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体外循环期间的常氧管理不会减少新生仔猪的脑线粒体功能障碍。

Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine.

机构信息

Division of Cardiothoracic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Resuscitation Science Center of Emphasis, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

出版信息

Int J Mol Sci. 2024 May 17;25(10):5466. doi: 10.3390/ijms25105466.

Abstract

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO was higher in hyperoxia animals throughout CPB ( < 0.001). There were no differences in cortical glycerol concentration between groups ( > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals ( < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration ( = 0.48), protein carbonyls ( = 0.74), or reactive oxygen species generation ( = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.

摘要

在儿科体外循环 (CPB) 期间,最佳的氧管理尚不清楚。我们之前使用高氧氧管理的方法,在 CPB 后显示皮质线粒体活性氧增加和线粒体功能下降。本研究旨在探讨 CPB 期间控制性氧合(正常氧合)是否可以减少皮质线粒体功能障碍和氧化损伤。10 头新生猪通过颈内插管在 34°C 下进行 3 小时的持续 CPB,流量> 100 mL/kg/min,目标动脉血氧分压 (PaO) 目标值<150 mmHg(正常氧合,n = 5)或>300 mmHg(高氧合,n = 5)。动物接受连续的血流动力学监测和连续的动脉血取样。皮质微透析液连续取样以定量甘油浓度(代表神经元损伤)和乳酸/丙酮酸比值(代表生物能功能障碍)。通过高分辨率呼吸测定法分析皮质组织以定量线粒体耗氧量和活性氧生成,以及皮质氧化蛋白羰基浓度以评估氧化损伤。CPB 期间,高氧组动物的血清 PaO 一直高于正常氧组(<0.001)。两组间皮质甘油浓度无差异(>0.2)。高氧组皮质乳酸/丙酮酸比值轻度升高(<0.03),但无临床意义(<30)。皮质线粒体呼吸(=0.48)、蛋白羰基(=0.74)或活性氧生成(=0.93)在两组间无差异。CPB 期间控制性氧合在急性情况下不会显著影响皮质线粒体功能或氧化损伤。需要进一步评估儿科 CPB 期间氧水平滴定对皮质组织和其他高危脑区的短期和长期影响,特别是在发绀存在的情况下。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f225/11122014/1def629bfdc1/ijms-25-05466-g001.jpg

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