Hypothermia after Cardiac Arrest in Large Animals (HACA-LA): a randomized controlled experimental study

Title (eng)
Hypothermia after Cardiac Arrest in Large Animals (HACA-LA): a randomized controlled experimental study
Author
Olof Persson
Author
Anna Valerianova
Author
Leos Tejkl
Author
Jan Bělohlávek
Author
Tobias Cronberg
Author
Niklas Nielsen
Author
Attila Frigyesi
Author
Susann Ullén
Author
Wolfgang Weihs
Author
Alexandra-Maria Stommel
Author
Kaj Blennow
Author
Henrik Zetterberg
Author
Sandra Högler
Author
Elisabet Englund
Author
Mikuláš Mlček
Author
Hans Friberg
Abstract (eng)
Background Induced hypothermia after cardiac arrest is neuroprotective in several animal models of cardiac arrest, but few high-quality studies have been conducted in larger animals. Recent clinical trials have questioned the beneficial effects of post-ischemic hypothermia. This study investigated whether immediate cooling or a 2-h delay in cooling to 33 °C after cardiac arrest was neuroprotective compared to controlled normothermia in large animals. Methods Young adult female swine were anesthetized and kept at normothermia (38 °C). All animals were subject to 10 min of cardiac arrest by ventricular fibrillation, followed by 4 min of cardiopulmonary resuscitation, before the first countershock. At 10 min of return of spontaneous circulation (ROSC), animals were included and randomized to receive immediate hypothermia (33 °C), 2-h delayed hypothermia (33 °C), or normothermia for 30 h, including both cooling and rewarming time. Animals were extubated and assessed for 7 days. The primary outcome was brain histopathology using a modified Histology Damage Score. Secondary outcomes were neurocognitive testing, neurologic deficit score, and biomarkers of brain injury. Results Among 42 animals, 33 were included; 11 in each arm, 23 survived until day 7. The modified Histology Damage Score was not significantly different between groups (p = 0.29). Neither neurocognitive testing nor neurologic deficit scores showed significant differences between the groups (p = 0.11 and p = 0.67, respectively). Neurofilament light chain (NfL) levels were significantly lower in the immediate hypothermia group at 48 h and on day 7 compared to the normothermia group (p = 0.0087, p = 0.012), but not in the delayed hypothermia group (p = 0.075, p = 0.33). Conclusion Our experimental model in large swine showed no neuropathological or functional protective effect of induced hypothermia after cardiac arrest, but NfL levels were lower in animals receiving immediately induced hypothermia, suggesting mitigation of neuronal injury.
Keywords (eng)
Cardiac ArrestHypothermiaTemperature ControlNeuronal DamageFunctional OutcomeNeurofilament Light Chain (NfL)Swine
Type (eng)
journal article
Language
[eng]
Persistent identifier
https://phaidra.vetmeduni.ac.at/o:5116
DOI
10.1186/s40635-025-00815-y
Is in series
Title (eng)
Intensive Care Medicine Experimental
Volume
13
Issue
1
ISSN
2197-425X
Issued
2025
Number of pages
12
Publication
Springer
Version type (eng)
version of record (published version)
Date issued
2025
Access rights (eng)
open access
License
CC BY 4.0 International
Rights statement (eng)
© 2025, The Author(s)