Changing the remodeling process in heart failure: basic mechanisms and laboratory results.
Heart failure continues to be a major source of death and disability, and concepts and understanding of the disorder continue to evolve. There is now widespread recognition that myocardial remodeling is an important driving force behind the progression of heart failure. Both scientists and clinicians strive to understand the remodeling process better. Several animal models have been helpful in this regard. Yet controversy and uncertainties persist regarding the fundamental mechanisms of cardiac remodeling. To appreciate better the contribution of diminished contractility to the syndrome of heart failure, a number of laboratories have studied isolated cardiac myocyte function, both in animal models and in humans with cardiomyopathy. Results have been mixed and contradictory. A consistent theme found in many studies, however, is that the cells assume a more elongated shape. There may or may not be concurrent incremental changes in myocyte transverse diameter, depending on the model under study. At least two groups have claimed that maximal contractile properties of myocytes isolated from human failing hearts and from animals with experimental heart failure are normal, but this may depend on where the cells are taken in reference to acute myocardial injury. There are some important model-specific considerations when interpreting the results of isolated myocyte studies. Nevertheless, such experiments reinforce the concept that structural changes during cardiac remodeling, including myocyte growth, deposition of collagen, cell dropout, and perhaps myocyte slippage, all contribute to the architectural changes in the geometry of the left ventricle. The quantitative contribution that each structural change makes is not yet entirely clear. Studies in humans suggest that myocyte elongation may be the dominant mechanism, but it cannot account for the disproportionate increase in chamber size relative to myocyte length. Therefore, myocyte slippage is likely making some contribution to cardiac remodeling. Whether the remodeling process can be reversed is currently a topic of great research interest. Preliminary data from studies of left ventricular assist devices and beta-adrenergic blockers suggest that attenuation of progression and perhaps even reversal of remodeling is possible.
Francis
G S
GS
Cardiology Department, Cleveland Clinic Foundation, OH 44195, USA.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D048429:Cell Size / Q000502:physiology; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006353:Heart-Assist Devices; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D016277:Ventricular Function, Left / Q000502:physiology
D000319:Adrenergic beta-Antagonists