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[Effects of 4-hydroxybenzoic Acid Methyl Ester on the Ca(2+)-related Functions of Skinned Skeletal Muscle Fibers From the Guinea Pig]

[Effects of 4-hydroxybenzoic Acid Methyl Ester on the Ca(2+)-related Functions of Skinned Skeletal Muscle Fibers From the Guinea Pig]

M Nagasawa

Masui. 2000 Apr;49(4):369-75.

PMID: 10793521

Abstract:

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.

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