Bettens K M, De Hert S G, Sys S U, Brutsaert D L
Department of Anesthesiology, University of Antwerp, Belgium.
Anesthesiology. 1996 Nov;85(5):1100-10. doi: 10.1097/00000542-199611000-00019.
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.
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.
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.
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 pathway.
心肌功能受心内膜内皮(EE)调节。多项研究已证实血管内皮参与调节麻醉药的血管活性作用。由于血管内皮与EE形成连续层,因此推测EE可能也参与调节麻醉药的变力作用。本研究检测了硫喷妥钠对有或无EE的离体猫乳头肌的影响。
本研究在离体猫乳头肌(n = 48)上进行。在不同实验条件下,通过三个实验方案评估递增剂量的硫喷妥钠(1.5、3、6、9、12和24微克/毫升)对等长和等张肌肉收缩参数的影响。在第一个实验方案中,研究硫喷妥钠对EE完整的肌肉(A组,n = 8)和EE通过在0.5% Triton X - 100中浸泡1秒而被选择性损伤的肌肉(B组,n = 8)的影响。在第二个实验方案中,在预先用10⁻³ M的一氧化氮合酶抑制剂NG - 硝基 - L - 精氨酸甲酯(L - NAME)处理的有EE(C组,n = 8)和无EE(D组,n = 8)的肌肉中获得硫喷妥钠的累积浓度反应。在第三个实验方案中,在预先用5×10⁻⁴ M L - 精氨酸处理的有EE(E组,n = 8)和无EE(F组,n = 8)的肌肉中获得硫喷妥钠的相同累积浓度反应。
在EE完整的情况下,硫喷妥钠引起心肌功能呈剂量依赖性降低。去除EE后,低剂量的硫喷妥钠(1.5至6微克/毫升)不再改变心肌功能。用L - NAME预处理肌肉可抑制低剂量硫喷妥钠的负性变力作用,并模拟去除EE后获得的反应。用L - 精氨酸预处理可轻微增强低剂量硫喷妥钠的负性变力作用。
小剂量硫喷妥钠的负性变力作用取决于EE的完整性。用L - NAME预处理肌肉可抑制低剂量硫喷妥钠的负性变力作用,提示一氧化氮途径可能参与其中。