Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest
Hibernating mammals offer an intriguing example of natural adaptation to physiologic extremes, illustrating mechanisms of metabolic rate depression and cell preservation strategies. Using a model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground s...
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Ovid Technologies (Wolters Kluwer Health)
2011
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Online Access: | http://dx.doi.org/10.1161/circ.124.suppl_21.a17046 |
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crovidcr:10.1161/circ.124.suppl_21.a17046 2024-06-23T07:50:46+00:00 Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest Podgoreanu, Mihai V Ma, Qing Mackensen, G. B Zhang, Zhiquan Smith, Michael P Bain, James Newgard, Christopher B Kohl, Franziska Drew, Kelly L Barnes, Brian M 2011 http://dx.doi.org/10.1161/circ.124.suppl_21.a17046 en eng Ovid Technologies (Wolters Kluwer Health) Circulation volume 124, issue suppl_21 ISSN 0009-7322 1524-4539 journal-article 2011 crovidcr https://doi.org/10.1161/circ.124.suppl_21.a17046 2024-06-04T06:02:21Z Hibernating mammals offer an intriguing example of natural adaptation to physiologic extremes, illustrating mechanisms of metabolic rate depression and cell preservation strategies. Using a model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground squirrels (AGS) display reduced myocardial injury following I/R compared to a non-hibernator (rat) by preservation of PPARα nuclear receptor induced myocardial fatty acid utilization. Methods: Euthermic AGS aroused from hibernation and BN rats underwent either DHCA (45min, followed by 3, 6, or 24h of reperfusion) or sham. The following parameters were compared between species/time points by two-way ANOVA: 1) biochemical severity of myocardial injury (plasma HFABP, TnI, ELISA); 2) myocardial PPARα activity (ELISA) and levels of 167 metabolites (MS); 3) myocardial inflammation and leukocyte extravasation (ELISA). Results: Compared to rats, AGS displayed robust myocardial ischemic tolerance following DHCA. This was accompanied by preservation of myocardial PPARα activity in AGS, which was significantly downregulated in the rat. Organic and amino acid acid profiles suggested compromised citric acid cycle flux, enhanced urea cycle, and myocardial accumulation of dicarboxylacylcarnitines in rats vs AGS. Furthermore, myocardial inflammation was robustly attenuated in AGS vs rat (Table). Conclusion: In the first study assessing myocardial ischemic tolerance in AGS following in vivo global I/R injury, we found an association between the hibernator cardioprotective phenotype and specific differences in myocardial fuel utilization. These findings challenge the current paradigm for metabolic optimization in human myocardial I/R and heart failure, which involves promotion of glucose oxidation at the expense of fatty acid oxidation during early reperfusion by inducing an “adaptive” substrate switch opposite to that demonstrated by natural hibernators. Article in Journal/Newspaper Arctic Ovid Arctic Circulation 124 suppl_21 |
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Hibernating mammals offer an intriguing example of natural adaptation to physiologic extremes, illustrating mechanisms of metabolic rate depression and cell preservation strategies. Using a model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground squirrels (AGS) display reduced myocardial injury following I/R compared to a non-hibernator (rat) by preservation of PPARα nuclear receptor induced myocardial fatty acid utilization. Methods: Euthermic AGS aroused from hibernation and BN rats underwent either DHCA (45min, followed by 3, 6, or 24h of reperfusion) or sham. The following parameters were compared between species/time points by two-way ANOVA: 1) biochemical severity of myocardial injury (plasma HFABP, TnI, ELISA); 2) myocardial PPARα activity (ELISA) and levels of 167 metabolites (MS); 3) myocardial inflammation and leukocyte extravasation (ELISA). Results: Compared to rats, AGS displayed robust myocardial ischemic tolerance following DHCA. This was accompanied by preservation of myocardial PPARα activity in AGS, which was significantly downregulated in the rat. Organic and amino acid acid profiles suggested compromised citric acid cycle flux, enhanced urea cycle, and myocardial accumulation of dicarboxylacylcarnitines in rats vs AGS. Furthermore, myocardial inflammation was robustly attenuated in AGS vs rat (Table). Conclusion: In the first study assessing myocardial ischemic tolerance in AGS following in vivo global I/R injury, we found an association between the hibernator cardioprotective phenotype and specific differences in myocardial fuel utilization. These findings challenge the current paradigm for metabolic optimization in human myocardial I/R and heart failure, which involves promotion of glucose oxidation at the expense of fatty acid oxidation during early reperfusion by inducing an “adaptive” substrate switch opposite to that demonstrated by natural hibernators. |
format |
Article in Journal/Newspaper |
author |
Podgoreanu, Mihai V Ma, Qing Mackensen, G. B Zhang, Zhiquan Smith, Michael P Bain, James Newgard, Christopher B Kohl, Franziska Drew, Kelly L Barnes, Brian M |
spellingShingle |
Podgoreanu, Mihai V Ma, Qing Mackensen, G. B Zhang, Zhiquan Smith, Michael P Bain, James Newgard, Christopher B Kohl, Franziska Drew, Kelly L Barnes, Brian M Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest |
author_facet |
Podgoreanu, Mihai V Ma, Qing Mackensen, G. B Zhang, Zhiquan Smith, Michael P Bain, James Newgard, Christopher B Kohl, Franziska Drew, Kelly L Barnes, Brian M |
author_sort |
Podgoreanu, Mihai V |
title |
Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest |
title_short |
Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest |
title_full |
Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest |
title_fullStr |
Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest |
title_full_unstemmed |
Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest |
title_sort |
abstract 17046: the hibernator metabolic phenotype is cardioprotective in the setting of deep hypothermic circulatory arrest |
publisher |
Ovid Technologies (Wolters Kluwer Health) |
publishDate |
2011 |
url |
http://dx.doi.org/10.1161/circ.124.suppl_21.a17046 |
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Arctic |
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Arctic |
genre |
Arctic |
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Arctic |
op_source |
Circulation volume 124, issue suppl_21 ISSN 0009-7322 1524-4539 |
op_doi |
https://doi.org/10.1161/circ.124.suppl_21.a17046 |
container_title |
Circulation |
container_volume |
124 |
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suppl_21 |
_version_ |
1802641679876882432 |