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 outf low tract of the right ventricle, (RVOT)(1) (n = 2) were examined with respect to adrenoceptor mediated inotropic effect in children with co ngenital heart defects (CHD). We used sequential reversal by adrenocep tor antagonists of the tyramine enhanced response to endogenous norepi nephrine to quantify the role of the beta- and the alpha(1)-adrenocept ors, 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 in otropic components, had right ventricular pressure loads in the system ic range. In one specimen from RVOT, the ventricular al-adrenoceptor c omponent was estimated to be 22% of the total inotropic response, comp ared to 26% in the corresponding right atrium, In a ventricular specim en from another patient, we could not demonstrate any alpha(1)-adrenoc eptor mediated inotropic component in contrast to 13% in the right atr ium, This patient, however, had infusion of the a-adrenoceptor antagon ist phentolamine after the excision of atrial tissue, but before the e xcision of muscular tissue from RVOT. In myocardium of children with C HD we found evidence that endogenous norepinephrine stimulated alpha(1 )-adrenoceptors in addition to beta-adrenoceptors, The relative contri butions from the two adrenoceptors to the inotropic response varied co nsiderably, and may be related to the pressure load of the right ventr icle. These observations may be relevant with respect both to pathophy siology and to choice of drug therapy.