Why the study?
The potential cellular mechanism of mepivacaine's myocardial depressant effect observed in papillary muscle had not yet been investigated.
Does mepivacaine reduce calcium transients in isolated murine ventricular cardiomyocytes?
Does mepivacaine reduce calcium transients in isolated murine ventricular cardiomyocytes?
Mepivacaine reduces calcium transients in murine cardiomyocytes by blocking Na+ channels and enhancing reverse mode NCX activity, suggesting a cellular mechanism for its myocardial depressant effect.
May warrant caution with mepivacaine in patients with reduced contractility; leaves open clinical translation from mouse myocytes.
Background The 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 Ca 2+ transient in isolated adult mouse cardiomyocytes. Methods Single ventricular myocytes were enzymatically isolated from wild-type C57Bl/6 mice and loaded with 10 μM fluorescent Ca 2+ indicator Fluo-4-AM to record intracellular Ca 2+ transients upon electrical stimulation. The mepivacaine effects at half-maximal inhibitory concentration (IC 50 ) was determined on calibrated cardiomyocytes’ Ca 2+ transients by non-parametric statistical analyses on biophysical parameters. Combination of mepivacaine with NCX blockers ORM-10103 or NiCl 2 were used to test a possible mechanism to explain mepivacaine-induced Ca 2+ transients’ reduction. Results A significant inhibition at mepivacaine’s IC 50 (50 μM) on Ca 2+ 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 D 50 (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 NiCl 2 showed a significant increase in the baseline of [Ca 2+ ] and arrhythmic activity upon electrical stimulation. Conclusion At cellular level, mepivacaine blocks Na + channels, enhancing the reverse mode activity of NCX, leading to a significant reduction of Ca 2+ transients. These results suggest a new mechanism for the mepivacaine-reduction contractility effect.
No takes yet. Share an insight, caveat, or question.
Mosqueira et al. (2020) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: