Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario
IntroductionDiazoxide is a powerful cardioprotective agent that activates mitochondrial ATP-dependent K-channels and stimulates mitochondrial respiration. Diazoxide reduced infarct size in isolated rodent heart preparations and upon pretreatment in juvenile pigs with coronary occlusion/reperfusion....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1173462/full |
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| author | Petra Kleinbongard Helmut Lieder Andreas Skyschally Gerd Heusch |
| author_facet | Petra Kleinbongard Helmut Lieder Andreas Skyschally Gerd Heusch |
| author_sort | Petra Kleinbongard |
| collection | DOAJ |
| description | IntroductionDiazoxide is a powerful cardioprotective agent that activates mitochondrial ATP-dependent K-channels and stimulates mitochondrial respiration. Diazoxide reduced infarct size in isolated rodent heart preparations and upon pretreatment in juvenile pigs with coronary occlusion/reperfusion. We aimed to study the use of diazoxide in a more realistic adult pig model of reperfused acute myocardial infarction when diazoxide was administered just before reperfusion.Methods and resultsIn a first approach, we pretreated anaesthetised adult Göttingen minipigs with 7 mg kg−1 diazoxide (n = 5) or placebo (n = 5) intravenously over 10 min and subjected them to 60 min coronary occlusion and 180 min reperfusion; blood pressure was maintained by use of an aortic snare. The primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was the secondary endpoint. In a second approach, diazoxide (n = 5) was given from 50 to 60 min coronary occlusion, and blood pressure was not maintained. There was a significant reduction in infarct size (22% ± 11% of area at risk with diazoxide pretreatment vs. 47% ± 11% with placebo) and area of no-reflow (14% ± 14% of infarct size with diazoxide pretreatment vs. 46% ± 20% with placebo). With diazoxide from 50 to 60 min coronary occlusion, however, there was marked hypotension, and infarct size (44% ± 7%) and area of no-reflow were not reduced (35% ± 25%).ConclusionsCardioprotection by diazoxide pretreatment was confirmed in adult pigs with reperfused acute myocardial infarction but is not feasible when diazoxide is administered in a more realistic scenario before reperfusion and causes hypotension. |
| first_indexed | 2024-04-09T17:19:45Z |
| format | Article |
| id | doaj.art-b2d4538d47d74f1099b721abc96e8c86 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T17:19:45Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-b2d4538d47d74f1099b721abc96e8c862023-04-19T04:44:15ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-04-011010.3389/fcvm.2023.11734621173462Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenarioPetra KleinbongardHelmut LiederAndreas SkyschallyGerd HeuschIntroductionDiazoxide is a powerful cardioprotective agent that activates mitochondrial ATP-dependent K-channels and stimulates mitochondrial respiration. Diazoxide reduced infarct size in isolated rodent heart preparations and upon pretreatment in juvenile pigs with coronary occlusion/reperfusion. We aimed to study the use of diazoxide in a more realistic adult pig model of reperfused acute myocardial infarction when diazoxide was administered just before reperfusion.Methods and resultsIn a first approach, we pretreated anaesthetised adult Göttingen minipigs with 7 mg kg−1 diazoxide (n = 5) or placebo (n = 5) intravenously over 10 min and subjected them to 60 min coronary occlusion and 180 min reperfusion; blood pressure was maintained by use of an aortic snare. The primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was the secondary endpoint. In a second approach, diazoxide (n = 5) was given from 50 to 60 min coronary occlusion, and blood pressure was not maintained. There was a significant reduction in infarct size (22% ± 11% of area at risk with diazoxide pretreatment vs. 47% ± 11% with placebo) and area of no-reflow (14% ± 14% of infarct size with diazoxide pretreatment vs. 46% ± 20% with placebo). With diazoxide from 50 to 60 min coronary occlusion, however, there was marked hypotension, and infarct size (44% ± 7%) and area of no-reflow were not reduced (35% ± 25%).ConclusionsCardioprotection by diazoxide pretreatment was confirmed in adult pigs with reperfused acute myocardial infarction but is not feasible when diazoxide is administered in a more realistic scenario before reperfusion and causes hypotension.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1173462/fullcardioprotectioncoronary microvascular obstructiondiazoxideinfarct sizemyocardial infarctionreperfusion |
| spellingShingle | Petra Kleinbongard Helmut Lieder Andreas Skyschally Gerd Heusch Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario Frontiers in Cardiovascular Medicine cardioprotection coronary microvascular obstruction diazoxide infarct size myocardial infarction reperfusion |
| title | Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario |
| title_full | Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario |
| title_fullStr | Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario |
| title_full_unstemmed | Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario |
| title_short | Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario |
| title_sort | diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario |
| topic | cardioprotection coronary microvascular obstruction diazoxide infarct size myocardial infarction reperfusion |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1173462/full |
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