Langeron O, Coirault C, Fratea S, Orliaguet G, Coriat P, Riou B
Department of Anesthesiology and Critical Care, Groupe Hospitalier Pitié-Salpêtrière, Paris VI University, France.
Anesth Analg. 1999 Aug;89(2):466-71. doi: 10.1097/00000539-199908000-00041.
Dantrolene is used in patients with muscle spasticity and is the only known effective treatment for malignant hyperthermia. However, its effects on muscle relaxation and energetics are unknown and may have important consequences in diaphragmatic function. We studied the effects of dantrolene (10(-8) to 10(-4) M) on diaphragm muscle strips (n = 12) in the hamster in vitro (Krebs-Henseleit solution, 29 degrees C, 95% oxygen/5% carbon dioxide) in response to tetanic stimulation (50 Hz). We studied contraction and relaxation under isotonic and isometric conditions, as well as energetics. Data are mean +/- SD. Dantrolene induced a negative inotropic effect in the hamster diaphragm (active force at 10(-4) M: 34% +/- 7% of baseline; P < 0.05) but did not significantly modify the curvature of the force-velocity relationship. Dantrolene did not significantly modify isotonic relaxation. Dantrolene, up to 10(-5) M, did not significantly impair isometric relaxation. In conclusion, dantrolene induced a marked negative inotropic effect on diaphragm muscle without affecting myothermal efficiency and relaxation.
Dantrolene induced a significant and concentration-dependent negative inotropic effect on diaphragm muscle but did not modify isotonic relaxation, which suggests no alteration of the calcium reuptake by the sarcoplasmic reticulum; up to 10(-5) M dantrolene did not alter isometric relaxation, i.e., myofilament calcium sensitivity. Dantrolene did not modify the energetics of diaphragm muscle.
丹曲林用于治疗肌肉痉挛患者，是已知唯一对恶性高热有效的治疗药物。然而，其对肌肉松弛和能量代谢的影响尚不清楚，可能对膈肌功能产生重要影响。我们研究了丹曲林（10⁻⁸至10⁻⁴M）对体外培养的仓鼠膈肌条（n = 12）（置于Krebs-Henseleit溶液中，29℃，95%氧气/5%二氧化碳）在强直刺激（50Hz）下的影响。我们研究了等张和等长条件下的收缩与松弛以及能量代谢。数据为平均值±标准差。丹曲林对仓鼠膈肌产生负性肌力作用（10⁻⁴M时的主动力：为基线的34%±7%；P < 0.05），但未显著改变力-速度关系的曲线。丹曲林未显著改变等张松弛。高达10⁻⁵M的丹曲林未显著损害等长松弛。总之，丹曲林对膈肌产生显著的负性肌力作用，但不影响肌热效率和松弛。
丹曲林对膈肌产生显著的、浓度依赖性的负性肌力作用，但未改变等张松弛，这表明肌浆网对钙的再摄取未改变；高达10⁻⁵M的丹曲林未改变等长松弛，即肌丝对钙的敏感性。丹曲林未改变膈肌的能量代谢。
