Abstract Body: INTRODUCTION
Biomarker studies in out-of-hospital cardiac arrest (OHCA) have largely focused on prognostication ≥24 hours after cardiac arrest. We hypothesized that early measurement of UCH-L1 and GFAP after return of spontaneous circulation (ROSC) would be feasible in both swine and prehospital OHCA patients, serving as potential indicators of brain injury severity.

METHODS
Swine Model: Thirty-nine Yorkshire swine (50–60 kg) were randomized to sham (n=9), 5-min ventricular fibrillation (VF-5, n=15), or 10-min VF (VF-10, n=15), followed by ACLS to ROSC. Standardized post-cardiac arrest care was provided for 24 hours. Plasma UCH-L1 and GFAP were quantified at baseline, ROSC, 6, 12, 18, and 24 hours using the Alinity TBI iSTAT plasma assay. Longitudinal biomarker changes were assessed via linear mixed-effects modeling.

Prehospital OHCA Patients: The East Anglian Air Ambulance (UK) implemented prehospital UCH-L1 and GFAP testing (Alinity iSTAT whole blood TBI assay) in January 2025. Nine non-traumatic OHCA patients were analyzed.

RESULTS
Swine Models (Figure 1 and Table 1): Mean CPR duration was 10.7±4.6 min in VF-5 and 8.3±4.3 min in VF-10. Plasma UCH-L1 varied significantly over time, with different temporal patterns observed between VF groups and sham controls. Plasma UCH-L1 increased significantly at ROSC vs. baseline (p<0.001) and vs. sham (p<0.005). VF-5 animals showed normalization by 12 hours; VF-10 animals demonstrated a secondary rise at 12 hours. Sham animals showed no significant UCH-L1 changes. GFAP was undetectable, possibly due to structural differences at antibody binding sites.

Prehospital OHCA patients (Table 2): Mean patient age was 63.1±16.7 years. Mean arrest-to-ROSC time was 30±9 min; mean ROSC-to-test time was 51±26 min. All patients exhibited elevated whole blood UCH-L1. Two patients with intracranial hemorrhage had GFAP >3000 pg/mL. Two patients survived to 30 days.

CONCLUSIONS
Early, prehospital measurement of brain injury biomarkers is feasible after OHCA. In swine, UCH-L1 exhibited temporal dynamics suggestive of biphasic elevation after more prolonged cardiac arrest. GFAP kinetics merit exploration using alternative assays. Further clinical studies are warranted to validate UCH-L1 and GFAP as prehospital indicators of neurological injury.