Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model
Resuscitation Plus | July 20, 2024
Senthil K, Ranganathan A, Piel S, Hefti MM, Reeder RW, Kirschen MP, Starr J, Morton S, Gaudio HA, Slovis JC, Herrmann JR, Berg RA, Kilbaugh TJ, Morgan RW.
Resusc Plus. 2024
https://doi.org/10.1016/j.resplu.2024.100726
Abstract
Introduction
Swine exhibit cerebral cortex mitochondrial dysfunction and neuropathologic injury after hypoxic cardiac arrest treated with hemodynamic-directed CPR (HD-CPR) despite normal Cerebral Performance Category scores. We analyzed the temporal evolution of plasma protein biomarkers of brain injury and inflammatory cytokines, as well as cerebral cortical mitochondrial injury and neuropathology for five days following pediatric asphyxia-associated cardiac arrest treated with HD-CPR.
Methods
One-month-old swine underwent asphyxia associated cardiac arrest, 10–20 min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20 mmHg), and randomization to post-ROSC survival duration (24, 48, 72, 96, 120 h; n = 3 per group) with standardized post-resuscitation care. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokine levels were collected pre-injury and 1, 6, 24, 48, 72, 96, and 120 h post-ROSC. Cerebral cortical tissue was assessed for: mitochondrial respirometry, mass, and dynamic proteins; oxidative injury; and neuropathology.
Results
Relative to pre-arrest baseline (9.4 pg/ml [6.7–12.6]), plasma NfL was increased at all post-ROSC time points. Each sequential NfL measurement through 48 h was greater than the previous value {1 h (12.7 pg/ml [8.4–14.6], p = 0.01), 6 h (30.9 pg/ml [17.7–44.0], p = 0.0004), 24 h (59.4 pg/ml [50.8–96.1], p = 0.0003) and 48 h (85.7 pg/ml [61.9–118.7], p = 0.046)}. Plasma GFAP, inflammatory cytokines or cerebral cortical tissue measurements were not demonstrably different between time points.
Conclusions
In a swine model of pediatric cardiac arrest, plasma NfL had an upward trajectory until 48 h post-ROSC after which it remained elevated through five days, suggesting it may be a sensitive marker of neurologic injury following pediatric cardiac arrest.