Left ventricular unloading with an assist device results in receptor relocalization as well as increased beta-adrenergic receptor numbers: are these changes indications for outcome?
BACKGROUND
The use of left ventricular (LV) assist devices (LVADs) can improve performance and recovery of failing human hearts.


OBJECTIVE
Following our alpha-adrenergic receptor work, we hypothesized that mechanical unloading in patients with low output syndrome and LV failure would yield similar results with beta-adrenergic receptors ((beta)AR), that being increased numbers and intra-myocytic relocalization.


METHODS
(beta)AR density and localization were investigated by fluorescence deconvolution microscopy and compared at LVAD insertion and removal in 13 heart failure patients, the patients therefore acting as their own control. (beta)AR densities and distribution were determined in snap frozen sections of human core biopsy left ventricular apical tissue. Samples were probed with tagged CGP 12177 for visualization of (beta)AR and challenged with cold agonists and antagonists. (beta)AR density was measured by two independent methods. Localization of receptors was examined in reconstructed, deconvoluted, stacked section images.


RESULTS
There was an increase in (beta)AR density following ventricular unloading in most of the patients, and also significant normalization in the location of the receptors in the myocardium comparing pre- and post-LVAD tissue.


CONCLUSIONS
These findings suggest that supporting an ailing heart via unloading initiates mechanisms and pathways responsible for myocardial recovery and repair. With appropriate pharmacological support, patients with LVAD might recover to the point where they no longer depend on eventual organ transplantation, and (beta)AR number, type, and distribution in pre-LVAD myocardial tissue, could predict outcome with regard to recovery, repair, and improvement in cardiac function.
Bick
Roger J
RJ
Department of Cardiovascular Anesthesiology, The Texas Heart Institute and St. Luke's Episcopal Hospital, Houston, TX, USA. Roger.J.Bick@uth.tmc.edu
Grigore
Alina M
AM
Poindexter
Brian J
BJ
Schnee
Pippa M
PM
Nussmeier
Nancy A
NA
Gregoric
Igor D
ID
Shah
Nyma A
NA
Myers
Timothy J
TJ
Buja
L Maximilian
LM
Frazier
O Howard
OH
D005260:Female; D006352:Heart Ventricles; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000628:therapy*
D011943:Receptors, Adrenergic, beta