Role of the endocardial endothelium in the negative inotropic effects of thiopental

BACKGROUND: Myocardial function is regulated by endocardial endothelium (EE). Several studies have demonstrated the involvement of vascular endothelium in regulating the vasoactive effects of anesthetic agents. Because vascular endothelium and EE form a contiguous layer, it was postulated that EE might also be involved in regulating the inotropic effects of anesthetics. The effects of thiopental on isolated feline papillary muscle with and without EE were examined. METHODS: The study was performed on isolated cat papillary muscles (n = 48). The effects of increasing doses of thiopental (1.5, 3, 6, 9, 12, and 24 micrograms/ml) on isometric and isotonic muscle contraction parameters were evaluated in three protocols under different experimental conditions. In the first 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 selectively damaged by a 1-s immersion in 0.5% Triton X-100 (group B, n = 8). In the second protocol, cumulative concentration responses for thiopental were obtained in muscles with (group C, n = 8) and without (group D, n = 8) EE, pretreated with 10(-3) M of the blocking NG-nitro-L-arginine methyl ester (L-NAME). In the third protocol, the same cumulative concentration responses were obtained for thiopental in muscles with (group E, n = 8) and without (group F, n = 8) EE after pretreatment with 5 x 10(-4) 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 micrograms/ml) no longer altered myocardial function. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental and mimicked the response obtained after EE was removed. Pretreatment with L-arginine slightly accentuated the negative inotropic effects of low doses of thiopental. CONCLUSIONS: The negative inotropic actions of small doses of thiopental depend on the presence of an intact EE. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental, suggesting possible involvement of the nitric oxide pathwa