Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: a comparison with therapeutic hypothermia.
Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: a comparison with therapeutic hypothermia.
复制标题
脂质乳液迅速恢复了惊人的小鼠心肌细胞的收缩力:与治疗性低温的比较。
DOI:
10.1097/ccm.0000000000000656
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发表时间:
2014-12
影响因子:
8.8
通讯作者:
Vanden Hoek TL
中科院分区:
文献类型:
--
作者:
Li J;Fettiplace M;Chen SJ;Steinhorn B;Shao Z;Zhu X;Li C;Harty S;Weinberg G;Vanden Hoek TL
Cooling following cardiac arrest can improve survival significantly. However, delays in achieving target temperature may decrease the overall benefits of cooling. Here we test whether lipid emulsion, a clinically approved drug reported to exert cardioprotection, can rescue heart contractility in the setting of delayed cooling in stunned mouse cardiomyocytes. Cell culture study Academic research laboratory Cardiomyocytes isolated from 1–2-day old C57BL6 mice Cardiomyocytes were exposed to 30 minutes of ischemia followed by 90 minutes reperfusion and 10 minutes isoproterenol with nine interventions: 1) no additional treatment; 2) intra-ischemic cooling at 32°C initiated 10 min prior to reperfusion; 3) delayed cooling started 20 minutes after reperfusion; 4) lipid emulsion + delayed cooling; 5) lipid emulsion (0.25%) administered at reperfusion; 6) lipid emulsion + intra-ischemic cooling; 7) delayed lipid emulsion; 8) lipid emulsion + delayed cooling + Akt inhibitor (API-2, 10 μM) and 9) lipid emulsion + delayed cooling + Erk inhibitor (U0126, 10 μM). Inhibitors were given to cells 1 h prior to ischemia. Contractility was recorded by real-time phase-contrast imaging and analyzed with pulse image velocimetry in MATLAB. Ischemia diminished cell contraction. The cardioprotective effect of cooling was diminished when delayed but was rescued by lipid emulsion. Further, lipid emulsion on its own improved recovery of the contractility to an equal extent as intra-ischemic cooling. However, co-treatment of lipid emulsion and intra-ischemic cooling did not further improve the recovery compared to either treatment alone. Moreover, Akt and Erk inhibitors blocked lipid emulsion-induced protection. Lipid emulsion improved contractility and rescued contractility in the context of delayed cooling. This protective effect required Akt and Erk signaling. Lipid emulsion might serve as a treatment or adjunct to cooling in ameliorating myocardial ischemia/reperfusion injury.