Hartung E, Koob M, Anetseder M, Schoemig P, Krauspe R, Hogrefe G, Engelhardt W
Institute of Anaesthesiology, University of Wuerzburg, Germany.
Acta Anaesthesiol Scand. 1996 Apr;40(4):437-44. doi: 10.1111/j.1399-6576.1996.tb04466.x.
Recent studies demonstrated different contracture responses in muscle from malignant hyperthermia susceptible (MHS) compared to normal (MHN) individuals following exposure to the plant alkaloid ryanodine in-vitro. To confirm if ryanodine has a specific action in MHS muscle, the effect of a single concentration was investigated in skeletal muscle from MHS, MHN and control subjects using a new evaluation technique. In-vitro contracture test (IVCT) and MH diagnosis were performed according to the European Protocol in 86 patients sent to us for MH diagnostic testing and in 24 controls. Viable fresh muscle bundles were exposed to a single bolus of ryanodine 1.0 microM. Contracture onset time (OTp: defined as the time (min) from administration of ryanodine to the start of a contracture as measured by a contracture exceeding predrug baseline height), and the time to an increase of the baseline height to 10 mN above the predrug level (10Tp) were recorded. 29 patients were identified by IVCT to be MHS, 50 MHN, 7 MHE (equivocal) and 24 controls MHN. The indices from the ryanodine test separated all MHS (OTp: < 16 min; 10Tp < 27.4 min) from MHN (> 18 and > 27.7 min) and control subjects (> 17.4 and > 29 min). Values for MHE (equivocal) individuals ranged from 17.1 to 27.8 min for the OTp and from 32 to 49.2 min for the 10Tp. 5 patients with fulminant MH crises were included in the MHS group and showed the 95% confidence intervals (CI) of the median value < or = 8.05 min (OTp) and < or = 13.35 min (10TP) for MHS. In contrast, CI of the median value for the control group were found to be > or = 25.2 min (OTp) and 43.15 min (10Tp) for normal muscle. Thus the ryanodine test protocol showed markedly different contractures in MHS and MHN or control muscle. These results suggest that MHS muscle has a higher sensitivity to ryanodine. However, the protocol should be investigated for reproducibility and validation of thresholds by other laboratories. Ryanodine can help to improve MH diagnostic tests.
最近的研究表明，与正常个体（MHN）相比，恶性高热易感个体（MHS）的肌肉在体外暴露于植物生物碱ryanodine后会产生不同的挛缩反应。为了确定ryanodine在MHS肌肉中是否具有特定作用，使用一种新的评估技术，研究了单一浓度的ryanodine对MHS、MHN和对照受试者骨骼肌的影响。根据欧洲协议，对86名因MH诊断测试而被送到我们这里的患者和24名对照者进行了体外挛缩试验（IVCT）和MH诊断。将有活力的新鲜肌束暴露于1.0 microM的单次ryanodine推注中。记录挛缩起始时间（OTp：定义为从给予ryanodine到挛缩开始的时间（分钟），挛缩通过超过给药前基线高度来测量），以及基线高度增加到比给药前水平高10 mN的时间（10Tp）。通过IVCT鉴定出29例患者为MHS，50例为MHN，7例为MHE（可疑），24名对照者为MHN。ryanodine试验的指标将所有MHS（OTp：<16分钟；10Tp<27.4分钟）与MHN（>18分钟和>27.7分钟）及对照受试者（>17.4分钟和>29分钟）区分开来。MHE（可疑）个体的OTp值范围为17.1至27.8分钟，10Tp值范围为32至49.2分钟。5例暴发性MH危机患者被纳入MHS组，其MHS的中位数的95%置信区间（CI）<或=8.05分钟（OTp）和<或=13.35分钟（10TP）。相比之下，对照组正常肌肉中位数的CI被发现>或=25.2分钟（OTp）和43.15分钟（10Tp）。因此，ryanodine试验方案显示MHS与MHN或对照肌肉的挛缩明显不同。这些结果表明MHS肌肉对ryanodine具有更高的敏感性。然而，该方案应通过其他实验室进行重复性和阈值验证的研究。Ryanodine有助于改善MH诊断测试。
