Protocol for the MicroRESUS study: The impact of circulatory shock and resuscitation on microcirculatory function and mitochondrial respiration after cardiovascular surgery.

Protocol for the MicroRESUS study: The impact of circulatory shock and resuscitation on microcirculatory function and mitochondrial respiration after cardiovascular surgery.
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DOI:
10.1371/journal.pone.0273349
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
文献类型:
--
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尽管目前的复苏策略,心脏手术后循环休克和器官损伤发生在25-40%的患者。心脏手术后的目标导向复苏引起了极大的兴趣,但临床实践正常化血流动力学变量,包括平均动脉压、心脏充盈压和心输出量,可能无法逆转微循环异常,也无法解决细胞缺氧问题。最近的技术进步使得测量活体人体组织和血细胞中的氧气输送和氧气利用系统的关键成分成为可能。MicroRESUS研究将是首个测量循环休克患者微循环和线粒体功能的研究,并将这些发现与临床结果联系起来。这将是一项前瞻性观察性研究,包括接受选择性心血管手术合并体外循环(CPB)的患者。将用舌下入射暗场视频显微镜定量微循环。线粒体呼吸将通过底物-解偶联剂-抑制剂滴定法和高分辨率呼吸计在复苏和恢复期间的基线和连续时间点对外周血单个核细胞进行测量,作为可能的液体生物标志物。血浆样本将保存下来,以供将来分析内皮损伤和微循环功能障碍的其他机制。将测量30天无呼吸机和无血管加压剂天数(VVFDs)作为主要结局,同时测量顺序器官衰竭评估评分和其他临床参数,以确定与传统复苏目标相比,微循环和线粒体呼吸的变化是否与临床结局有更强的相关性。这将是首个对行心脏搭桥术的人类循环休克患者的微循环和线粒体功能进行检查的前瞻性研究,并解决心血管文献中一个关键的机制知识空白。这项研究的结果将指导未来的研究工作和治疗休克患者的发展。
Despite current resuscitation strategies, circulatory shock and organ injury after cardiac surgery occur in 25–40% of patients. Goal-directed resuscitation after cardiac surgery has generated significant interest, but clinical practice to normalize hemodynamic variables including mean arterial pressure, cardiac filling pressures, and cardiac output may not reverse microcirculation abnormalities and do not address cellular dysoxia. Recent advances in technology have made it possible to measure critical components of oxygen delivery and oxygen utilization systems in live human tissues and blood cells. The MicroRESUS study will be the first study to measure microcirculatory and mitochondrial function in patients with circulatory shock and link these findings with clinical outcomes. This will be a prospective, observational study that includes patients undergoing elective cardiovascular surgery with cardiopulmonary bypass (CPB). Microcirculation will be quantified with sublingual incident dark field videomicroscopy. Mitochondrial respiration will be measured by performing a substrate–uncoupler–inhibitor titration protocol with high resolution respirometry on peripheral blood mononuclear cells at baseline and serial timepoints during resuscitation and at recovery as a possible liquid biomarker. Plasma samples will be preserved for future analysis to examine endothelial injury and other mechanisms of microcirculatory dysfunction. Thirty-day ventilator and vasopressor-free days (VVFDs) will be measured as a primary outcome, along with sequential organ failure assessment scores, and other clinical parameters to determine if changes in microcirculation and mitochondrial respiration are more strongly associated with clinical outcomes compared to traditional resuscitation targets. This will be the first prospective study to examine both microcirculatory and mitochondrial function in human patients with circulatory shock undergoing cardiac bypass and address a key mechanistic knowledge gap in the cardiovascular literature. The results of this study will direct future research efforts and therapeutic development for patients with shock.
血液单核细胞的线粒体呼吸功能障碍与早期心力衰竭患者的心脏功能障碍有关
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