Thiopentone inhibits beta-adrenergic responses in myocardial tissue.
The purpose of this study was to determine the importance of inhibition of beta-adrenergic function in thiopentone-induced myocardial depression. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to thiopentone (200 microM, 400 microM, 600 microM, 800 microM) were shifted to the right in preparations treated with 10(-3)M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10(-6) M dibutyryl cyclic isoprenaline, demonstrating that inhibition of beta-adrenergic mechanisms by thiopentone is physiologically important. Depression by thiopentone was similar in atria treated with 10(-5) M forskolin compared with preparations stimulated with 10(-6) M isoprenaline, indicating that thiopentone does not block beta-adrenergic receptors. It is concluded that thiopentone depresses myocardial function by several mechanisms, one of which involves inhibition of the adenyl cyclase cascade. The adenyl cyclase enzyme is a likely site where thiopentone inhibits the system; however, other components of the cascade may also be involved.
Thurston
T A
TA
Department of Anesthesiology, University of Texas Medical Branch at Galveston 77555, USA.
Mathew
B P
BP
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013874:Thiopental / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists; D018686:Anesthetics, Intravenous; D013874:Thiopental