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Bupivacaine is frequently used for regional anesthesia and postoperative analgesia. However, an inadvertent intravenous injection can cause severe cardiotoxicity, manifesting as arrhythmia, hypotension, and even cardiac asystole. The mechanism of bupivacaine-mediated cardiotoxicity remains unclear. SK2 knockout mice (SK) and wild-type mice (WT) were divided into four groups, with 12 mice per group. We determined the difference in bupivacaine cardiotoxicity between SK2 knockout and WT mice by measuring the time to the first arrhythmia (Tarrhythmia) and the time to asystole (Tasystole). Secondary indicators of cardiotoxicity were the time from the beginning of bupivacaine infusion to 20% prolongation of the QT interval (TQT) and the time to 20% widening of the QRS complex (TQRS). Tarrhythmia and Tasystole were significantly longer in the SK-bupi group than in the WT-bupi group (both P < 0.05). TQT and TQRS were longer in the SK-bupi group than in the WT-bupi group (all P < 0.05). The time to 25%, 50%, and 75% reduction in HR in the SK-bupi group was significantly longer than in the WT-bupi group (all P < 0.05). Knocking out the SK2 channel can reduce bupivacaine-induced cardiotoxicity in the mouse. [ABSTRACT FROM AUTHOR]

Apelin has been reported to regulate mitochondrial function in myocardial ischemia-reperfusion injury and cerebral ischemia-reperfusion injury. However, the role of apelin-13 in lung ischemia-reperfusion injury (LIRI) remains unclear. This study established an experimental rat model to evaluate the underlying mechanisms of apelin-13 on LIRI. Twenty-four rats were randomly divided to sham operation group (group SM), ischemia/reperfusion group (group IR), and apelin-13 treatment group (group APL). The effects of apelin-13 on LIRI were determined histologically using H&E staining, while the wet/dry weight ratio was used to assess lung edema caused by LIRI. Inflammatory cytokines were also detected in Bronchoalveolar lavage (BAL) fluid by ELISA. The protein expression of UCP2 and the morphological changes of mitochondria were determined by western blotting and electromicroscopy, respectively. The results demonstrated the structural damage of lung tissues and lung edema in group IR. An increased level of inflammatory cytokines including IL-1β, IL-6 and TNF-α was observed in rats with LIRI using ELISA. After that, oxidative stress and morphological damage of mitochondria were also shown in group IR. Yet, the application of apelin-13 reversed all these deleterious effects in group APL. The protective effects of apelin-13 were indicated by decreased reactive oxygen species (ROS) and elevated UCP2 expression levels in rats. In conclusion, this study revealed that apelin-13 had protective effects against LIRI via attenuating lung edema, the production of inflammatory cytokines, oxidative stress and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]