Bauer R, Walter B, Gaser E, Rösel T, Kluge H, Zwiener U
Institute of Pathophysiology, Friedrich Schiller University, Jena, Germany.
Exp Toxicol Pathol. 1998 Sep;50(4-6):294-300. doi: 10.1016/S0940-2993(98)80009-2.
In order to clarify the influence of intrauterine growth restriction on systemic hemodynamics, catecholamine response, and regional distribution of brain energy metabolites per se and during mild hypoxic episodes a study was performed in thirty newborns with a well-characterized state of intrauterine and intra-natal development. Thirty animals were divided into fifteen normal weight piglets (NW) and fifteen intrauterine growth restricted (IUGR) piglets according to their birth weight. Category "NW" covered animals with a birth weight of > 40th percentile; IUGR category covered animals with a birth weight of > 5th and < 10th percentiles. Animals were anesthetized with halothane in 70% nitrous oxide and 30% oxygen and after immobilization artificially ventilated. The acid-base balance and blood gas values at baseline conditions were similar within the different groups investigated and consistent with other data obtained from anesthetized and artificially ventilated newborn piglets. Mild hypoxic hypoxia which was induced by lowering the FiO2 from 0.35 to 0.15 resulted in reduced arterial pO2 (NW: from 115 +/- 37 mmHg to 39 +/- 7 mmHg; IUGR: from 117 +/- 23 mmHg to 39 +/- 3 mmHg; p < 0.05), but arterial pH and pCO2 remained unchanged. Under baseline conditions arterial blood pressure, cardiac output, and myocardial contractility, expressed as dp/dt(max) and plasma catecholamine values were similar in all groups studied. Heart rate was slightly increased in IUGR (p < 0.05). Mild hypoxia led to a strong increase of myocardial contractility in NW as well as IUGR piglets to 2.4 and 2.7 fold and remained increased during recovery (p < 0.05). Moreover, total peripheral resistance was enhanced at the end of recovery period in IUGR animals (p < 0.05). There was a significant increase of epinephrine (E) in NW animals in comparison to sham-operated animals (p < 0.05). Interestingly, during reoxygenation the further increase in E and norepinephrine (NE) levels were enhanced in the animals which suffered from mild hypoxia (p < 0.05). Regional distribution of brain tissue metabolites was partly affected by intrauterine growth restriction. In particular, brain tissue glucose content was strongly reduced by 65 to 72 per cent in all brain regions investigated. Mild hypoxia led to an increase of about 30 percent in NW animals (p < 0.05). In IUGR piglets the percentage increase of brain glucose content was on an average more pronounced but with considerably higher variance. Also, a strong increase of brain lactate content appeared here (p < 0.05). In contrast, brain tissue ATP was quite similar in all groups studied, but brain creatine phosphate was significantly reduced in some forebrain structures of IUGR piglets after mild hypoxia (figure 2, p < 0.05). In summary, this investigation provides information on cardiovascular functions and brain metabolites of normal weight and naturally occurring growth restricted newborn piglets. Mild hypoxemia was well-tolerated from both animal groups. It is suggested that lactate may play a significant role as a source for brain energy production in the newborn IUGR piglets.
为了阐明宫内生长受限对全身血流动力学、儿茶酚胺反应以及脑能量代谢物本身及其在轻度缺氧发作期间区域分布的影响,我们对30例具有明确宫内和出生后发育状态的新生儿进行了一项研究。根据出生体重,将30只动物分为15只正常体重仔猪(NW)和15只宫内生长受限(IUGR)仔猪。“NW”组包括出生体重高于第40百分位数的动物;IUGR组包括出生体重高于第5百分位数且低于第10百分位数的动物。动物用氟烷在70%氧化亚氮和30%氧气中麻醉,固定后进行人工通气。在不同研究组中,基线条件下的酸碱平衡和血气值相似,与从麻醉和人工通气的新生仔猪获得的其他数据一致。通过将FiO2从0.35降至0.15诱导的轻度低氧性缺氧导致动脉pO2降低(NW组:从115±37 mmHg降至39±7 mmHg;IUGR组:从117±23 mmHg降至39±3 mmHg;p<0.05),但动脉pH和pCO2保持不变。在基线条件下,所有研究组的动脉血压、心输出量以及以dp/dt(max)表示的心肌收缩力和血浆儿茶酚胺值相似。IUGR组心率略有增加(p<0.05)。轻度缺氧导致NW组和IUGR组仔猪心肌收缩力强烈增加至2.4倍和2.7倍,并在恢复期间保持增加(p<0.05)。此外,IUGR组动物在恢复期结束时总外周阻力增强(p<0.05)。与假手术动物相比,NW组动物肾上腺素(E)显著增加(p<0.05)。有趣的是,在复氧期间,轻度缺氧动物的E和去甲肾上腺素(NE)水平进一步升高(p<0.05)。脑组织代谢物的区域分布部分受到宫内生长受限的影响。特别是,在所有研究的脑区中,脑组织葡萄糖含量强烈降低65%至72%。轻度缺氧导致NW组动物增加约30%(p<0.05)。在IUGR仔猪中,脑葡萄糖含量的增加百分比平均更明显,但方差更高。此外,此处脑乳酸含量也强烈增加(p<0.05)。相比之下,所有研究组的脑组织ATP相当相似,但轻度缺氧后,IUGR仔猪一些前脑结构中的脑磷酸肌酸显著降低(图2,p<0.05)。总之,本研究提供了正常体重和自然发生生长受限新生仔猪的心血管功能和脑代谢物的信息。两个动物组对轻度低氧血症耐受性良好。提示乳酸可能在新生IUGR仔猪脑能量产生中起重要作用。