Fluoroquinolones influence the intracellular calcium handling in individuals susceptible to malignant hyperthermia

Abstract

The mechanisms of fluoroquinolone-induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. An in vitro contracture test used to investigate cellular processes in malignant hyperthermia (MH) can be applied to study the effects of fluoroquinolones. With approval of the local ethics committee, muscle biopsies of 18 MH susceptible (MHS) and 12 MHS non-susceptible (MHN) pigs were performed. Individual bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After equilibration they were exposed to ciprofloxacin or levofloxacin. The measured baseline tension was analyzed (Wilcoxon test: P < 0.05). There were no differences in weight, length, or predrug tension between the groups. Both levofloxacin an ciprofloxacin induced significant contractures in MHS muscle bundles but not in MHN. Fluoroquinolones appear to have a pathological influence on intracellular calcium handling. A pre-existing impairment of the calcium homeostasis, however, seems to be necessary for this behavior.