Cardioprotective Actions of a Glucagon-like Peptide-1 Receptor Agonist on Hearts Donated After Circulatory Death
Background Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia-reperfusion injury. Exenatide, a glucagon-like peptide-1 receptor agonist, manifests protection against cardiac ischemia-reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15-minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5-nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60-120 minutes of reperfusion, P<0.001) and lower cardiac troponin-I release (27.94±11.17 versus 42.25±11.80 mmol/L, P=0.04) during reperfusion compared with controls. In working mode, exenatide-treated hearts showed better diastolic function (dp/dt min: -3644±620 versus -2193±610 mm Hg/s, P<0.001; Tau: 15.62±1.78 versus 24.59±7.35 milliseconds, P=0.02; lateral e' velocity: 11.27 ± 1.46 versus 7.19±2.96, P=0.01), as well as lower venous lactate levels (3.17±0.75 versus 5.17±1.44 mmol/L, P=0.01) compared with controls. Higher levels of activated endothelial nitric oxide synthase (phosphorylated to total endothelial nitric oxide synthase levels: 2.71±1.16 versus 1.37±0.35, P=0.02) with less histological evidence of endothelial damage (von Willebrand factor expression: 0.024±0.007 versus 0.331±0.302, pixel/μm, P=0.04) was also observed with exenatide treatment versus controls. Conclusions Acute treatment of DCD hearts with exenatide limits myocardial and endothelial injury and improves donor cardiac function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Journal of the American Heart Association - 12(2023), 3 vom: 07. Feb., Seite e027163 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kadowaki, Sachiko [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.03.2023 Date Revised 02.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1161/JAHA.122.027163 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352058722 |
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| 100 | 1 | |a Kadowaki, Sachiko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cardioprotective Actions of a Glucagon-like Peptide-1 Receptor Agonist on Hearts Donated After Circulatory Death |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 02.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia-reperfusion injury. Exenatide, a glucagon-like peptide-1 receptor agonist, manifests protection against cardiac ischemia-reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15-minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5-nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60-120 minutes of reperfusion, P<0.001) and lower cardiac troponin-I release (27.94±11.17 versus 42.25±11.80 mmol/L, P=0.04) during reperfusion compared with controls. In working mode, exenatide-treated hearts showed better diastolic function (dp/dt min: -3644±620 versus -2193±610 mm Hg/s, P<0.001; Tau: 15.62±1.78 versus 24.59±7.35 milliseconds, P=0.02; lateral e' velocity: 11.27 ± 1.46 versus 7.19±2.96, P=0.01), as well as lower venous lactate levels (3.17±0.75 versus 5.17±1.44 mmol/L, P=0.01) compared with controls. Higher levels of activated endothelial nitric oxide synthase (phosphorylated to total endothelial nitric oxide synthase levels: 2.71±1.16 versus 1.37±0.35, P=0.02) with less histological evidence of endothelial damage (von Willebrand factor expression: 0.024±0.007 versus 0.331±0.302, pixel/μm, P=0.04) was also observed with exenatide treatment versus controls. Conclusions Acute treatment of DCD hearts with exenatide limits myocardial and endothelial injury and improves donor cardiac function | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a donation after circulatory death heart | |
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| 700 | 1 | |a Siraj, M Ahsan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weiden |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Parker, Marlee |e verfasserin |4 aut | |
| 700 | 1 | |a Nagy, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Steve Fan, Chun-Po |e verfasserin |4 aut | |
| 700 | 1 | |a Runeckles, Kyle |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Junko |e verfasserin |4 aut | |
| 700 | 1 | |a Haller, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Husain, Mansoor |e verfasserin |4 aut | |
| 700 | 1 | |a Honjo, Osami |e verfasserin |4 aut | |
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