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. 2021 Jul 15;16(1):1070-1075.
doi: 10.1515/med-2021-0311. eCollection 2021.

Dexmedetomidine may decrease the bupivacaine toxicity to heart

Zhousheng Jin  1 , Fangfang Xia  2 , Tingting Lin  2 , Yaoyao Cai  2 , Hongfei Chen  2 , Yuelan Wang  1
Affiliations

Dexmedetomidine may decrease the bupivacaine toxicity to heart

Zhousheng Jin et al. Open Med (Wars). .

Abstract

Objective: The purpose of our study was to explore the effect of dexmedetomidine on cardiac tolerance to bupivacaine.

Method: Human coronary endothelial cells were used to establish in vitro model. They were randomly divided into control (Con) group, dexmedetomidine (Dex) group, bupivacaine (Bupi) group, dexmedetomidine + bupivacaine group (DB group), and dexmedetomidine + bupivacaine + PI3K inhibitor (DB-inhibitor) group. Cell activity was measured by Cell counting kit-8 (CCK-8). Transwell was used to detect cell permeability. Western blotting was used to detect the protein expression of related factors.

Results: There were no notable differences in cell activity among the five groups (P > 0.05). Dexmedetomidine significantly reduced the permeability of endothelial cells to bupivacaine and increased the protein expression of Zonulaoeeludens-1 (ZO-1) (P < 0.01). However, the aforementioned effects of dexmedetomidine were disappeared after the addition of PI3K inhibitors. Furthermore, Dex and DB markedly increased the protein expression of PI3K, p-Akt, and p-PTEN in comparison with Con group (P < 0.001), but there was no significant difference in p-PTEN among DB-inhibitor, Con, and Bupi groups (P > 0.05).

Conclusion: Dex reduced Bupi-induced vasopermeability through protein expression of ZO-1 and PI3K/Akt pathway, which may lead to the decrease of Bupi-induced cardiotoxicity.

Keywords: PI3K/Akt pathway; ZO-1; bupivacaine; cardiac tolerance; dexmedetomidine.

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Conflict of interest statement

Conflict of interest: All authors declare that they have no conflict of interest

Figures

Figure 1
Figure 1
CCK-8 assay for detection of cell viability. Data were expressed as mean ± SD.
Figure 2
Figure 2
Bupivacaine concentration in Transwell lower chamber at 2 h. Bupivacaine concentration in DB group was significantly lower than that in other two groups (Bupi vs DB, P = 0.002, DB-inhibitor vs DB, P = 0.001). There was no statistical difference between Bupi group and DB inhibitor group (P = 0.751). *P < 0.05 vs DB group.
Figure 3
Figure 3
ZO-1 protein expression. The protein expression levels of ZO-1 in DB group and Dex group was higher than that in other three groups. *P < 0.05 vs Con, Bupi, and DB inhibitor.
Figure 4
Figure 4
The protein expression of related factors in the PI3K/Akt pathway. PI3K and p-Akt protein levels in DB group and Dex group were higher than that in other three groups. The expression of p-PTEN in DB group and Dex group was lower than that in other three groups. There was no significant difference in the expression of Akt and PTEN between the two groups. *P < 0.05 vs Con, Bupi, and DB inhibitor.
See this image and copyright information in PMC

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