Coyle M G, Oh W, Stonestreet B S
Department of Pediatrics, Brown University School of Medicine, Women and Infants' Hospital of Rhode Island, Providence 02905.
Am J Physiol. 1993 Jan;264(1 Pt 2):H141-9. doi: 10.1152/ajpheart.1993.264.1.H141.
We tested the hypotheses that in newborn piglets indomethacin (Indo) pretreatment blunts the hyperemic brain blood flow (BF) and alters the cerebral metabolic responses to hypoxia and that these responses are dose dependent. We studied 23 chronically instrumented piglets exposed to graded hypoxia (O2 content: 7.1-0.4 microM O2/ml) after pretreatment with high (5 mg/kg, n = 8)-or low (0.3 mg/kg, n = 6)-dose Indo or placebo (diluent, n = 9). Total and regional brain BF increased significantly with decreasing O2 content values (P < 0.01) in all three groups. However, the rise in the brain BF curves with decreasing O2 content values was significantly (P < 0.05) lower in the high-compared with the low-dose group in all brain regions with the greatest effect in the caudal regions. Furthermore, the BF curves in the placebo-treated animals were similar to the low-dose group. The cerebral metabolic rate of O2 (CMR(O2)) and glucose metabolism were preserved in the three groups over all hypoxic ranges until severe hypoxia (O2 content < or = 1.1 microM O2/ml) was achieved in the high-dose group, when CMR(O2) decreased (P < 0.05), and glucose metabolism increased (P < 0.05). The mean arterial blood pressure in the high-dose group during severe hypoxia was 45 mmHg (P > 0.05). Although coupling of cerebral BF and CMR(O2) was preserved in the three groups, this association was significantly altered with high-dose pretreatment. We conclude that an attenuation in the hypoxia-induced brain perfusion by Indo is dose dependent. Alterations in CMR(O2) and glucose metabolism are observed with high-dose pretreatment during severe hypoxia, and the responses to hypoxia are similar with placebo and low-dose Indo pretreatment.
在新生仔猪中，吲哚美辛（Indo）预处理可减弱充血性脑血流量（BF），并改变大脑对缺氧的代谢反应，且这些反应具有剂量依赖性。我们研究了23只长期植入仪器的仔猪，在给予高剂量（5mg/kg，n = 8）或低剂量（0.3mg/kg，n = 6）Indo或安慰剂（稀释剂，n = 9）预处理后，使其暴露于分级缺氧环境（氧气含量：7.1 - 0.4微摩尔O₂/毫升）。在所有三组中，随着氧气含量值降低，全脑和局部脑血流量均显著增加（P < 0.01）。然而，在所有脑区中，高剂量组与低剂量组相比，随着氧气含量值降低，脑血流量曲线的上升显著更低（P < 0.05），在尾端区域影响最大。此外，安慰剂处理动物的脑血流量曲线与低剂量组相似。在所有缺氧范围内，三组的脑氧代谢率（CMR(O₂)）和葡萄糖代谢均得以维持，直到高剂量组达到严重缺氧（氧气含量≤1.1微摩尔O₂/毫升）时，CMR(O₂)降低（P < 0.05），葡萄糖代谢增加（P < 0.05）。高剂量组在严重缺氧期间的平均动脉血压为45mmHg（P > 0.05）。虽然三组中脑血流量与CMR(O₂)的耦合得以维持，但高剂量预处理后这种关联发生了显著改变。我们得出结论，Indo对缺氧诱导的脑灌注的减弱具有剂量依赖性。在严重缺氧期间，高剂量预处理会观察到CMR(O₂)和葡萄糖代谢的改变，且安慰剂和低剂量Indo预处理对缺氧的反应相似。
