Effect of global hypoxia-ischaemia followed by 24 h of mild hypothermia on organ pathology and biochemistry in a newborn pig survival model
Effect of global hypoxia-ischaemia followed by 24 h of mild hypothermia on organ pathology and biochemistry in a newborn pig survival model
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DOI：
10.1159/000067958
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发表时间：
2003-01-01
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影响因子：
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通讯作者：
Thoresen, M
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作者：
Satas, S;Loberg, E;Thoresen, M
背景：围产期窒息可能导致多器官损伤以及脑损伤。缺氧后低温（HT）可以保护除大脑之外的其他器官。本研究的目的是评估我们的全身缺氧缺血 (HI) 损伤的全身影响，并比较轻度 24 小时 HT 与常温 (NT) 在非镇静恢复期间的效果。方法：对 38 头新生猪进行 45 分钟的全身 HI，通过使用类似 6% O-2 的通气进行。在复氧时，猪被随机分配至 NT 或 HT。将18头NT仔猪在直肠温度39.0℃下维持72小时。将 23 头 HT 猪（20 头实验性 HT 和 3 头假对照）冷却至直肠温度 35°C，持续 24 小时，然后恢复 NT，然后动物又存活了 48 小时。结果：所有病灶均较小，无明显临床效果。心脏（6 HT vs. 9 NT）、肝脏（9 HT vs. 7 NT）、肾脏（6 HT vs. 9 NT）或肠道损伤（8 HT vs. 2 NT，p = 0.07）的发生率在两组中没有差异。更多 HT 仔猪出现肺损伤，其中 10 头为 HT，3 头为 NT。与基线值相比，HI 损伤后血浆 [Na]、[K]、[Ca] 和 [Mg] 显着增加。对于 24 小时期间，HT 组血浆 [K] 和 [Ca] 显着较高，平均曲线下面积 (AUC) 为 [K] AUC(HT) 4.4 mmol/l 对比 AUC(NT) 3.9 mmol/l，p = 0.04；[Ca] AUC(HT) 2.7 mmol/l 对比 AUC(NT) 2.5 mmol/l，p =分别为 0.01。天冬氨酸转氨酶在 HT 组中在 48 小时达到峰值，在 NT 组中在 24 小时达到峰值。 HT 猪的肌酐在 >72 小时达到峰值，NT 猪则在 48 小时达到峰值。 HT 猪的白细胞 (WBC) 在 12 小时达到峰值，NT 动物则在 6 小时达到峰值。 HT 猪在冷却过程中 WBC 的 AUC 显着较低（AUCHT 11.1 对比 AUC(NT) 15.3 10(3)/mm(3)，p = 0.04）。 HT 猪在 HT 的最后 12 小时内需要更多的葡萄糖来维持正常的血糖。 HT 动物在降温过程中也需要更多的氧气来维持 PaO2。结论：24 小时的轻度 HT 并没有减少任何器官的损伤。 HT 组的肺损伤略有增加。生化或病理变化均不具有临床意义。我们得出的结论是，与 NT 相比，24 小时轻度 HT 不会对器官系统产生不利影响。冷却过程中需要额外的葡萄糖和氧气以维持正常值。版权所有 (C) 2003 S. Karger AG，巴塞尔。
Background: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. Method: Thirty-eight newborn pigs were subjected to 45 min of global HI by ventilating them with similar to6% O-2. On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0degreesC for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35degreesC for 24 h before NT was resumed and the animals then survived a further 48 h. Results: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6 HT vs. 9 NT) or intestinal injury (8 HT vs. 2 NT, p = 0.07) was not different in the two groups. More HT piglets developed lung injury, 10 HT and 3 NT. Plasma [Na], [K], [Ca] and [Mg] increased significantly after the HI insult as compared to baseline values. For the 24-hour period plasma [K] and [Ca] were significantly higher in the HT group, the mean area under the curve (AUC) being for [K] AUC(HT) 4.4 mmol/l vs. AUC(NT) 3.9 mmol/l, p = 0.04 and for [Ca] AUC(HT) 2.7 mmol/l vs. AUC(NT) 2.5 mmol/l, p = 0.01, respectively. Aspartate aminotransferase peaked at 48 h in the HT group and at 24 h in the NT group. Creatinine peaked at >72 h in the HT pigs and at 48 h in the NT pigs. White blood cells (WBC) peaked at 12 h for the HT pigs and at 6 h for the NT animals. AUC of the WBC during the cooling was significantly lower in the HT pig (AUCHT 11.1 vs. AUC(NT) 15.3 10(3)/mm(3), p = 0.04). The HT pigs needed more glucose to maintain normal glucose during the last 12 h of HT. Also HT animals needed more oxygen during cooling to maintain PaO2. Conclusion: Twenty-four hours of mild HT did not reduce damage in any organ. There was a slight increase in lung damage in the HT group. None of the biochemical or pathological changes were of clinical significance. We conclude that mild HT for 24 h does not affect the organ systems adversely when compared to NT. Additional glucose and oxygen is needed during cooling to maintain normal values. Copyright (C) 2003 S. Karger AG, Basel.