Mild hypothermia attenuates ischemia/reperfusion injury - insights from serial non-invasive pressure-volume loops
(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.
(Less)
- author
- Berg, Jonathan LU ; Jablonowski, Robert LU ; Nordlund, David LU ; Ryd, Daniel LU ; Heiberg, Einar LU ; Carlsson, Marcus LU and Arheden, Håkan LU
- organization
- publishing date
- 2023-02-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cardiovascular Research
- volume
- 119
- issue
- 12
- pages
- 2230 - 2243
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85163417225
- pmid:36734080
- 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
- 2024-04-19 00:39:08
@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}}, }