Sato H
First Department of Anesthesiology, Toho University School of Medicine, Tokyo.
Masui. 1998 Nov;47(11):1296-301.
To determine whether ketamine has a possibility to predispose a patient to malignant hyperthermia (MH), the author investigated the effects of ketamine on the intracellular calcium kinetics with the skinned fiber technique in skeletal muscle cells of guinea pigs. Intracellular calcium kinetics including calcium induced calcium release (CICR) from sarcoplasmic reticulum (SR), calcium uptake into SR, and sensitivity of contractile proteins for calcium were assessed by using calcium concentration-response relationships. The effects of ketamine on the calcium concentration-response curves, which were constructed by changing calcium concentration from 10(-7) to 10(-4.5) M, were determined with ketamine concentrations of 0.1, 0.3, 1.0 and 3.0 mM. The author found that the rate of CICR was not altered with any ketamine concentration, while initial rate of calcium uptake into SR decreased and calcium rate (pCa)-tension curves shifted leftward with ketamine concentration of 3 mM at low concentrations of Ca2+ (below pCa 5.5). Thus, ketamine is not associated directly with occurrence of MH because ketamine has no significant effects on CICR. However, an increase in intracellular calcium concentration due to depressed calcium uptake into SR and an increased sensitivity of contractile proteins for calcium may lead to symptoms and signs like MH.
为了确定氯胺酮是否有可能使患者易患恶性高热(MH),作者采用皮肤纤维技术在豚鼠骨骼肌细胞中研究了氯胺酮对细胞内钙动力学的影响。通过使用钙浓度-反应关系评估细胞内钙动力学,包括肌浆网(SR)的钙诱导钙释放(CICR)、钙摄取到SR以及收缩蛋白对钙的敏感性。通过将钙浓度从10^(-7) 改变到10^(-4.5) M构建钙浓度-反应曲线,测定氯胺酮浓度为0.1、0.3、1.0和3.0 mM时氯胺酮对该曲线的影响。作者发现,任何氯胺酮浓度下CICR的速率均未改变,而在低钙浓度(低于pCa 5.5)时,当氯胺酮浓度为3 mM时,钙摄取到SR的初始速率降低,钙速率(pCa)-张力曲线向左移动。因此,氯胺酮与MH的发生没有直接关联,因为氯胺酮对CICR没有显著影响。然而,由于钙摄取到SR减少导致细胞内钙浓度增加以及收缩蛋白对钙的敏感性增加,可能会导致类似MH的症状和体征。