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[4-氯-3-乙基苯酚能否用于恶性高热的症状前体外诊断?一项使用猪骨骼制剂的研究]

[Is a presymptomatic malignant hyperthermia in-vitro diagnosis with 4-chloro-3-ethyl phenol possible? A study using porcine skeletal preparations].

作者信息

Gerbershagen M U, Wappler F, Fiege M, Weisshorn R, Kolodzie K, Schulte am Esch J

机构信息

Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Hamburg-Eppendorf.

出版信息

Anasthesiol Intensivmed Notfallmed Schmerzther. 2004 Feb;39(2):81-6. doi: 10.1055/s-2004-817676.

Abstract

OBJECTIVE

The diagnosis of malignant hyperthermia is currently performed with the in-vitro contracture test (IVCT) with halothane and caffeine. This test has a sensitivity of 99.0 % but only a specificity of 93.6 %. A cumulative IVCT with 4-chloro-3-ethyl-phenole (CEP) has recently been shown to differentiate between MH susceptible (MHS) and MH normal (MHN) swine. The pur-pose of this study was to investigate the ability of bolus CEP-applications to distinguish between porcine MHS- and MHN-muscle specimens using the IVCT.

METHODS

After approval by the local animal care committee 8 MHS- and 8 MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administration of CEP in concentrations of 75 resp. 100 micro mol l (-1). Predefined parameters were: (1) onset time of the contracture development, (2) time to the achievement of the 2, 5 and 10 mN contracture level and (3) maximum contracture level. Data are expressed as medians and ranges.

RESULTS

After 75 micro mol l (-1) CEP administration all MHS-muscles showed contractures after 0.5 min (0.2 min/0.9 min). The 2 mN contracture level was reached by all MHS-, the 5 mN level by four MHS- and the 10 mN level by one MHS-specimen. The maximum contracture was 5.3 mN (2.4 mN/12.9 mN). The onset time after 100 micro mol l (-1) CEP was registered as 0.3 min (0.1 min/0.7 min) in the MHS-preparations. Again, the 2 mN level was achieved by all MHS-specimens, the 5 mN level by 5 and the 10 mN level by one MHS-bundle. The maximum contracture was measured as 5.9 mN (2.8 mN/13.9 mN). In 7 MHN-specimens no contracture development was measured. After 75 micro mol l (-1) CEP one MHN-muscle showed a maximum contracture of 1.0 mN, after 100 micro mol l (-1) CEP one MHN-bundle demonstrated a maximum contracture of 1.1 mN. Hence, a significant difference between MHS and MHN without overlap was revealed with both CEP-concentrations in the onset time of contracture, in the 2 mN contracture level and the maximum contracture.

CONCLUSION

Since a clear differentiation between MHS and MHN porcine specimens was achieved after bolus application of 75 and 100 micro mol l (-1) CEP, MH-diagnosis might be possible with a CEP-IVCT. It seems worthwhile to examine this hypothesis in men.

摘要

目的

目前恶性高热的诊断是通过使用氟烷和咖啡因的体外挛缩试验(IVCT)进行的。该试验的敏感性为99.0%,但特异性仅为93.6%。最近有研究表明,使用4-氯-3-乙基苯酚(CEP)进行累积IVCT可区分恶性高热易感(MHS)和恶性高热正常(MHN)猪。本研究的目的是探讨使用IVCT通过大剂量应用CEP区分猪MHS和MHN肌肉标本的能力。

方法

经当地动物护理委员会批准,对8头MHS猪和8头MHN猪进行麻醉并采集肌肉活检样本。对于IVCT,将肌肉标本暴露于浓度为75 μmol/L和100 μmol/L的大剂量CEP中。预定义参数为:(1)挛缩发展的起始时间,(2)达到2 mN、5 mN和10 mN挛缩水平的时间,以及(3)最大挛缩水平。数据以中位数和范围表示。

结果

给予75 μmol/L CEP后,所有MHS肌肉在0.5分钟(0.2分钟/0.9分钟)后出现挛缩。所有MHS标本均达到2 mN挛缩水平,4个MHS标本达到5 mN水平,1个MHS标本达到10 mN水平。最大挛缩为5.3 mN(2.4 mN/12.9 mN)。在MHS制剂中,给予100 μmol/L CEP后的起始时间记录为0.3分钟(0.1分钟/0.7分钟)。同样,所有MHS标本均达到2 mN水平,5个达到5 mN水平,1个MHS束达到10 mN水平。最大挛缩测量为5.9 mN(2.8 mN/13.9 mN)。在7个MHN标本中未检测到挛缩发展。给予75 μmol/L CEP后,1个MHN肌肉的最大挛缩为1.0 mN,给予100 μmol/L CEP后,1个MHN束的最大挛缩为1.1 mN。因此,在挛缩起始时间、达到2 mN挛缩水平和最大挛缩方面,两种CEP浓度均显示MHS和MHN之间存在显著差异且无重叠。

结论

由于在大剂量应用75 μmol/L和100 μmol/L CEP后能明确区分猪MHS和MHN标本,因此使用CEP-IVCT进行恶性高热诊断可能是可行的。在人体中检验这一假设似乎是值得的。

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