FUNCTIONAL-CHARACTERIZATION OF AN EX-VIVO PREPARATION OF ATRIAL MYOCARDIUM FROM CHILDREN WITH CONGENITAL HEART-DEFECTS - SENSITIVITY TO TYRAMINE AND ADRENOCEPTOR ANTAGONISTS

Small pieces of atrial tissue removed from the cannulation site before cardioplegia were used to develop a method for studying adrenergic re gulation of the myocardial contractile force in children operated on f or congenital heart defects (CHD). We measured the development of the isometric force of contraction dT/dt(max) (T'(max)). Reduction in basa l contractility induced by the beta-adrenoceptor antagonist timolol in dicated that the myocardium was about half-maximally stimulated by end ogenous norepinephrine (NE), probably released from nerve endings by t he electrical stimulation. The inotropic effect of endogenous NE could be further increased by tyramine (EC(50) similar to 5 mu M). A maxima l concentration of tyramine increased T'(max) by a median of 62.5% abo ve the basal level. Sequential blockade of the beta- and alpha(1)-adre noceptors after tyramine stimulation by timolol and prazosin, respecti vely, indicated that a near-maximal response to combined adrenoceptor stimulation by endogenous NE was mediated by both beta-adrenoceptors ( median 77%) and alpha(1)-adrenoceptors (median 23%). The basal level o f endogenous NE may conceal inotropic effects by exogenous alpha-agoni sts added to this type of preparation. This preparation is suitable fo r studying adrenergic regulation by reversing the effects of endogenou s NE.