Endogenous norepinephrine stimulates both alpha 1- and beta-adrenoceptors in myocardium from children with congenital heart defects.
Atrial tissue removed from the cannulation site prior to cardioplegia (n = 15), and ventricular tissue therapeutically excised from the outflow tract of the right ventricle, (RVOT) (n = 2) were examined with respect to adrenoceptor mediated inotropic effect in children with congenital heart defects (CHD). We used sequential reversal by adrenoceptor antagonists of the tyramine enhanced response to endogenous norepinephrine to quantify the role of the beta- and the alpha 1-adrenoceptors, respectively, in the intropic response. Atrial myocardium had an alpha 1-adrenoceptor mediated component of 14% (median) (range 0-44%) and a beta-adrenoceptor mediated component of 86% (median) (range 56-100%). The patients with the highest alpha 1-adrenoceptor mediated inotropic components, had right ventricular pressure loads in the systemic range. In one specimen from RVOT, the ventricular alpha 1-adrenoceptor component was estimated to be 22% of the total inotropic response, compared to 26% in the corresponding right atrium. In a ventricular specimen from another patient, we could not demonstrate any alpha 1-adrenoceptor mediated inotropic component in contrast to 13% in the right atrium. This patient, however, had infusion of the alpha-adrenoceptor antagonist phentolamine after the excision of atrial tissue, but before the excision of muscular tissue from RVOT. In myocardium of children with CHD we found evidence that endogenous norepinephrine stimulated alpha 1-adrenoceptors in addition to beta-adrenoceptors. The relative contributions from the two adrenoceptors to the inotropic response varied considerably, and may be related to the pressure load of the right ventricle. These observations may be relevant with respect both to pathophysiology and to choice of drug therapy.
Borthne
K
K
Department of Pharmacology, University of Oslo, Norway.
Hågå
P
P
Langslet
A
A
Lindberg
H
H
Skomedal
T
T
Osnes
J B
JB
D002648:Child; D002675:Child, Preschool; D005260:Female; D006325:Heart Atria; D006330:Heart Defects, Congenital / Q000378:metabolism / Q000503:physiopathology*; D006352:Heart Ventricles; D006801:Humans; D007223:Infant; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013771:Tetralogy of Fallot / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology
D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin