Are there ventricle-specific postnatal maturational differences in myocardial beta-adrenoceptors?
Newborn hearts have restricted functional reserve and variable responsiveness to inotropes that could be partly due to differences in myocardial beta-adrenoceptors (beta-AR). To clarify this issue, this study documented ventricle-specific changes in myocardial beta-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 beta-AR density (B(max), fmol/g) and dissociation constant (K(d), pmol/L) were determined by radioligand binding with I125 iodocyanopindolol. Overall, beta-AR B(max) in the LV significantly decreased with maturation. Interestingly, newborn animal hearts (LV and RV) subdivided into 2 groups: an adult-like low K(d) group with low B(max) and a fetal-like high K(d) group with high B(max), which were significantly different from one another. The high K(d) newborn group also had significantly higher K(d) and B(max) 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, beta-AR density decreased, whereas LV beta-AR binding affinity increased. Variable beta-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.
Wittnich
Carin
C
Department of Surgery, University of Toronto, 1 King's College Circle, Medical Science Building, Room 7256, Toronto, Ontario M5G 1A8, Canada. c.wittnich@utoronto.ca
Belanger
Michael P
MP
Bandali
Karim
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015536:Down-Regulation; D006321:Heart / Q000254:growth & development*; D006352:Heart Ventricles / Q000254:growth & development / Q000378:metabolism; D020120:Iodocyanopindolol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013552:Swine
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol