• Brian R Weil, Shannon E Allen, Thomas Barbaccia, Kimberly Wong, Abigail M Beaver, Elizabeth A Slabinski, Jeffrey G Mellott, Peter C Taylor Dickinson, and Shaker A Mousa.
• Department of Physiology & Biophysics, University at Buffalo, Buffalo, NY, USA; the Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Albany, NY, USA; Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, USA; Hematology Unit, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Pro-Al Medico Technologies Inc., Suffern, NY, USA. Electronic address: bweil@buffalo.edu.
• Resuscitation. 2023 May 1; 186: 109735109735.

BackgroundGiven emerging evidence of rapid non-genomic cytoprotective effects of triiodothyronine (T3), we evaluated the resuscitative efficacy of two nanoparticle formulations of T3 (T3np) designed to prolong cell membrane receptor-mediated signaling.MethodsSwine (n = 40) were randomized to intravenous vehicle (empty np), EPI (0.015 mg/kg), T3np (0.125 mg/kg), or T3np loaded with phosphocreatine (T3np + PCr; 0.125 mg/kg) during CPR following 7-min cardiac arrest (n = 10/group). Hemodynamics and biomarkers of heart (cardiac troponin I; cTnI) and brain (neuron-specific enolase; NSE) injury were assessed for up to 4-hours post-ROSC, at which time the heart and brain were collected for post-mortem analysis.ResultsCompared with vehicle (4/10), the rate of ROSC was higher in swine receiving T3np (10/10; p < 0.01), T3np + PCr (8/10; p = 0.08) or EPI (10/10; p < 0.01) during CPR. Although time to ROSC and survival duration were comparable between groups, EPI was associated with a ∼2-fold higher post-ROSC concentration of cTnI vs T3np and T3np + PCr and the early post-ROSC rise in NSE and neuronal injury were attenuated in T3np-treated vs EPI-treated animals. Analysis of hippocampal ultrastructure revealed deterioration of mitochondrial integrity, reduced active zone length, and increased axonal vacuolization in EPI-treated animals vs controls. However, the frequency of these abnormalities was diminished in animals resuscitated with T3np.ConclusionsT3np achieved a ROSC rate and post-ROSC survival that was superior to vehicle and comparable to EPI. The attenuation of selected biomarkers of cardiac and neurologic injury at individual early post-ROSC timepoints in T3np-treated vs EPI-treated animals suggests that T3np administration during CPR may lead to more favorable outcomes in cardiac arrest.Copyright © 2023 Elsevier B.V. All rights reserved.

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