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Hypothermia After Cardiac Arrest in Large Animals (HACA-LA): Study protocol of a randomized controlled experimental trial

O. Persson, A. Valerianova, J. Bělohlávek, T. Cronberg, N. Nielsen, E. Englund, M. Mlček, H. Friberg

. 2024 ; 19 (-) : 100704. [pub] 20240629

Status not-indexed Language English Country Netherlands

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24017927

BACKGROUND: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. METHODS: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure >60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. CONCLUSION: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest.Trial registration:Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.

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$a BACKGROUND: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. METHODS: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure >60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. CONCLUSION: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest.Trial registration:Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.
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$a Valerianova, Anna $u Third Department of Internal Medicine, General University Hospital, Charles University, Prague, Czech Republic $u Institute of Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Bělohlávek, Jan $u Second Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
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$a Cronberg, Tobias $u Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden $u Department of Neurology, Skåne University Hospital, Lund, Sweden
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$a Nielsen, Niklas $u Department of Clinical Sciences, Anaesthesiology and Intensive Care, Lund University, Lund, Sweden
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$a Englund, Elisabet $u Department of Clinical Sciences, Pathology, Lund University, Lund, Sweden $u Department of Genetics, Pathology and Molecular Diagnostics, Skåne University Hospital, Lund, Sweden
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$a Mlček, Mikuláš $u Institute of Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
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