Abstract
AbstractBackgroundThe potential mechanism of mepivacaine’s myocardial depressant effect observed in papillary muscle has not yet been investigated at cellular level. Therefore, we evaluated mepivacaine’s effects on Ca2+transient in isolated adult mouse cardiomyocytes.MethodsSingle ventricular myocytes were enzymatically isolated from wild-type C57Bl/6 mice and loaded with 10 μM fluorescent Ca2+indicator Fluo-4-AM to record intracellular Ca2+transients upon electrical stimulation. The mepivacaine effects at half-maximal inhibitory concentration (IC50) was determined on calibrated cardiomyocytes’ Ca2+transients by non-parametric statistical analyses on biophysical parameters. Combination of mepivacaine with NCX blockers ORM-10103 or NiCl2were used to test a possible mechanism to explain mepivacaine-induced Ca2+transients’ reduction.ResultsA significant inhibition at mepivacaine’s IC50(50 μM) on Ca2+transients was measured in biophysical parameters such as peak (control: 528.6 ± 73.61 nM vs mepivacaine: 130.9 ± 15.63 nM;p < 0.05), peak area (control: 401.7 ± 63.09 nM*s vs mepivacaine: 72.14 ± 10.46 nM*s;p < 0.05), slope (control: 7699 ± 1110 nM/s vs mepivacaine: 1686 ± 226.6 nM/s;p < 0.05), time to peak (control: 107.9 ± 8.967 ms vs mepivacaine: 83.61 ± 7.650 ms; p < 0.05) and D50(control: 457.1 ± 47.16 ms vs mepivacaine: 284.5 ± 22.71 ms; p < 0.05). Combination of mepivacaine with NCX blockers ORM-10103 or NiCl2showed a significant increase in the baseline of [Ca2+] and arrhythmic activity upon electrical stimulation.ConclusionAt cellular level, mepivacaine blocks Na+channels, enhancing the reverse mode activity of NCX, leading to a significant reduction of Ca2+transients. These results suggest a new mechanism for the mepivacaine-reduction contractility effect.
Funder
Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
Subject
Anesthesiology and Pain Medicine
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