Affiliation:
1. the First Affiliated Hospital of Wenzhou Medical University
2. the Affiliated Stomatological Hospital of Nanjing Medical University
3. Sir Run Run Shaw Hospital
4. Second Affiliated Hospital of Zhejiang University
5. the Ohio State University Wexner Medical Center
6. Independent researcher
Abstract
Abstract
Backgrounds
Abnormal energy metabolism is an important mechanism in bupivacaine-induced cardiotoxicity. Apelin, an adipocyte-derived peptide involved in energy metabolism and regulation of the cardiovascular system, may be linked to bupivacaine-induced cardiotoxicity. Here we investigated the role of apelin in bupivacaine-induced cardiotoxicity and its relationship with energy metabolism.
Methods
We used both an ex vivo Sprague-Dawley (SD) neonatal rat cardiomyocyte toxicity model and an in vivo bupivacaine-induced rat asystole model to investigate the effect and mechanism of exogenous [Pyr1]apelin-13 in bupivacaine-induced cardiotoxicity.
Results
Exogenous [Pyr1]apelin-13 (22 μM) prevented bupivacaine-induced (90 μM) inhibition of the cardiomyocyte beating frequency (mean difference: 0.48, 95% CI: 0.35 to 0.62 versus C-bupi, p<0.001, n=5) in cells treated with bupivacaine for 60 minutes, preserved the mitochondrial ultrastructure and regulated the oxygen consumption rate , and these effects were inhibited by APJ shRNA. Exogenous [Pyr1]apelin-13 (150 μg·kg-1) increased the survival rate of SD rats with bupivacaine-induced (30 mg·kg-1) asystole (12/12 (100%) versus 6/12 (50%), p=0.014), while F13A (150 μg·kg-1), an APJ antagonist, abolished this response (3/12 (25%)). Apelin also increased the expression of adenosine monophosphate-activated protein kinase, acetyl Co-A carboxylase, and peroxisome proliferator-activated receptor-gamma coactivator-1α in SD rats heart tissue.
Conclusion
Exogenous [Pyr1]apelin-13 prevented bupivacaine-induced cardiotoxicity via the receptor APJ in adult male SD rats and SD neonatal rat cardiomyocytes through the preservation of mitochondrial structure and function.
Publisher
Research Square Platform LLC