THIOPENTONE INHIBITS BETA-ADRENERGIC RESPONSES IN MYOCARDIAL TISSUE

The purpose of this study was to determine the importance of inhibitio n of beta-adrenergic function in thiopentone-induced myocardial depres sion. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to thiopentone (200 mu M, 400 mu M, 600 mu M 800 mu M) were shifted to the right in preparations treated w ith 10(-3) M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10(-6) M isoprenaline, demonstrating that i nhibition of beta-adrenergic mechanisms by thiopentone is physiologica lly 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-ad renergic receptors. It is concluded that thiopentone depresses myocard ial function by several mechanisms, one of which involves inhibition o f the adenyl cyclase cascade. The adenyl cyclase enzyme is a likely si te where thiopentone inhibits the system; however, other components of the cascade may also be involved.