Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats
Cardiac arrest is a leading cause of death in the United States and currently, therapeutic hypothermia, now known as targeted temperature management (TTM), is the only recent treatment modality proven to increase survival rates and reduce morbidity for this condition. Shivering and subsequent metabo...
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crwiley:10.1096/fasebj.31.1_supplement.lb605 2024-06-02T08:02:54+00:00 Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats Bailey, Isaac R Laughlin, Bernard Moore, Lucille A Bogren, Lori K Barati, Zeinab Drew, Kelly L National Institutes of Health 2017 http://dx.doi.org/10.1096/fasebj.31.1_supplement.lb605 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor The FASEB Journal volume 31, issue S1 ISSN 0892-6638 1530-6860 journal-article 2017 crwiley https://doi.org/10.1096/fasebj.31.1_supplement.lb605 2024-05-03T10:51:04Z Cardiac arrest is a leading cause of death in the United States and currently, therapeutic hypothermia, now known as targeted temperature management (TTM), is the only recent treatment modality proven to increase survival rates and reduce morbidity for this condition. Shivering and subsequent metabolic stress however, limits application and benefit of TTM. Stimulating CNS A 1 adenosine receptors inhibits shivering and nonshivering thermogenesis in rats and induces a hibernation‐like response in arctic ground squirrels and rats. We found previously that N 6 ‐cyclohexyladenosine (CHA) is more effective at reducing core body temperature (T b ) in dietary restricted (DR) rats than in ad libitum (AL) fed rats. To develop A 1 AR agonists for TTM in AL fed animals, the current study evaluates the effectiveness of dose, drug and ambient temperature (T a ) on the T b lowering effects of CHA and capadenoson in freely fed rats. We found that CHA lowered oxygen consumption (VO 2 ) in AL and DR fed rats, consistent with an inhibition of thermogenesis. CHA at 0.5 or 1.0mg/kg in AL rats produced large variations in response at 17.0°C T a , but after 1.0 mg/kg, IP, all animals cooled to or below a target T b of 32°C; some animals over‐cooled to as low as 21°C but re‐warmed to 37°C without incident at T a 23°C. The partial A 1 AR agonist, capadenoson (1.0 or 2.0mg/kg, IP) produced a consistent response in all animals and decreased T b to a minimum of 36°C from a mean of 38°C at T a 17.0°C during the active phase of the circadian cycle. The response to capadenoson was dose‐dependent . To prevent overcooling after CHA we studied continuous IV administration of CHA in combination with dynamic surface temperature control. Results show this approach to be the best at maintaining a desired target T b . Rigorous optimization of TTM achieved with CHA and dynamic control of conductive cooling will inform future studies aimed at defining the therapeutic benefit of TTM using drugs such as CHA as adjunctive pharmacotherapy. Support or ... Article in Journal/Newspaper Arctic Wiley Online Library Arctic The FASEB Journal 31 S1 |
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Wiley Online Library |
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English |
description |
Cardiac arrest is a leading cause of death in the United States and currently, therapeutic hypothermia, now known as targeted temperature management (TTM), is the only recent treatment modality proven to increase survival rates and reduce morbidity for this condition. Shivering and subsequent metabolic stress however, limits application and benefit of TTM. Stimulating CNS A 1 adenosine receptors inhibits shivering and nonshivering thermogenesis in rats and induces a hibernation‐like response in arctic ground squirrels and rats. We found previously that N 6 ‐cyclohexyladenosine (CHA) is more effective at reducing core body temperature (T b ) in dietary restricted (DR) rats than in ad libitum (AL) fed rats. To develop A 1 AR agonists for TTM in AL fed animals, the current study evaluates the effectiveness of dose, drug and ambient temperature (T a ) on the T b lowering effects of CHA and capadenoson in freely fed rats. We found that CHA lowered oxygen consumption (VO 2 ) in AL and DR fed rats, consistent with an inhibition of thermogenesis. CHA at 0.5 or 1.0mg/kg in AL rats produced large variations in response at 17.0°C T a , but after 1.0 mg/kg, IP, all animals cooled to or below a target T b of 32°C; some animals over‐cooled to as low as 21°C but re‐warmed to 37°C without incident at T a 23°C. The partial A 1 AR agonist, capadenoson (1.0 or 2.0mg/kg, IP) produced a consistent response in all animals and decreased T b to a minimum of 36°C from a mean of 38°C at T a 17.0°C during the active phase of the circadian cycle. The response to capadenoson was dose‐dependent . To prevent overcooling after CHA we studied continuous IV administration of CHA in combination with dynamic surface temperature control. Results show this approach to be the best at maintaining a desired target T b . Rigorous optimization of TTM achieved with CHA and dynamic control of conductive cooling will inform future studies aimed at defining the therapeutic benefit of TTM using drugs such as CHA as adjunctive pharmacotherapy. Support or ... |
author2 |
National Institutes of Health |
format |
Article in Journal/Newspaper |
author |
Bailey, Isaac R Laughlin, Bernard Moore, Lucille A Bogren, Lori K Barati, Zeinab Drew, Kelly L |
spellingShingle |
Bailey, Isaac R Laughlin, Bernard Moore, Lucille A Bogren, Lori K Barati, Zeinab Drew, Kelly L Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats |
author_facet |
Bailey, Isaac R Laughlin, Bernard Moore, Lucille A Bogren, Lori K Barati, Zeinab Drew, Kelly L |
author_sort |
Bailey, Isaac R |
title |
Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats |
title_short |
Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats |
title_full |
Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats |
title_fullStr |
Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats |
title_full_unstemmed |
Dynamic Surface Temperature Control Prevents Overcooling with N 6 ‐Cyclohexyladenosine in Rats |
title_sort |
dynamic surface temperature control prevents overcooling with n 6 ‐cyclohexyladenosine in rats |
publisher |
Wiley |
publishDate |
2017 |
url |
http://dx.doi.org/10.1096/fasebj.31.1_supplement.lb605 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
The FASEB Journal volume 31, issue S1 ISSN 0892-6638 1530-6860 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1096/fasebj.31.1_supplement.lb605 |
container_title |
The FASEB Journal |
container_volume |
31 |
container_issue |
S1 |
_version_ |
1800747375748186112 |