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Mild hypothermia attenuates ischemia/reperfusion injury - insights from serial non-invasive pressure-volume loops

Berg, Jonathan LU orcid ; Jablonowski, Robert LU ; Nordlund, David LU ; Ryd, Daniel LU ; Heiberg, Einar LU orcid ; Carlsson, Marcus LU and Arheden, Håkan LU (2023) In Cardiovascular Research 119(12). p.2230-2243
Abstract

BACKGROUND: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analyzed cardiac performance in a porcine model of ischemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout one week using non-invasive pressure-volume loops.

METHODS AND RESULTS: Normothermia and Hypothermia groups sessions (n=7+7 pigs, nonrandom allocation) were imaged with CMR at baseline and subjected to 40 minutes of normothermic ischemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 minutes before... (More)

BACKGROUND: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analyzed cardiac performance in a porcine model of ischemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout one week using non-invasive pressure-volume loops.

METHODS AND RESULTS: Normothermia and Hypothermia groups sessions (n=7+7 pigs, nonrandom allocation) were imaged with CMR at baseline and subjected to 40 minutes of normothermic ischemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 minutes before reperfusion. Additional CMR sessions at two hours, 24 hours, and seven days acquired ventricular volumes and ischemic injuries (unblinded analysis).Stroke volume (-24%; p=0.029; Friedmans test) and ejection fraction (-20%; p=0.068) were notably reduced at 24h in the Normothermia group compared to baseline. In contrast, the decreases were ameliorated in the Hypothermia group (stroke volume: -6%; p=0.77; ejection fraction: -6%; p=0.13). Mean arterial pressure remained stable in Normothermic animals (-3%, p=0.77) but dropped two hours post-reperfusion in hypothermic animals (-18%, p=0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over one week, but the adverse effects tended attenuated in the Hypothermia group. Infarct sizes were 10±8% in Hypothermic and 15±8% in Normothermic animals (p=0.32). Analysis of covariance at 24 hours indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (p=0.061) and lower arterial elastance (p=0.015).

CONCLUSION: Using non-invasive pressure-volume loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart's work after ischemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cardiovascular Research
volume
119
issue
12
pages
2230 - 2243
publisher
Oxford University Press
external identifiers
  • pmid:36734080
  • scopus:85163417225
ISSN
1755-3245
DOI
10.1093/cvr/cvad028
language
English
LU publication?
yes
additional info
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
id
7d10ea8c-a7ba-4731-96b3-74b8f1dd129e
date added to LUP
2023-02-24 08:25:56
date last changed
2025-10-19 12:44:00
@article{7d10ea8c-a7ba-4731-96b3-74b8f1dd129e,
  abstract     = {{<p>BACKGROUND: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analyzed cardiac performance in a porcine model of ischemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout one week using non-invasive pressure-volume loops.</p><p>METHODS AND RESULTS: Normothermia and Hypothermia groups sessions (n=7+7 pigs, nonrandom allocation) were imaged with CMR at baseline and subjected to 40 minutes of normothermic ischemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 minutes before reperfusion. Additional CMR sessions at two hours, 24 hours, and seven days acquired ventricular volumes and ischemic injuries (unblinded analysis).Stroke volume (-24%; p=0.029; Friedmans test) and ejection fraction (-20%; p=0.068) were notably reduced at 24h in the Normothermia group compared to baseline. In contrast, the decreases were ameliorated in the Hypothermia group (stroke volume: -6%; p=0.77; ejection fraction: -6%; p=0.13). Mean arterial pressure remained stable in Normothermic animals (-3%, p=0.77) but dropped two hours post-reperfusion in hypothermic animals (-18%, p=0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over one week, but the adverse effects tended attenuated in the Hypothermia group. Infarct sizes were 10±8% in Hypothermic and 15±8% in Normothermic animals (p=0.32). Analysis of covariance at 24 hours indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (p=0.061) and lower arterial elastance (p=0.015).</p><p>CONCLUSION: Using non-invasive pressure-volume loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart's work after ischemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.</p>}},
  author       = {{Berg, Jonathan and Jablonowski, Robert and Nordlund, David and Ryd, Daniel and Heiberg, Einar and Carlsson, Marcus and Arheden, Håkan}},
  issn         = {{1755-3245}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{12}},
  pages        = {{2230--2243}},
  publisher    = {{Oxford University Press}},
  series       = {{Cardiovascular Research}},
  title        = {{Mild hypothermia attenuates ischemia/reperfusion injury - insights from serial non-invasive pressure-volume loops}},
  url          = {{http://dx.doi.org/10.1093/cvr/cvad028}},
  doi          = {{10.1093/cvr/cvad028}},
  volume       = {{119}},
  year         = {{2023}},
}