ROLE OF THE ENDOCARDIAL ENDOTHELIUM IN THE NEGATIVE INOTROPIC EFFECTSOF THIOPENTAL

Background: Myocardial function is regulated by endocardial endotheliu m (EE). Several studies have demonstrated the involvement of vascular endothelium in regulating the vasoactive effects of anesthetic agents. Because vascular endothelium and ER form a contiguous layer, it was p ostulated that EE might also be involved in regulating the inotropic e ffects of anesthetics. The effects of thiopental on isolated feline pa pillary muscle with and without EE were examined. Methods: The study w as performed on isolated cat papillary muscles (n = 48). The effects o f increasing doses of thiopental (1.5, 3, 6, 3, 12, and 24 mu g/ml) on isometric and isotonic muscle contraction parameters were evaluated i n three protocols under different experimental conditions. In the firs t protocol, the effects of thiopental were studied in the muscles with an intact EE (group A, n = 8) and muscles in which the EE was selecti vely damaged by a 1-s immersion in 0.5% Triton X-100 (group B, n = 8). In the second protocol, cumulative concentration responses for thiope ntal were obtained in muscles with (group C, n = 8) and without (group D, n = 8) EE, pretreated with 10(-3) M of the blocking, N-G-nitro-L-a rginine methly ester (L-NAME), In the third protocol, the same cumulat ive concentration responses were obtained for thiopental in muscles wi th (group B n = 8) and without (group F, n = 8) EE after pretreatment with 5 x 10(-2) M L-arginine. Results: In the presence of an intact EE , thiopental induced a dose-dependent decrease in myocardial function. With the EE removed, low doses of thiopental (1.5 to 6 mu g/ml) no lo nger altered myocardial function. Pretreatment of the muscles with L-N AME inhibited the negative inotropic effects of low doses of thiopenta l and mimicked the response obtained after EE was removed. Pretreatmen t with L-arginine slightly accentuated the negative inotropic effects of low doses of thiopental. Conclusions: The negative inotropic action s of small doses of thiopental depend on the presence of an intact EE. Pretreatment of the muscles with L-NAME inhibited the negative inotro pic effects of low doses of thiopental, suggesting possible involvemen t of the nitric oxide pathway.