Location and Density of α- and β-Adrenoreceptor Sub-types in Myocardium After Mechanical Left Ventricular Unloading
Received 10 April 2007; received in revised form 13 February 2008; accepted 27 March 2008. published online 21 May 2008.
Background
We hypothesized that not all subtypes of α- and β-adrenoreceptors undergo similar upregulation and redistribution in human myocardium after mechanical unloading with an assist device.
Methods
We obtained core biopsy samples of the left ventricle in 19 patients before and after removal of a Jarvik or Thoratec left ventricular assist device (LVAD) to study the effect of mechanical unloading on the distribution of α- and β-adrenoreceptors. Fresh, embedded tissue sections were incubated with receptor blockers and antibodies before the fluorescent labeling of receptors. Images were obtained by fluorescence deconvolution microscopy, and composite tissue renditions were made from the stacked images. Multiple adrenoreceptor subtypes were studied.
Results
We saw a reversal of myocyte hypertrophy in all patients, but the upregulation of receptors was not seen in all post-LVAD tissue samples. Furthermore, we noted receptor relocalization from an initial punctate/clumped pattern to a normal homogeneous distribution in many patients. Significant differences were seen in the distribution of β2- and α1-receptors and in α1A subtypes.
Conclusions
In this study we show not only the expected reversal of myocyte hypertrophy and the increase in adrenoreceptors after ventricular unloading, but also the relocalization of specific receptor subtypes.
aDepartment of Cardiovascular Surgical Research and Texas Heart Institute, St Luke's Episcopal Hospital, Houston, Texas
bDepartment of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, Texas
cDepartment of Cardiovascular Pathology, Texas Heart Institute, St Luke's Episcopal Hospital, Houston, Texas
dDepartment of Surgery, University of Texas Medical School at Houston, Houston, Texas.
Reprint requests: Roger J. Bick, FAHA, Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, MSB 2.288, 6431 Fannin Street, Houston, TX 77030. Telephone: 713-500-5406. Fax: 713-500-0730.
ABSTRACT