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Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In Vitro
- Source :
- Anesthesia & Analgesia. 122:418-423
- Publication Year :
- 2016
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2016.
-
Abstract
- Local anesthetics, especially bupivacaine, have myotoxic effects in clinically used concentrations and context. Detailed mechanisms of these effects are unknown, but an increase in intracellular calcium levels is suspected to be the most important trigger. Dantrolene and caffeine modify cellular calcium release from the sarcoplasmic reticulum. The aim of our study was to investigate the effect of dantrolene and caffeine on bupivacaine-induced myotoxicity in vitro.A cell culture model of primary muscle cells of BALB/c AnNCrl mice was established. Cells were incubated simultaneously with increasing concentrations of bupivacaine, dantrolene, and caffeine. The fraction of dead cells was calculated after staining with propidium iodide and analysis by flow cytometry. The half-maximal inhibitory concentration of bupivacaine was calculated for each concentration. Group differences were determined by using 1-way analysis of variances with subsequent post hoc 1-way Dunnett t test.Both dantrolene and caffeine alone had no effect on muscle cell survival. Increasing concentrations of bupivacaine caused increasing cell death. Dantrolene dose-dependently reduced the fraction of necrotic cells, whereas caffeine dose-dependently increased the fraction of dead cells.Dantrolene attenuated, and caffeine enhanced, bupivacaine-induced myotoxicity, presumably by modifying sarcoplasmic calcium release. This indicates that intracellular calcium release is an important factor for local anesthetic-induced cell death.
- Subjects :
- Dantroleno
medicine.medical_specialty
Annexins
Myotoxin
Primary Cell Culture
Context (language use)
In Vitro Techniques
Pharmacology
Dantrolene
Calcium in biology
Mice
Necrosis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Muscular Diseases
030202 anesthesiology
Caffeine
medicine
Animals
Anesthetics, Local
Bupivacaine
Mice, Inbred BALB C
Muscle Relaxants, Central
business.industry
In vitro
Surgery
Anesthesiology and Pain Medicine
chemistry
Central Nervous System Stimulants
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 00032999
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Anesthesia & Analgesia
- Accession number :
- edsair.doi.dedup.....9a0f562aa984c455ef06efd7518b1170