Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, Pa; Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa.
J Thorac Cardiovasc Surg. 2022 Jan;163(1):e47-e58. doi: 10.1016/j.jtcvs.2020.12.005. Epub 2020 Dec 11.
We aimed to determine the effects of selective antegrade cerebral perfusion compared with other perfusion strategies on indices of cerebral blood flow, oxygenation, cellular stress, and mitochondrial function.
One-week-old piglets (n = 41) were assigned to 5 treatment groups. Thirty-eight were placed on cardiopulmonary bypass. Of these, 30 were cooled to 18°C and underwent deep hypothermic circulatory arrest (n = 10), underwent selective antegrade cerebral perfusion at 10 mL/kg/min (n = 10), or remained on continuous cardiopulmonary bypass (deep hypothermic cardiopulmonary bypass, n = 10) for 40 minutes. Other subjects remained on normothermic cardiopulmonary bypass (n = 8) or underwent sham surgery (n = 3). Novel, noninvasive optical measurements recorded cerebral blood flow, cerebral tissue oxyhemoglobin concentration, oxygen extraction fraction, total hemoglobin concentration, and cerebral metabolic rate of oxygen. Invasive measurements of cerebral microdialysis and cerebral blood flow were recorded. Cerebral mitochondrial respiration and reactive oxygen species generation were assessed after the piglets were killed.
During hypothermia, deep hypothermic circulatory arrest piglets experienced increases in oxygen extraction fraction (P < .001), indicating inadequate matching of oxygen supply and demand. Deep hypothermic cardiopulmonary bypass had higher cerebral blood flow (P = .046), oxyhemoglobin concentration (P = .019), and total hemoglobin concentration (P = .070) than selective antegrade cerebral perfusion, indicating greater oxygen delivery. Deep hypothermic circulatory arrest demonstrated worse mitochondrial function (P < .05), increased reactive oxygen species generation (P < .01), and increased markers of cellular stress (P < .01). Reactive oxygen species generation was increased in deep hypothermic cardiopulmonary bypass compared with selective antegrade cerebral perfusion (P < .05), but without significant microdialysis evidence of cerebral cellular stress.
Selective antegrade cerebral perfusion meets cerebral metabolic demand and mitigates cerebral mitochondrial reactive oxygen species generation. Excess oxygen delivery during deep hypothermia may have deleterious effects on cerebral mitochondria that may contribute to adverse neurologic outcomes. We describe noninvasive measurements that may help guide perfusion strategies.
本研究旨在确定与其他灌注策略相比，选择性顺行性脑灌注对脑血流、氧合、细胞应激和线粒体功能等指标的影响。
选择一周龄的小猪（n=41）分为 5 个治疗组。其中 38 只小猪接受心肺转流术。其中，30 只小猪被冷却至 18°C，并接受深度低温停循环（n=10）、10ml/kg/min 的选择性顺行性脑灌注（n=10）或持续心肺转流（深低温心肺转流，n=10）40 分钟。其他对象保持在常温心肺转流（n=8）或进行假手术（n=3）。新型非侵入性光学测量记录脑血流、脑组织氧合血红蛋白浓度、氧摄取分数、总血红蛋白浓度和脑氧代谢率。记录有创性脑微透析和脑血流测量。小猪死后评估脑线粒体呼吸和活性氧生成。
在低温期间，深度低温停循环的小猪的氧摄取分数增加（P<0.001），表明氧供与氧需不匹配。深低温心肺转流的脑血流（P=0.046）、氧合血红蛋白浓度（P=0.019）和总血红蛋白浓度（P=0.070）均高于选择性顺行性脑灌注，表明氧输送更多。深度低温停循环显示出更差的线粒体功能（P<0.05）、增加的活性氧生成（P<0.01）和增加的细胞应激标志物（P<0.01）。与选择性顺行性脑灌注相比，深低温心肺转流的活性氧生成增加（P<0.05），但脑细胞应激的微透析证据无显著差异。
选择性顺行性脑灌注满足脑代谢需求，并减轻脑线粒体活性氧生成。深低温期间过多的氧输送可能对脑线粒体产生有害影响，从而导致不良的神经学结局。我们描述了可能有助于指导灌注策略的非侵入性测量。
