An acute estrogen receptor agonist enhances protective effects of cardioplegia in hearts from aging male and female mice.
Cardiac surgery
Cardioplegia
Cardioprotection
G-protein estrogen receptor agonist
Ischemia-reperfusion injury
Langendorff perfusion
Journal
Experimental gerontology
ISSN: 1873-6815
Titre abrégé: Exp Gerontol
Pays: England
ID NLM: 0047061
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
27
05
2020
revised:
08
09
2020
accepted:
11
09
2020
pubmed:
21
9
2020
medline:
28
4
2021
entrez:
20
9
2020
Statut:
ppublish
Résumé
The G-protein coupled estrogen receptor (GPER) mediates rapid responses to estrogen. GPER activation may contribute to cardioprotective effects of estrogen in ischemia and reperfusion, although whether it is beneficial in aging myocardium is unclear. We determined whether a GPER agonist (G1) added to standard cardioplegic solution (used to protect hearts from ischemia-reperfusion injury during cardiac surgery) would improve outcomes in isolated hearts from adult and aged mice of both sexes. Hearts from young adult (6-9 mos) and older (22-28 mos) mice were perfused with Krebs-Henseleit buffer for 15 min (37 °C) followed by cold (6-7 °C) St. Thomas'2 cardioplegia with G1 (0.5 μM), G1 (0.5 μM) plus G15 (GPER antagonist; 1 μM) or vehicle for 6 min. Hearts were then subjected to global ischemia (90 min; 23-24 °C) and reperfusion (30 min; 37 °C). Infarct size was quantified with triphenyltetrazolium chloride. In adult females, left ventricular developed pressure (LVDP) recovered to only 45.1 ± 11.9% of baseline in control hearts in reperfusion, but recovered to 76.5 ± 3.9% with G1 treatment (p < 0.05) and this was blocked by G15. Similar results were obtained in older males and females (LVDP = 51.5 ± 10.6% vs. 84.8 ± 8.7% and 51.9 ± 5.5% vs. 90.0 ± 6.1% for older males and females, respectively; p < 0.05). By contrast, G1 had no effect on recovery of LVDP in hearts from adult males (26.6 ± 8.9% vs. 46.0 ± 14.2%). The rates of pressure development and decay showed a similar pattern of recovery in reperfusion. Infarcts were significantly smaller in G1-treated hearts from all older mice and in younger females, although G1 had no impact on infarct size in adult males (48.1 ± 7.7% for control vs. 32.6 ± 8.0% for G1). G1 enhances cardioprotective properties of a standard cardioplegic solution in the aging myocardium of both sexes. Supplementation of cardioplegic solutions with GPER agonists is a potential translational intervention that may improve cardiac surgery outcomes in older adults.
Sections du résumé
BACKGROUND
The G-protein coupled estrogen receptor (GPER) mediates rapid responses to estrogen. GPER activation may contribute to cardioprotective effects of estrogen in ischemia and reperfusion, although whether it is beneficial in aging myocardium is unclear. We determined whether a GPER agonist (G1) added to standard cardioplegic solution (used to protect hearts from ischemia-reperfusion injury during cardiac surgery) would improve outcomes in isolated hearts from adult and aged mice of both sexes.
METHODS
Hearts from young adult (6-9 mos) and older (22-28 mos) mice were perfused with Krebs-Henseleit buffer for 15 min (37 °C) followed by cold (6-7 °C) St. Thomas'2 cardioplegia with G1 (0.5 μM), G1 (0.5 μM) plus G15 (GPER antagonist; 1 μM) or vehicle for 6 min. Hearts were then subjected to global ischemia (90 min; 23-24 °C) and reperfusion (30 min; 37 °C). Infarct size was quantified with triphenyltetrazolium chloride.
RESULTS
In adult females, left ventricular developed pressure (LVDP) recovered to only 45.1 ± 11.9% of baseline in control hearts in reperfusion, but recovered to 76.5 ± 3.9% with G1 treatment (p < 0.05) and this was blocked by G15. Similar results were obtained in older males and females (LVDP = 51.5 ± 10.6% vs. 84.8 ± 8.7% and 51.9 ± 5.5% vs. 90.0 ± 6.1% for older males and females, respectively; p < 0.05). By contrast, G1 had no effect on recovery of LVDP in hearts from adult males (26.6 ± 8.9% vs. 46.0 ± 14.2%). The rates of pressure development and decay showed a similar pattern of recovery in reperfusion. Infarcts were significantly smaller in G1-treated hearts from all older mice and in younger females, although G1 had no impact on infarct size in adult males (48.1 ± 7.7% for control vs. 32.6 ± 8.0% for G1).
CONCLUSION
G1 enhances cardioprotective properties of a standard cardioplegic solution in the aging myocardium of both sexes. Supplementation of cardioplegic solutions with GPER agonists is a potential translational intervention that may improve cardiac surgery outcomes in older adults.
Identifiants
pubmed: 32950614
pii: S0531-5565(20)30441-1
doi: 10.1016/j.exger.2020.111093
pii:
doi:
Substances chimiques
Cardioplegic Solutions
0
Estrogens
0
Receptors, Estrogen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111093Subventions
Organisme : CIHR
ID : PGT 155961
Pays : Canada
Organisme : CIHR
ID : MOP 97973
Pays : Canada
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.