Mio Yasushi, Fukuda Norio, Kusakari Yoichiro, Amaki Yoshikiyo, Tanifuji Yasumasa, Kurihara Satoshi
Department of Anesthesiology, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan.
Anesthesiology. 2004 Oct;101(4):888-94. doi: 10.1097/00000542-200410000-00013.
Recent evidence suggests that ropivacaine exerts markedly less cardiotoxicity compared with bupivacaine; however, the mechanisms are not fully understood at the molecular level.
Isolated ferret ventricular papillary muscles were microinjected with the Ca-binding photoprotein aequorin, and intracellular Ca transients and tension were simultaneously measured during twitch in the absence and presence of bupivacaine or ropivacaine.
Bupivacaine and ropivacaine (10, 30, and 100 microm) reduced peak systolic [Ca]i and tension in a concentration-dependent manner. The effects were significantly greater for bupivacaine, particularly on tension (approximately twofold). The percentage reduction of tension was linearly correlated with that of [Ca]i for both anesthetics, with the slope of the relationship being approximately equal to 1.0 for ropivacaine and approximately equal to 1.3 for bupivacaine (slope difference, P < 0.05), suggesting that the cardiodepressant effect of ropivacaine results predominantly from inhibition of Ca transients, whereas bupivacaine suppresses Ca transients and the reaction beyond Ca transients, i.e., myofibrillar activation, as well. BAY K 8644, a Ca channel opener, abolished the inhibitory effects of ropivacaine on Ca transients and tension, whereas BAY K 8644 only partially inhibited the effects of bupivacaine, particularly the effects on tension.
The cardiodepressant effect of bupivacaine is approximately twofold greater than that of ropivacaine. Bupivacaine suppresses Ca transients more markedly than does ropivacaine and reduces myofibrillar activation, which may at least in part underlie the greater inhibitory effect of bupivacaine on cardiac contractions. These results suggest that ropivacaine has a more favorable profile as a local anesthetic in the clinical settings.
最近的证据表明,与布比卡因相比,罗哌卡因的心脏毒性明显较小;然而,其分子机制尚未完全明确。
将分离的雪貂心室乳头肌微量注射钙结合光蛋白水母发光蛋白,在不存在和存在布比卡因或罗哌卡因的情况下,同步测量抽搐期间的细胞内钙瞬变和张力。
布比卡因和罗哌卡因(10、30和100微摩尔)以浓度依赖性方式降低收缩期峰值[Ca]i和张力。布比卡因的作用明显更大,尤其是对张力的影响(约两倍)。两种麻醉剂的张力降低百分比与[Ca]i的降低百分比呈线性相关,罗哌卡因的关系斜率约等于1.0,布比卡因约等于1.3(斜率差异,P<0.05),这表明罗哌卡因的心脏抑制作用主要源于对钙瞬变的抑制,而布比卡因不仅抑制钙瞬变,还抑制钙瞬变之后的反应,即肌原纤维激活。钙通道开放剂BAY K 8644消除了罗哌卡因对钙瞬变和张力的抑制作用,而BAY K 8644仅部分抑制了布比卡因的作用,尤其是对张力的影响。
布比卡因的心脏抑制作用比罗哌卡因大约大两倍。布比卡因比罗哌卡因更明显地抑制钙瞬变并降低肌原纤维激活,这可能至少部分是布比卡因对心脏收缩具有更大抑制作用的基础。这些结果表明,罗哌卡因在临床环境中作为局部麻醉剂具有更有利的特性。