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 regulation of the myocardial contractile force in children operated on for congenital heart defects (CHD). We measured the development of the isometric force of contraction dT/dtmax (T'max). Reduction in basal contractility induced by the beta-adrenoceptor antagonist timolol indicated that the myocardium was about half-maximally stimulated by endogenous norepinephrine (NE), probably released from nerve endings by the electrical stimulation. The inotropic effect of endogenous NE could be further increased by tyramine (EC50 approximately 5 microM). A maximal concentration of tyramine increased T'max by a median of 62.5% above the basal level. Sequential blockade of the beta- and alpha 1-adrenoceptors after tyramine stimulation by timolol and prazosin, respectively, 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 of endogenous NE may conceal inotropic effects by exogenous alpha-agonists added to this type of preparation. This preparation is suitable for studying adrenergic regulation by reversing the effects of endogenous NE.
Borthne
K
K
Department of Pharmacology, University of Oslo, Norway.
Hågå
P
P
Langslet
A
A
Lindberg
H
H
Osnes
J B
JB
Skomedal
T
T
D000293:Adolescent; D016275:Atrial Function; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006330:Heart Defects, Congenital / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012044:Regression Analysis; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013999:Timolol; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin