Survival and Neurologic Outcomes From Pharmacologic Peptide Administration During Cardiopulmonary Resuscitation of Pulseless Electrical Activity

• Published in: Journal of the American Heart Association Vol. 13; no. 13; p. e9757
• Main Authors: Oberdier, Matt T, Li, Jing, Ambinder, Daniel I, Suzuki, Masahito, Tumarkin, Ethan, Fink, Sarah, Neri, Luca, Zhu, Xiangdong, Justice, Cody N, Vanden Hoek, Terry L, Halperin, Henry R
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 02.07.2024; Wiley
• Subjects: Akt pathway; Animals; cardiac arrest; Cardiopulmonary Resuscitation - methods; cooling; Disease Models, Animal; drug; Female; Heart Arrest - drug therapy; Heart Arrest - physiopathology; Heart Arrest - therapy; Original Research; Peptides - administration & dosage; Peptides - pharmacology; pharmaceutic; Swine; TAT‐PHLPP9c; Time Factors; cooling; pharmaceutic; TAT‐PHLPP9c; Akt pathway; cardiac arrest; drug
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.123.033371

Outcomes from cardiopulmonary resuscitation (CPR) following sudden cardiac arrest are suboptimal. Postresuscitation targeted temperature management has been shown to have benefit in subjects with sudden cardiac arrest due to ventricular fibrillation, but there are few data for outcomes from sudden cardiac arrest due to pulseless electrical activity. In addition, intra-CPR cooling is more effective than postresuscitation cooling. Physical cooling is associated with increased protein kinase B activity. Therefore, our group developed a novel peptide, TAT-PHLPP9c, which regulates protein kinase B. We hypothesized that when given during CPR, TAT-PHLPP9c would improve survival and neurologic outcomes following pulseless electrical activity arrest. 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; =0.093), while fully intact neurologic survival was significantly more common in the peptide group (0/12 control versus 11/12 peptide; <0.00001). TAT-PHLPP9c significantly increased myocardial nicotinamide adenine dinucleotide levels. 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.