A novel pharmacological strategy by PTEN inhibition for improving metabolic resuscitation and survival after mouse cardiac arrest

American Journal of Physiology. Heart and Circulatory Physiology
Jing LiTerry L Vanden Hoek

Abstract

Sudden cardiac arrest (SCA) is a leading cause of death in the United States. Despite return of spontaneous circulation, patients die due to post-SCA syndrome that includes myocardial dysfunction, brain injury, impaired metabolism, and inflammation. No medications improve SCA survival. Our prior work suggests that optimal Akt activation is critical for cooling protection and SCA recovery. Here, we investigate a small inhibitor of PTEN, an Akt-related phosphatase present in heart and brain, as a potential therapy in improving cardiac and neurological recovery after SCA. Anesthetized adult female wild-type C57BL/6 mice were randomized to pretreatment of VO-OHpic (VO) 30 min before SCA or vehicle control. Mice underwent 8 min of KCl-induced asystolic arrest followed by CPR. Resuscitated animals were hemodynamically monitored for 2 h and observed for 72 h. Outcomes included heart pressure-volume loops, energetics (phosphocreatine and ATP from (31)P NMR), protein phosphorylation of Akt, GSK3β, pyruvate dehydrogenase (PDH) and phospholamban, circulating inflammatory cytokines, plasma lactate, and glucose as measures of systemic metabolic recovery. VO reduced deterioration of left ventricular maximum pressure, maximum rate of change i...Continue Reading

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Citations

Feb 2, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rafael Pulido
Aug 2, 2017·The American Journal of Chinese Medicine·Jing LiZuo-Hui Shao
Aug 11, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Taylor A Johnson, Dinender K Singla
Mar 29, 2018·International Journal of Molecular Sciences·Zuohui ShaoJing Li
Mar 28, 2021·Translational Psychiatry·Xiao-Qing WangYu-Qiang Ding
Apr 10, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Xiangdong ZhuTerry L Vanden Hoek
Aug 3, 2021·Cell Regeneration·Tian LiangJinghai Chen
Jun 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhang LiLifang Li

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