Detrimental effects of nicotine and endotoxin in the newborn piglet brain during severe hypoxemia

被引:16
作者
Froen, JF [1 ]
Amerio, G
Stray-Pedersen, B
Saugstad, OD
机构
[1] Univ Oslo, Natl Hosp, Dept Pediat Res, N-0027 Oslo, Norway
[2] Univ Oslo, Natl Hosp, Dept Obstet & Gynecol, N-0027 Oslo, Norway
[3] Univ Oslo, Natl Hosp, Inst Surg Res, N-0027 Oslo, Norway
来源
BIOLOGY OF THE NEONATE | 2002年 / 82卷 / 03期
关键词
endotoxin; nicotine; hypoxemia; perinatal brain damage; brain;
D O I
10.1159/000063610
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Hypoxia-ischemia is a major cause of perinatal brain damage, but evidence shows that brain injury also is associated with intrauterine infections and maternal smoking. The mechanisms are not known, and we therefore explored the effects of experimental inflammation or nicotine on perinatal brain metabolism and injury during severe hypoxemia. Twenty-eight 1-week-old piglets were anesthetized and instrumented with microdialysis probes in the striatum and brainstem. We studied three pretreatment groups: (1) 20 mug/kg i.v. nicotine (n = 9); (2) 1 mug/kg i.v. endotoxin from Escherichia coli(n = 11), or (3) control (n = 8). The piglets were subsequently exposed to 30 min of hypoxemia (6% O-2). In order to minimize any ischemic component and increase survival, this was abrupted for 1 min if blood pressure fell to 30 mm Hg. During hypoxemia, both the pretreatment with endotoxin and nicotine induced higher levels of extracellular lactate and peak lactate/pyruvate ratio compared with controls (54.7 +/- 9.6 (p < 0.01) and 65.2 +/- 13.1 (p < 0.02) vs. 15.9 +/- 7.4, respectively), reflecting a deterioration of the metabolic status in these groups. The two pretreated groups reached significantly higher peak levels of extracellular glycerol (30.9 +/- 4.1 vs. 77.9 +/- 12.7 and 89.4 +/- 14.2 mumol/l, respectively, p = 0.01), indicating a higher level of cellular membrane disintegration or leakage. In addition, 3 endotoxin piglets and 4 nicotine piglets died during reoxygenation, while all controls survived (p 0.13 and p < 0.04, respectively). Mortality was associated with a rise in extracellular glutamate at the end of hypoxemia/start reoxygenation (p = 0.02). These findings contribute in explaining how nicotine and inflammatory response to bacterial toxins could act as cofactors for hypoxic-ischemic neurologic injury in the immature brain. Copyright (C) 2002 S. Karger AG, Basel.
引用
收藏
页码:188 / 196
页数:9
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