Location and density of alpha- and beta-adrenoreceptor sub-types in myocardium after mechanical left ventricular...

We hypothesized that not all subtypes of alpha- and beta-adrenoreceptors undergo similar upregulation and redistribution in human myocardium after mechanical unloading with an assist device.

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 alpha- and beta-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.

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 beta(2)- and alpha(1)-receptors and in alpha(1A) subtypes.

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.