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先天性心脏病患儿在体外循环下心肺转流术中的活性氧代脂质。

Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass.

机构信息

Department of Critical Care Medicine, UPMC and University of Pittsburgh, Pittsburgh, PA.

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA.

出版信息

Pediatr Crit Care Med. 2020 Jan;21(1):33-41. doi: 10.1097/PCC.0000000000002036.

Abstract

OBJECTIVES

To determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration).

DESIGN

Prospective observational study.

SETTING

Twelve-bed cardiac ICU in a university-affiliated children's hospital.

PATIENTS

Children were prospectively enrolled during their preoperative clinic appointments with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass INTERVENTIONS:: None.

MEASUREMENTS AND MAIN RESULTS

Plasma was collected at the start and end of cardiopulmonary bypass in 34 patients. 9-hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, plasma hemoglobin, and WBC increased. 9:13-hydroxyoctadecadienoic acid at the start of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours postcardiopulmonary bypass (R = 0.25; p < 0.01), milrinone use (R = 0.17; p < 0.05), and WBC (R = 0.12; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the end of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours (R = 0.17; p < 0.05), 24-48 hours postcardiopulmonary bypass (R = 0.12; p < 0.05), and milrinone use (R = 0.19; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the start and end of cardiopulmonary bypass were associated with the changes in plasma hemoglobin (R = 0.21 and R = 0.23; p < 0.01). The changes in plasma hemoglobin was associated with milrinone use (R = 0.36; p < 0.001) and vasoactive-inotropic score less than 2 hours (R = 0.22; p < 0.01), 2-24 hours (R = 0.24; p < 0.01), and 24-48 hours (R = 0.48; p < 0.001) postcardiopulmonary bypass. Cardiopulmonary bypass duration, 9:13-hydroxyoctadecadienoic acid at start of cardiopulmonary bypass, and plasma hemoglobin may be risk factors for high vasoactive-inotropic score. Cardiopulmonary bypass duration, changes in plasma hemoglobin, 9:13-hydroxyoctadecadienoic acid, and vasoactive-inotropic score correlate with ICU and hospital length of stay and/mechanical ventilation days.

CONCLUSIONS

In low-risk pediatric patients undergoing cardiopulmonary bypass, 9:13-hydroxyoctadecadienoic acid was associated with changes in plasma hemoglobin, vasoactive-inotropic score, and WBC count, and may be a risk factor for high vasoactive-inotropic score, indicating possible inflammatory and vasoactive effects. Further studies are warranted to delineate the role of hydroxyoctadecadienoic acids and plasma hemoglobin in cardiopulmonary bypass-related dysfunction and to explore hydroxyoctadecadienoic acid production as a potential therapeutic target.

摘要

目的

确定在接受心脏手术的婴儿和儿童进行心肺转流期间产生的 9-羟基十八碳二烯酸和 13-羟基十八碳二烯酸,评估它们与细胞游离血浆血红蛋白增加的关系,通过炎症和血管活性标志物(白细胞计数、米力农使用、血管活性-正性肌力评分)提供生物活性的证据,并检查它们与整体临床负担(重症监护室/医院住院时间和机械通气持续时间)的关系。

设计

前瞻性观察性研究。

设置

大学附属儿童医院的 12 床心脏重症监护病房。

患者

在术前就诊时,前瞻性纳入符合以下标准的儿童:年龄大于 1 个月至小于 18 岁,需要心肺转流的手术。

干预措施

无。

测量和主要结果

34 例患者在心肺转流开始和结束时采集血浆。9-羟基十八碳二烯酸、13-羟基十八碳二烯酸、血浆血红蛋白和白细胞计数增加。心肺转流开始时的 9:13-羟基十八碳二烯酸与心肺转流后 2-24 小时的血管活性-正性肌力评分(R = 0.25;p < 0.01)、米力农使用(R = 0.17;p < 0.05)和白细胞计数(R = 0.12;p < 0.05)相关。心肺转流结束时的 9:13-羟基十八碳二烯酸与心肺转流后 2-24 小时(R = 0.17;p < 0.05)、24-48 小时(R = 0.12;p < 0.05)和米力农使用(R = 0.19;p < 0.05)相关。心肺转流开始和结束时的 9:13-羟基十八碳二烯酸与血浆血红蛋白的变化相关(R = 0.21 和 R = 0.23;p < 0.01)。血浆血红蛋白的变化与米力农使用(R = 0.36;p < 0.001)和心肺转流后小于 2 小时的血管活性-正性肌力评分(R = 0.22;p < 0.01)、2-24 小时(R = 0.24;p < 0.01)和 24-48 小时(R = 0.48;p < 0.001)相关。心肺转流时间、心肺转流开始时的 9:13-羟基十八碳二烯酸和血浆血红蛋白可能是血管活性-正性肌力评分高的危险因素。心肺转流时间、血浆血红蛋白变化、9:13-羟基十八碳二烯酸和血管活性-正性肌力评分与 ICU 和医院住院时间和/或机械通气天数相关。

结论

在接受心肺转流的低风险儿科患者中,9:13-羟基十八碳二烯酸与血浆血红蛋白、血管活性-正性肌力评分和白细胞计数的变化相关,可能是血管活性-正性肌力评分高的危险因素,表明可能存在炎症和血管活性作用。需要进一步研究来阐明羟基十八碳二烯酸和血浆血红蛋白在心肺转流相关功能障碍中的作用,并探索羟基十八碳二烯酸的产生作为潜在的治疗靶点。

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