Acute postischemic treatment with estrogen receptor-α agonist or estrogen receptor-β agonist improves myocardial recovery

Nicholas D. Vornehm, Meijing Wang, Aaron Abarbanell, Jeremy Herrmann, Brent Weil, Jiangjing Tan, Yue Wang, Megan Kelly, Daniel R. Meldrum

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background: After ischemia/reperfusion (I/R) injury, female hearts demonstrate improved functional recovery compared with male, which suggests a protective role for estrogen. Acute postischemic treatment with 17-β-estradiol (E2) attenuates myocardial dysfunction. However, it is unknown by which estrogen receptor (ER) E2 mediates this acute cardioprotection during I/R. Therefore, we hypothesize that postischemic infusion of the selective ER-α agonist (4,4',4''-[4-propyl-(1H)-pyrazole-1,3,5-triyl]tris-phenol [PPT]) or the selective ER-β agonist (2,3-bis(4-hydroxyphenyl)-propionitrile [DPN]) will improve myocardial function after I/R injury. Methods: Isolated, perfused hearts (Langendorff) from adult male rats were subjected to 25 minutes of ischemia followed by 40 minutes of reperfusion. Hearts (n = 4-6 per group) were randomly infused with either perfusate, PPT or DPN at 1, 10, or 100 nmol/L throughout reperfusion. After I/R, heart tissue was analyzed for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, vascular endothelial growth factor (VEGF), and lactate dehydrogenase (LDH). Results: Postischemic treatment with 10 nmol/L of PPT significantly improved myocardial function. Additionally, 10 or 100 nmol/L of DPN significantly increased myocardial functional recovery after I/R injury, with maximum benefit at the 10 nmol/L dose. A trend toward lower levels of LDH was noted in DPN- and PPT-treated groups after I/R injury. Neither PPT nor DPN affected myocardial production of TNF-α or IL-1β. However, higher levels of myocardial VEGF were noted in the PPT-treated group compared with controls. Conclusion: Both ER-α and ER-β are involved in mediating E2-induced rapid cardioprotection after I/R injury. Advancing our understanding of both ER subtypes may be useful for the development of novel strategies that may benefit both males and females in response to myocardial ischemia.

Original languageEnglish (US)
Pages (from-to)145-154
Number of pages10
JournalSurgery
Volume146
Issue number2
DOIs
StatePublished - Aug 1 2009

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ASJC Scopus subject areas

  • Surgery

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