery was ligated in rats. One month later, the rats were killed. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium bordering and remote from the scar was documented by increases in myocyte cell volume per nucleus of 43% and 25%, respectively. These cellular enlargements resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), myocyte hypertrophy was 81% and 32% in the regions adjacent to and distant from the scar, respectively. A 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased ninefold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Chamber dilation was the consequence of the combination of gross anatomic and cellular changes consisting, in the presence of small infarcts, of a 6% and a 19% increase in transverse midchamber diameter and in average myocyte length per nucleus, respectively. In the presence of large infarcts, transverse and longitudinal chamber diameters expanded by 27% and 11%, respectively, myocyte length per nucleus expanded by 26%, and the mural number of myocytes decreased by 10%. In conclusion, decompensated eccentric ventricular hypertrophy develops chronically after infarction, and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistance of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.