An acute estrogen receptor agonist enhances protective effects of cardioplegia in hearts from aging male and female mice.,Experimental Gerontology

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An acute estrogen receptor agonist enhances protective effects of cardioplegia in hearts from aging male and female mice.
Experimental Gerontology ( IF 3.3 ) Pub Date : 2020-09-17 , DOI: 10.1016/j.exger.2020.111093
Anjali Ghimire ₁ , Susan E Howlett ₂

Affiliation

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.

中文翻译：

急性雌激素受体激动剂可增强雄性和雌性小鼠心脏停搏的保护作用。

背景

G蛋白偶联雌激素受体（GPER）介导对雌激素的快速反应。尽管尚不清楚GPER的激活是否有助于老化心肌，但GPER的激活可能有助于雌激素在缺血和再灌注中的心脏保护作用。我们确定了将GPER激动剂（G1）添加到标准心脏停搏液中（用于保护心脏免受心脏手术期间的缺血再灌注损伤的影响）是否会改善成年和成年小鼠的性别。

方法

用Krebs-Henseleit缓冲液灌注成年（6–9 mos）和年长（22–28 mos）小鼠的心脏15分钟（37°C），然后冷（6–7°C）St. Thomas'2心麻痹用G1（0.5μM），G1（0.5μM）加G15（GPER拮抗剂; 1μM）或赋形剂处理6分钟。然后使心脏经受整体缺血（90分钟； 23–24°C）和再灌注（30分钟； 37°C）。用氯化三苯四唑定量梗塞面积。

结果

在成年女性中，在再灌注时，对照心脏的左心室发育压力（LVDP）仅恢复到基线的45.1±11.9％，但是在G1治疗下恢复到76.5±3.9％（p <0.05），这被G15阻断。在老年男性和女性中也获得了类似的结果（老年男性和女性分别为LVDP = 51.5±10.6％与84.8±8.7％和51.9±5.5％与90.0±6.1％； p <0.05）。相比之下，G1对成年男性心脏中LVDP的恢复没有影响（26.6±8.9％对46.0±14.2％）。压力发展和衰减的速率在再灌注中显示出相似的恢复模式。尽管G1对成年雄性小鼠的梗死面积无影响，但G1处理的所有年龄较大的小鼠和年轻雌性小鼠的心脏梗死明显较小（对照组为48.1±7.7％，而G1为32.6±8.0％）。