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[4-chloro-m-cresol-induced contractures of skeletal muscle specimen from patients at risk for malignant hyperthermia].

Abstract

PURPOSE

4-chloro-m-cresol (4-CmC), commonly used as preservative, has been shown to induce contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MH). It has been suggested that a defect of the calcium release channel of the skeletal muscle sarcoplasmic reticulum (ryanodine receptor) in MH susceptible (MHS) patients could be responsible for this phenomenon. 4-CmC was found to be a potent activator of ryanodine receptor-mediated Ca2+ release. The aim of this study was to determine the in vitro effects of 4-CmC on muscle specimens from MHS and normal (MHN) patients, and whether contracture testing with different concentrations of 4-CmC could result in a more precise discrimination between MHS and MHN.

METHODS

In this prospective study muscle biopsies were obtained from 40 patients with clinical suspicion of MH. The patients were first classified by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the 4-CmC study.

RESULTS

Cumulative administration of 4-CmC (25, 50, 75, 100, 150, and 200 mumol/l) produced contractures in a concentration-dependent manner. However, contractures developed significantly earlier and were greater in MHS (n = 17) than in MHN specimens (n = 23). After bolus administration of 50, 75, and 100 mumol/l 14-CmC MHS specimens developed distinct muscle contractures. In contrast, in MHN specimens only 100 mumol/l 4-CmC produced contractures. All contracture levels following bolus administration of 100 mumol/l 4-CmC were attained significantly earlier in MHS than in MHN. There was no overlapping in the range of times between both groups.

CONCLUSION

In vitro contracture testing with 4-CmC seems to be a specific method to distinguish between MHS and MHN patients. However, the question whether 4-CmC is an MH-triggering agent is not completely solved. 4-CmC is a preservative within a large number of commercially available preparations (e.g. insulin, hormones, etc.). Regarding the results of contracture testing with 4-CmC it has been suggested that 4-CmC possibly represents a high-risk agent for MHS individuals. To reduce the risk of MH in susceptible patients due to administration of chlorocresols, we recommend avoiding preparations containing the preservative 4-CmC.

Authors+Show Affiliations

Abteilung für Anästhesiologie, Universitäts-Krankenhaus Eppendorf, Hamburg.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article

Language

ger

PubMed ID

9417254

Citation

Wappler, F, et al. "[4-chloro-m-cresol-induced Contractures of Skeletal Muscle Specimen From Patients at Risk for Malignant Hyperthermia]." Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS, vol. 32, no. 9, 1997, pp. 541-8.
Wappler F, Scholz J, von Richthofen V, et al. [4-chloro-m-cresol-induced contractures of skeletal muscle specimen from patients at risk for malignant hyperthermia]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1997;32(9):541-8.
Wappler, F., Scholz, J., von Richthofen, V., Fiege, M., Steinfath, M., & Schulte am Esch, J. (1997). [4-chloro-m-cresol-induced contractures of skeletal muscle specimen from patients at risk for malignant hyperthermia]. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS, 32(9), 541-8.
Wappler F, et al. [4-chloro-m-cresol-induced Contractures of Skeletal Muscle Specimen From Patients at Risk for Malignant Hyperthermia]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1997;32(9):541-8. PubMed PMID: 9417254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [4-chloro-m-cresol-induced contractures of skeletal muscle specimen from patients at risk for malignant hyperthermia]. AU - Wappler,F, AU - Scholz,J, AU - von Richthofen,V, AU - Fiege,M, AU - Steinfath,M, AU - Schulte am Esch,J, PY - 1998/1/7/pubmed PY - 1998/1/7/medline PY - 1998/1/7/entrez SP - 541 EP - 8 JF - Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS JO - Anasthesiol Intensivmed Notfallmed Schmerzther VL - 32 IS - 9 N2 - PURPOSE: 4-chloro-m-cresol (4-CmC), commonly used as preservative, has been shown to induce contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MH). It has been suggested that a defect of the calcium release channel of the skeletal muscle sarcoplasmic reticulum (ryanodine receptor) in MH susceptible (MHS) patients could be responsible for this phenomenon. 4-CmC was found to be a potent activator of ryanodine receptor-mediated Ca2+ release. The aim of this study was to determine the in vitro effects of 4-CmC on muscle specimens from MHS and normal (MHN) patients, and whether contracture testing with different concentrations of 4-CmC could result in a more precise discrimination between MHS and MHN. METHODS: In this prospective study muscle biopsies were obtained from 40 patients with clinical suspicion of MH. The patients were first classified by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the 4-CmC study. RESULTS: Cumulative administration of 4-CmC (25, 50, 75, 100, 150, and 200 mumol/l) produced contractures in a concentration-dependent manner. However, contractures developed significantly earlier and were greater in MHS (n = 17) than in MHN specimens (n = 23). After bolus administration of 50, 75, and 100 mumol/l 14-CmC MHS specimens developed distinct muscle contractures. In contrast, in MHN specimens only 100 mumol/l 4-CmC produced contractures. All contracture levels following bolus administration of 100 mumol/l 4-CmC were attained significantly earlier in MHS than in MHN. There was no overlapping in the range of times between both groups. CONCLUSION: In vitro contracture testing with 4-CmC seems to be a specific method to distinguish between MHS and MHN patients. However, the question whether 4-CmC is an MH-triggering agent is not completely solved. 4-CmC is a preservative within a large number of commercially available preparations (e.g. insulin, hormones, etc.). Regarding the results of contracture testing with 4-CmC it has been suggested that 4-CmC possibly represents a high-risk agent for MHS individuals. To reduce the risk of MH in susceptible patients due to administration of chlorocresols, we recommend avoiding preparations containing the preservative 4-CmC. SN - 0939-2661 UR - https://www.unboundmedicine.com/medline/citation/9417254/[4_chloro_m_cresol_induced_contractures_of_skeletal_muscle_specimen_from_patients_at_risk_for_malignant_hyperthermia]_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-995108 DB - PRIME DP - Unbound Medicine ER -