硫喷妥钠对离体雪貂心室肌负性肌力作用的机制。

Housmans P R, Kudsioglu S T, Bingham J

Mayo Medical School, Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.

Anesthesiology. 1995 Feb;82(2):436-50. doi: 10.1097/00000542-199502000-00014.

BACKGROUND

Thiopental's myocardial depressant effects are well known and most likely involve some alteration in intracellular Ca2+ homeostasis. The aim of this study was to investigate the mechanisms of thiopental's negative inotropic effects and its underlying mechanism in isolated ferret ventricular myocardium (which shows physiologic characteristics similar to human ventricular myocardium), and in frog ventricular myocardium, in which Ca2+ ions for myofibrillar activation are derived almost entirely from transsarcolemmal influx.

METHODS

The authors analyzed the effects of thiopental after beta-adrenoceptor blockade on variables of contractility and relaxation, and on the free intracellular Ca2+ transient detected with the Ca(2+)-regulated photoprotein aequorin. Thiopental's effects also were evaluated in ferret right ventricular papillary muscles in which the sarcoplasmic reticulum (SR) function was impaired by ryanodine and in frog ventricular strips with little or no SR function.

RESULTS

At concentration > or = 10(-4) M, which is in the high range of the clinically encountered free plasma thiopental concentrations, thiopental decreased contractility and the amplitude of the intracellular Ca2+ transient. At equal peak force, peak aequorin luminescence in 10(-4) M thiopental and [Ca2+]0 > 2.25 mM was slightly smaller than that in control conditions at [Ca2+]o = 2.25 mM. This indicates that thiopental causes a small increase in myofibrillar Ca2+ sensitivity. After inactivation of sarcoplasmic reticulum Ca2+ release with 10(-6) M ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca2+ influx, thiopental caused a further decrease in contractility and in the amplitude of the intracellular Ca2+ transient, and thiopental's relative negative inotropic effect was not different from that in control muscles not exposed to ryanodine. Thiopental, > or = 10(-4) M, decreased contractility in frog ventricular myocardium.

CONCLUSIONS

These findings indicate that the direct negative inotropic effect of thiopental results from a decrease in intracellular Ca2+ availability. At least part of thiopental's action is caused by inhibition of transsarcolemmal Ca2+ influx. These effects become apparent at concentrations routinely present during intravenous induction with thiopental.

背景

硫喷妥钠的心肌抑制作用众所周知，很可能涉及细胞内钙离子稳态的某些改变。本研究的目的是在离体雪貂心室肌（其生理特性与人类心室肌相似）以及蛙心室肌（其中肌原纤维激活所需的钙离子几乎完全来自跨肌膜内流）中研究硫喷妥钠负性肌力作用的机制及其潜在机制。

方法

作者分析了β肾上腺素能受体阻断后硫喷妥钠对收缩性和舒张变量以及用钙离子调节的光蛋白水母发光蛋白检测到的细胞内游离钙离子瞬变的影响。还在雪貂右心室乳头肌（其中肌浆网功能被兰尼碱损害）和肌浆网功能很少或没有的蛙心室条带中评估了硫喷妥钠的作用。

结果

在浓度≥10⁻⁴M时（该浓度处于临床所遇游离血浆硫喷妥钠浓度的高范围内），硫喷妥钠降低了收缩性和细胞内钙离子瞬变的幅度。在同等峰值力下，10⁻⁴M硫喷妥钠和[Ca²⁺]₀＞2.25mM时的峰值水母发光蛋白发光略小于[Ca²⁺]₀ = 2.25mM时对照条件下的发光。这表明硫喷妥钠使肌原纤维对钙离子的敏感性略有增加。在用10⁻⁶M兰尼碱使肌浆网钙离子释放失活后（在这种情况下肌原纤维激活几乎完全依赖于跨肌膜钙离子内流），硫喷妥钠导致收缩性和细胞内钙离子瞬变幅度进一步降低，且硫喷妥钠的相对负性肌力作用与未暴露于兰尼碱的对照肌肉中的作用无差异。≥10⁻⁴M的硫喷妥钠降低了蛙心室肌的收缩性。