Abstract 16581: Dissociation Between S100A1 Protein Levels and Recovery of Muscle Function After LVAD
S100A1 is an important modulator of contractile reserve in the heart through its actions on intracellular calcium cycling and mitochondrial energy production. Studies in animal models and in human cardiac myocytes have shown that S100A1 is decreased in failing hearts, and that restoring S100A1 levels is associated with reversal of contractile dysfunction. We tested the hypothesis that mechanically unloading the failing human heart with a left ventricular assist device (LVAD) would produce recovery of S100A1, and that the reversal would be associated with recovery of muscle function. Our work has established that decreased S100A1 protein does not produce changes in baseline contraction of cardiac muscle removed from failing human hearts. Mouse studies have suggested that S100A1 may actually be more important in regulating cardiac muscle function when demands are increased, such as during β-adrenergic stimulation. We measured S100A1 in a population of non-failing human hearts from unmatched organ donors (NF; n=26), a group of explanted failing hearts from transplant recipients (F; n=26), and a group of hearts from transplant patients who had been supported by an LVAD as a bridge to transplant (F+LVAD; n=23). In the same hearts, we studied the contractile function of trabecular muscles and their response to a single dose of the β-adrenergic agonist, isoproterenol (ISO). As shown in the figure, S100A1 levels were significantly decreased in F vs NF hearts (p < .05), and failed to recover after LVAD support (p < .01). The inotropic response to a single dose of ISO was also diminished in muscles taken from the same F hearts (p < .001). However, the muscle contraction response recovered after LVAD support to levels between F and NF, but not significantly different from NF. These data show that S100A1, unlike other calcium cycling proteins, does not recover following LVAD support of the failing human heart, and also suggest dissociation between S100A1 levels and contractile reserve.
- Heart failure
- Assisted circulation
- Excitation-contraction coupling (ECC)
- Beta-adrenergic receptor agonists
- © 2012 by American Heart Association, Inc.