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深低温停循环后低流量体外循环对新生仔猪脑代谢的影响:pH -stat 和 α-stat 管理的比较。

Effect of deep hypothermic circulatory arrest followed by low-flow cardiopulmonary bypass on brain metabolism in newborn piglets: comparison of pH-stat and α-stat management.

机构信息

Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

出版信息

Pediatr Crit Care Med. 2011 Mar;12(2):e79-86. doi: 10.1097/PCC.0b013e3181e89e91.

DOI:10.1097/PCC.0b013e3181e89e91
PMID:20601925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2951487/
Abstract

OBJECTIVE

To compare the effects of pH-stat and α-stat management before deep hypothermic circulatory arrest followed by a period of low-flow (two rates) cardiopulmonary bypass on cortical oxygenation and selected regulatory proteins: Bax, Bcl-2, Caspase-3, and phospho-Akt.

DESIGN

Piglets were placed on cardiopulmonary bypass, cooled with pH-stat or α-stat management to 18 °C over 30 mins, subjected to 30-min deep hypothermic circulatory arrest and 1-hr low flow at 20 mL/kg/min (LF-20) or 50 mL/kg/min (LF-50), rewarmed to 37 °C, separated from cardiopulmonary bypass, and recovered for 6 hrs.

SUBJECTS

Newborn piglets, 2-5 days old, assigned randomly to experimental groups.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Cortical oxygen was measured by oxygen-dependent quenching of phosphorescence; proteins were measured by Western blots. The means from six experiments ± sem are presented as % of α-stat. Significance was determined by Student's t test. For LF-20, cortical oxygenation was similar for α-stat and pH-stat, whereas for LF-50, it was significantly better using pH-stat. For LF-20, the measured proteins were not different except for Bax in the cortex (214 ± 24%, p = .006) and hippocampus (118 ± 6%, p = .024) and Caspase 3 in striatum (126% ± 7%, p = .019). For LF-50, in pH-stat group: In cortex, Bax and Caspase-3 were lower (72 ± 8%, p = .001 and 72 ± 10%, p = .004, respectively) and pAkt was higher (138 ± 12%, p = .049). In hippocampus, Bcl-2 and Bax were not different but pAkt was higher (212 ± 37%, p = .005) and Caspase 3 was lower (84 ± 4%, p = .018). In striatum, Bax and pAkt did not differ, but Bcl-2 increased (146 ± 11%, p = .001) and Caspase-3 decreased (81 ± 11%, p = .042).

CONCLUSIONS

In this deep hypothermic circulatory arrest-LF model, when flow was 20 mL/kg/min, there was little difference between α-stat and pH-stat management. However, for LF-50, pH-stat management resulted in better cortical oxygenation during recovery and Bax, Bcl-2, pAk, and Caspase-3 changes were consistent with lesser activation of proapoptotic signaling with pH-stat than with α-stat.

摘要

目的

比较深低温停循环前 pH -stat 和 α-stat 管理与低流量(两种流速)心肺转流后皮质氧合和选定的调节蛋白的影响:Bax、Bcl-2、Caspase-3 和磷酸化 Akt。

设计

小猪置于心肺转流上,用 pH-stat 或 α-stat 管理冷却至 18°C 30 分钟,深低温停循环 30 分钟,低流量 20 毫升/公斤/分钟(LF-20)或 50 毫升/公斤/分钟(LF-50)1 小时,复温至 37°C,与心肺转流分离并恢复 6 小时。

对象

新生小猪,2-5 天大,随机分配到实验组。

干预措施

无。

测量和主要结果

皮质氧通过磷光的氧依赖性猝灭来测量;蛋白质通过 Western blot 测量。结果以六次实验的平均值±sem 表示为 α-stat 的%。通过学生 t 检验确定显著性。对于 LF-20,α-stat 和 pH-stat 的皮质氧合相似,而对于 LF-50,使用 pH-stat 则明显更好。对于 LF-20,除皮质(214±24%,p=0.006)和海马(118±6%,p=0.024)中的 Bax 和纹状体中的 Caspase 3 外,其他测量的蛋白质没有差异(126%±7%,p=0.019)。对于 LF-50,在 pH-stat 组中:皮质中,Bax 和 Caspase-3 降低(72±8%,p=0.001 和 72±10%,p=0.004),pAkt 升高(138±12%,p=0.049)。海马中,Bcl-2 和 Bax 没有差异,但 pAkt 升高(212±37%,p=0.005),Caspase 3 降低(84±4%,p=0.018)。纹状体中,Bax 和 pAkt 没有差异,但 Bcl-2 增加(146±11%,p=0.001),Caspase 3 减少(81±11%,p=0.042)。

结论

在这种深低温停循环-LF 模型中,当流量为 20 毫升/公斤/分钟时,α-stat 和 pH-stat 管理之间几乎没有差异。然而,对于 LF-50,pH-stat 管理在恢复期间导致皮质氧合更好,Bax、Bcl-2、pAk 和 Caspase-3 的变化与 pH-stat 比 α-stat 更能减少促凋亡信号的激活一致。

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Eur J Cardiothorac Surg. 2009 Apr;35(4):577-81; discussion 581. doi: 10.1016/j.ejcts.2009.01.001. Epub 2009 Feb 13.
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Response of brain oxygenation and metabolism to deep hypothermic circulatory arrest in newborn piglets: comparison of pH-stat and alpha-stat strategies.新生仔猪脑氧合与代谢对深低温停循环的反应:pH 稳态与α稳态策略的比较
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The effect of hypocapnia (PaCO2 27 mmHg) on CaM kinase IV activity, Bax/Bcl-2 protein expression and DNA fragmentation in the cerebral cortex of newborn piglets.低碳酸血症(动脉血二氧化碳分压27 mmHg)对新生仔猪大脑皮质中钙调蛋白激酶IV活性、Bax/Bcl-2蛋白表达及DNA片段化的影响。
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