title: Evaluation of the cardiotoxicity and resuscitation of rats of a newly developed mixture of a QX-314 analog and levobupivacaine.
abstract: OBJECTIVE
  This study was designed to evaluate the cardiotoxicity of a QX-314 analog (QX-OH) and a mixture of QX-OH and levobupivacaine (LL-1) and to compare the ability to resuscitate rats after asystole induced by levobupivacaine (Levo-BUP), QX-314, QX-OH, and LL-1.
  
  
  METHODS
  First, we used the "up-and-down" method to determine median dose resulting in appearance of cardiotoxicity (CD50C) and asystole (CD50A) of Levo-BUP, QX-314, QX-OH, and LL-1 in rats. Safety index (SI; ratio of CD50Ccompared with 2-fold median effective dose needed to produce sensory blockade) of the 4 drugs was calculated. Isobolograms were used for drug interaction analysis. Second, rats received 1.2-fold CD50Ain the 4 groups. When asystole occurred, standard cardiopulmonary resuscitation was started and continued for 30 min or until return of spontaneous circulation (ROSC) with native rate-pressure product ≥30% baseline for 5 min.
  
  
  RESULTS
  Ranking of CD50Cwas Levo-BUP < QX-314 ≈ QX-OH. Ranking of CD50Awas Levo-BUP < QX-314 < QX-OH. However, the SI of Levo-BUP was significantly higher than that of QX-314 (10.60 vs. 1.20) or QX-OH (10.60 vs. 1.44). The SI of LL-1 was similar to that of Levo-BUP. Nonsynergistic interaction was observed for cardiac effects between QX-OH and Levo-BUP. ROSC was attained initially by 8 of 8 rats in the Levo-BUP group, 3 of 8 in the QX-314 group, 6 of 8 in the QX-OH group, and 8 of 8 in the LL-1 group. Sustained recovery was achieved in the Levo-BUP group but not in the other groups.
  
  
  CONCLUSIONS
  Levo-BUP and LL-1 are safer than QX-314 or QX-OH. Cardiac effects between QX-OH and Levo-BUP were nonsynergistic. Initial successful resuscitation could be achieved in the QX-OH- and LL-1-induced asystole, but advanced life support might be needed.
authors.affiliation: Department of Anesthesiology.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Ke
authors.affiliation: Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Linghui
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology; Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology; Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
keywords: QX-314; QX-OH; asystole; cardiotoxicity; levobupivacaine