Summary
The term ventricular remodeling has been coined to describe the geometrical changes in size and shape of the left ventricle occurring after large myocardial infarcts.
We do not exactly know what initiates this process. Slipping of myofilaments following destruction of connective tissue – probably due to metalloproteinase activation – could be the initial event.
As a consequence, wall stress is increased triggering deleterious adaptation processes, such as
– intracardiac angiotensin II generation
– cardiac endothelin formation and release
– pro-apoptotic signals for cardiomyocytes
– hypertrophic signals for fibroblasts and cardiomyocytes
This cascade of events is not only observed in the process of remodeling following myocardial infarction but is also operating during the progression of heart failure.
Therapeutic principles therefore are similar in both conditions:
– reduction of wall stress (pharmacological or mechanical unloading of the heart)
– blockade of angiotensin II generation or of AT1-receptors (ACEinhibitors or AT1 antagonists)
– blockade of endothelin receptors (ETA-blockers)
– blockade of adrenergic receptors (preferably β1-adrenergic receptor blockers).
Better understanding of the molecular mechanisms of the remodeling process already has fueled the search for new therapeutic interventions (such as endothelin receptor blockers, aldosterone antagonists and growth hormone application). Continuous research in this field may be especially rewarding if we will succeed in identifying the very first step in the cascade.
Key words
Wall stress - angiotensin - endothelin - apoptosis
