Mechanical unloading with an LVAD significantly increased developed tension in response to beta-adrenergic stimulation (0.68 vs 0.38 g/mm2; P<0.01) and beta-adrenergic receptor density (P<0.05).
Observational
Does mechanical unloading with an LVAD improve beta-adrenergic responsiveness and receptor density in failing human hearts?
Mechanical unloading with an LVAD reverses beta-adrenergic receptor downregulation and restores inotropic responsiveness in failing human hearts, indicating functional impairment is reversible.
Absolute Event Rate: 0.68% vs 0.38%
p-value: p=<0.01
BACKGROUND: Mechanical unloading of the failing human heart with a left ventricular assist device (LVAD) results in clinically documented reversal of chamber dilation and improvement of cardiac function. We tested the hypothesis that LVAD support normalizes the ability of cardiac muscle to respond to sympathetic nervous system stimulation by reversing the downregulation of beta-adrenergic receptors. METHODS AND RESULTS: Human LV tissue was obtained from nonfailing hearts of unmatched organ donors and failing hearts at the time of transplantation, with or without LVAD. Baseline contractile parameters and inotropic response to a beta-adrenergic agonist were measured in isolated trabecular muscles. beta-Adrenergic receptor density was quantified by radioligand binding. Results showed a significant increase in the response to beta-adrenergic stimulation after LVAD (developed tension increased by 0.76+/-0.09 g/mm(2) in nonfailing, 0.38+/-0.07 in failing, and 0.68+/-0.10 in failing+LVAD; P<0.01), accompanied by an increased density of beta-adrenergic receptors (58.7+/-9.6 fmol/mg protein in nonfailing, 26.2+/-3.8 in failing, and 63.0+/-8.3 in failing+LVAD; P<0.05). These changes were unrelated to the duration of support. CONCLUSIONS: Data demonstrate that mechanically supporting the failing human heart with an LVAD can reverse the downregulation of beta-adrenergic receptors and restore the ability of cardiac muscle to respond to inotropic stimulation by the sympathetic nervous system. This indicates that functional impairment of cardiac muscle in human heart failure is reversible.
Ogletree-Hughes et al. (2001) conducted an observational in Heart failure. Left ventricular assist device (LVAD) vs. Failing hearts without LVAD and nonfailing hearts was evaluated on Inotropic response to a beta-adrenergic agonist (developed tension) (p=<0.01). Mechanical unloading with an LVAD significantly increased developed tension in response to beta-adrenergic stimulation (0.68 vs 0.38 g/mm2; P<0.01) and beta-adrenergic receptor density (P<0.05).