Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts

Abstract A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (...

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Autores principales:	Marie V. Hjortbak, Nichlas R. Jespersen, Rebekka V. Jensen, Thomas R. Lassen, Johanne Hjort, Jonas A. Povlsen, Nicolaj B. Støttrup, Jakob Hansen, Derek J. Hausenloy, Hans Erik Bøtker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e685b9ead538425484adf0ee95397499
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spelling	oai:doaj.org-article:e685b9ead538425484adf0ee953974992021-12-02T14:12:08ZCardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts10.1038/s41598-020-79449-x2045-2322https://doaj.org/article/e685b9ead538425484adf0ee953974992021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79449-xhttps://doaj.org/toc/2045-2322Abstract A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia.Marie V. HjortbakNichlas R. JespersenRebekka V. JensenThomas R. LassenJohanne HjortJonas A. PovlsenNicolaj B. StøttrupJakob HansenDerek J. HausenloyHans Erik BøtkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marie V. Hjortbak Nichlas R. Jespersen Rebekka V. Jensen Thomas R. Lassen Johanne Hjort Jonas A. Povlsen Nicolaj B. Støttrup Jakob Hansen Derek J. Hausenloy Hans Erik Bøtker Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
description	Abstract A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia.
format	article
author	Marie V. Hjortbak Nichlas R. Jespersen Rebekka V. Jensen Thomas R. Lassen Johanne Hjort Jonas A. Povlsen Nicolaj B. Støttrup Jakob Hansen Derek J. Hausenloy Hans Erik Bøtker
author_facet	Marie V. Hjortbak Nichlas R. Jespersen Rebekka V. Jensen Thomas R. Lassen Johanne Hjort Jonas A. Povlsen Nicolaj B. Støttrup Jakob Hansen Derek J. Hausenloy Hans Erik Bøtker
author_sort	Marie V. Hjortbak
title	Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_short	Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_full	Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_fullStr	Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_full_unstemmed	Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_sort	cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e685b9ead538425484adf0ee95397499
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Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts

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