[Effects of 4-hydroxybenzoic acid methyl ester on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pig].
The amide-linked local anesthetics can be used safely in patients susceptible to malignant hyperthermia (MH). 4-Hydroxybenzoic acid methyl ester contained as a preservative in local anesthetic solution was suspected to have triggered MH in a patient who had received nerve block with lidocaine solution. The author investigated the effects of 4-hydroxybenzoic acid methyl ester on Ca(2+)-related functions of the skeletal muscle using saponin-treated skinned fibers from the extensor digitorum longus muscle of guinea pigs. 4-Hydroxybenzoic acid methyl ester accelerated the Ca2+ induced Ca2+ release (CICR) rate from the sarcoplasmic reticulum (SR) in a dose-dependent manner, and the Ca2+ concentration-CICR rate curves were shifted to the left with 4-hydroxybenzoic acid methyl ester at concentrations above 30 microM. 30 microM of 4-hydroxybenzoic acid methyl ester is associated with a plasma concentration of lidocaine intoxication which induces general convulsion. Ca2+ uptake, initial rate of Ca2+ uptake by the SR and Ca2+ sensitivity of the contractile system were not affected by 100 microM of 4-hydroxybenzoic acid methyl ester. These results suggest that amide-type local anesthetic solutions and agents containing 4-hydroxybenzoic acid methyl ester as a preservative may trigger MH in MH susceptible patients, if they are accidentally administered into the blood vessel.
Nagasawa
M
M
First Department of Anesthesiology, Toho University School of Medicine, Tokyo.
D000779:Anesthetics, Local / Q000009:adverse effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008012:Lidocaine / Q000009:adverse effects; D008297:Male; D008305:Malignant Hyperthermia / Q000209:etiology; D018482:Muscle, Skeletal / Q000187:drug effects*; D010226:Parabens / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012996:Solutions
D000779:Anesthetics, Local; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D012996:Solutions; D008012:Lidocaine; C015358:methylparaben; D002118:Calcium