Department of Emergency Medicine, The Second Affiliated Hospital of Soochow University, Soochow, China.
Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, Virginia, USA.
Ther Hypothermia Temp Manag. 2020 Dec;10(4):192-203. doi: 10.1089/ther.2019.0038. Epub 2020 Jan 28.
The objective of this study was to investigate the effects of pharmacologically induced hypothermia with WIN55, 212-2 (WIN)on postresuscitation myocardial function, microcirculation, and metabolism-specific lipids in a rat cardiac arrest (CA) model. Ventricular fibrillation was electrically induced and untreated for 6 minutes in 24 Sprague-Dawley rats weighing 450-550 g. Cardiopulmonary resuscitation including chest compression and mechanical ventilation was then initiated and continued for 8 minutes, followed by defibrillation. At 5 minutes after restoration of spontaneous circulation (ROSC), animals were randomized into four groups: (1) normothermia with vehicle (NT); (2) physical hypothermia with vehicle (PH); (3) WIN55, 212-2 with normothermia (WN); and (4) WIN55, 212-2 with hypothermia (WH). For groups of WN and WH, WIN was administered by continuous intravenous infusion with a syringe pump for 4 hours. PH started at 5 minutes after resuscitation. NT maintained core temperature at 37°C ± 0.2°C with the aid of a heating blanket. Hypothermia groups maintained temperature at 33°C ± 0.5°C for 4 hours after ROSC. There was a significant improvement in myocardial function as measured by ejection fraction, cardiac output, and myocardial performance index in animals treated with WH and PH beginning at 1 hour after start of infusion. In the WH and PH groups, buccal microcirculation was significantly improved compared with NT and WN. Plasma at pre-CA and ROSC 4 hours was harvested for lipid metabolism. The WH group appeared to be closer to baseline than the other groups in lipid metabolism. lysophosphatidylcholine (LPC) 18:2, free fatty acid (FFA) 22:6, and ceramide (CER) (24:0) changed significantly among the lipidomic data compared with NT ( < 0.05). Postresuscitation hypothermia improved myocardial function and microcirculation. WH-mediated lipid metabolism had the best metabolic outcome to bring back the animals to normal metabolism, which may be protective to improve outcomes of CA. LPC 18:2, FFA 22:6, and CER (24:0) may be important predictors of outcomes of CA.
本研究旨在探讨 WIN55,212-2（WIN）诱导的低温对心脏骤停（CA）模型复苏后心肌功能、微循环和代谢特异性脂质的影响。24 只体重 450-550g 的 Sprague-Dawley 大鼠通过电诱导心室颤动，并在未经治疗的情况下持续 6 分钟。然后开始心肺复苏，包括胸外按压和机械通气，持续 8 分钟，随后进行除颤。在自主循环恢复（ROSC）后 5 分钟，动物随机分为四组：（1）常温下用载体（NT）；（2）常温下用物理降温（PH）；（3）WIN55,212-2 加常温（WN）；（4）WIN55,212-2 加低温（WH）。WN 和 WH 组通过注射器泵持续静脉输注 WIN 4 小时。PH 于复苏后 5 分钟开始。NT 通过加热毯将核心温度维持在 37°C±0.2°C。WH 组在 ROSC 后 4 小时内将温度维持在 33°C±0.5°C。从开始输注后 1 小时开始，WH 和 PH 治疗的动物心肌功能得到显著改善，表现为射血分数、心输出量和心肌做功指数。在 WH 和 PH 组中，与 NT 和 WN 相比，颊部微循环明显改善。在 CA 前和 ROSC 4 小时采集血浆进行脂质代谢。与其他组相比，WH 组的脂质代谢更接近基线。溶血磷脂酰胆碱（LPC）18:2、游离脂肪酸（FFA）22:6 和神经酰胺（CER）（24:0）与 NT 相比，脂质组学数据中的脂质代谢发生显著变化（<0.05）。再灌注后低温可改善心肌功能和微循环。WH 介导的脂质代谢具有最佳的代谢结果，可使动物恢复正常代谢，这可能有助于改善 CA 的预后。LPC 18:2、FFA 22:6 和 CER（24:0）可能是 CA 结局的重要预测因子。
