RESULTS: In 24 female pigs, pulseless electrical activity was induced by inflating balloon catheters in the right coronary and left anterior descending arteries for ≈7 minutes. Advanced life support was initiated. In 12 control animals, epinephrine was given after 1 and 3 minutes. In 12 peptide-treated animals, 7.5 mg/kg TAT-PHLPP9c was also administered at 1 and 3 minutes of CPR. The balloons were removed after 2 minutes of support. Animals were recovered and neurologically scored 24 hours after return of spontaneous circulation. Return of spontaneous circulation was more common in the peptide group, but this difference was not significant (8/12 control versus 12/12 peptide; P=0.093), while fully intact neurologic survival was significantly more common in the peptide group (0/12 control versus 11/12 peptide; P<0.00001). TAT-PHLPP9c significantly increased myocardial nicotinamide adenine dinucleotide levels.
CONCLUSIONS: TAT-PHLPP9c resulted in improved survival with full neurologic function after sudden cardiac arrest in a swine model of pulseless electrical activity, and the peptide shows potential as an intra-CPR pharmacologic agent.
结果:在24头雌性猪中,通过在右冠状动脉和左前降支动脉中充气球囊导管≈7分钟,可诱发无脉电活动。启动了高级生命支持。在12只对照动物中,1分钟和3分钟后给予肾上腺素。在12个肽处理的动物中,在CPR的1和3分钟时也施用7.5mg/kgTAT-PHLPP9c。在2分钟的支撑之后移除球囊。恢复动物并在恢复自发循环后24小时进行神经评分。自发循环的恢复在肽组中更为常见,但这种差异并不显著(8/12对照与12/12肽;P=0.093),而完全完整的神经系统生存在肽组中明显更常见(0/12对照对11/12肽;P<0.00001)。TAT-PHLPP9c显著增加心肌烟酰胺腺嘌呤二核苷酸水平。
结论:TAT-PHLPP9c在无脉搏电活动的猪模型中导致心脏骤停后具有完整神经功能的存活率提高,并且该肽显示出作为CPR内药物的潜力。