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

Persson, Olof LU ; Valerianova, Anna ; Tejkl, Leos ; Bělohlávek, Jan ; Cronberg, Tobias LU ; Nielsen, Niklas LU orcid ; Frigyesi, Attila LU ; Ullén, Susann LU ; Weihs, Wolfgang and Stommel, Alexandra Maria , et al. (2025) In Intensive Care Medicine Experimental 13(1).
Abstract

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... (More)

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. Trial registry: Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiac arrest, Functional outcome, Hypothermia, Neurofilament light chain (NfL), Neuronal damage, Swine, Temperature control
in
Intensive Care Medicine Experimental
volume
13
issue
1
article number
105
publisher
Springer Nature
external identifiers
  • scopus:105019577468
  • pmid:41123853
ISSN
2197-425X
DOI
10.1186/s40635-025-00815-y
language
English
LU publication?
yes
id
22ce6263-96eb-46a3-9bd6-efd838884344
date added to LUP
2025-12-10 13:19:06
date last changed
2025-12-11 03:00:07
@article{22ce6263-96eb-46a3-9bd6-efd838884344,
  abstract     = {{<p>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. Trial registry: Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.</p>}},
  author       = {{Persson, Olof and Valerianova, Anna and Tejkl, Leos and Bělohlávek, Jan and Cronberg, Tobias and Nielsen, Niklas and Frigyesi, Attila and Ullén, Susann and Weihs, Wolfgang and Stommel, Alexandra Maria and Blennow, Kaj and Zetterberg, Henrik and Högler, Sandra and Englund, Elisabet and Mlček, Mikuláš and Friberg, Hans}},
  issn         = {{2197-425X}},
  keywords     = {{Cardiac arrest; Functional outcome; Hypothermia; Neurofilament light chain (NfL); Neuronal damage; Swine; Temperature control}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{Intensive Care Medicine Experimental}},
  title        = {{Hypothermia after Cardiac Arrest in Large Animals (HACA-LA) : a randomized controlled experimental study}},
  url          = {{http://dx.doi.org/10.1186/s40635-025-00815-y}},
  doi          = {{10.1186/s40635-025-00815-y}},
  volume       = {{13}},
  year         = {{2025}},
}