通过体外咖啡因-氟烷挛缩试验（CHCT）进行诊断的多数恶性高热易感患者对氟烷出现过度的肌肉收缩反应，但对咖啡因无反应（氟烷过敏）。氟烷过敏的患者常常在静息时出现肌肉和骨骼方面的症状，并出现肌肉中存在异常的钙事件。通过测量肌管束对氟烷的敏感度，并将临床观察和细胞水平的研究扩展到大量的患者群体，我们对恶性高热易感的病理机制有了新的认识。恶性高热易感患者被分为HH和HS亚组（仅对氟烷呈阳性和对咖啡因和氟烷均呈阳性）。在肌管束中测量氟烷浓度在0.5%至3%之间的浓度对[Ca2+] 进行的影响比较CHCT对肌肉的反应。对于67个患者，确定了概括其症状的临床指数，以及概括其原发肌肉细胞中静息[Ca2+]和自发和电刺激引发的Ca2+事件的钙指数。氟烷过敏的肌管束对0.5％的氟烷的反应比咖啡因-氟烷过敏的肌管束更高（P <0.001），但对于较高的浓度（与CHCT使用的浓度相当）的反应却较低（P = 0.055）。HH组钙指数更高（P <0.001），但其临床指数与HS相比并未显著升高。主成分分析确定了电刺激引发的Ca2+尖峰和静息[Ca2+]作为亚组分离的最强变量。增强的去极化和对氟烷的敏感性似乎是恶性高热易感的氟烷过敏患者的主要、互相加强的表型定义缺陷。版权所有©2023年英国麻醉学杂志。由Elsevier Ltd出版。保留所有权利。

Most patients with malignant hyperthermia susceptibility diagnosed by the in vitro caffeine-halothane contracture test (CHCT) develop excessive force in response to halothane but not caffeine (halothane-hypersensitive). Hallmarks of halothane-hypersensitive patients include high incidence of musculoskeletal symptoms at rest and abnormal calcium events in muscle. By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, we reach new insights into the pathological mechanism of malignant hyperthermia susceptibility.Patients with malignant hyperthermia susceptibility were classified into subgroups HH and HS (positive to halothane only and positive to both caffeine and halothane). The effects on [Ca2+]cyto of halothane concentrations between 0.5 and 3 % were measured in myotubes and compared with CHCT responses of muscle. A clinical index that summarises patient symptoms was determined for 67 patients, together with a calcium index summarising resting [Ca2+]cyto and spontaneous and electrically evoked Ca2+ events in their primary myotubes.Halothane-hypersensitive myotubes showed a higher response to halothane 0.5% than the caffeine-halothane hypersensitive myotubes (P<0.001), but a lower response to higher concentrations, comparable with that used in the CHCT (P=0.055). The HH group had a higher calcium index (P<0.001), but their clinical index was not significantly elevated vs the HS. Principal component analysis identified electrically evoked Ca2+ spikes and resting [Ca2+]cyto as the strongest variables for separation of subgroups.Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.