Are there ventricle-specific postnatal maturational differences in myocardial β-adrenoceptors?

Abstract

Newborn hearts have restricted functional reserve and variable responsiveness to inotropes that could be partly due to differences in myocardial β-adrenoceptors (β-AR). To clarify this issue, this study documented ventricle-specific changes in myocardial β-AR density and affinity during postnatal maturation. In vivo left and right ventricle (LV and RV, respectively) biopsies were obtained from newborn (3-day-old, n = 11), immature (14-day-old, n = 7), and adult (n = 6) pigs. Total β-AR density (Bmax, fmol/g) and dissociation constant (Kd, pmol/L) were determined by radioligand binding with I125 iodocyanopindolol. Overall, β-AR Bmax in the LV significantly decreased with maturation. Interestingly, newborn animal hearts (LV and RV) subdivided into 2 groups: an adult-like low Kd group with low Bmax and a fetal-like high Kd group with high Bmax, which were significantly different from one another. The high Kd newborn group also had significantly higher Kd and Bmax than both immature and adult hearts. Newborns had similar Bmax but higher Kd in the LV than the RV, whereas immature and adult hearts did not have ventricular differences. During maturation, β-AR density decreased, whereas LV β-AR binding affinity increased. Variable β-AR maturity was also identified immediately post partum, which could potentially explain the newborn heart’s variable responsiveness to inotropes. The subset of newborn hearts with lower binding affinity (reduced responsiveness) could also contribute to the newborn heart’s overall reduction in functional reserve.