Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, NC 27710, USA.
J Appl Physiol (1985). 2012 Jul;113(2):224-31. doi: 10.1152/japplphysiol.00308.2012. Epub 2012 May 3.
Intravenous perfluorocarbon (PFC) emulsions, administered with supplemental inspired O(2), are being evaluated for their ability to eliminate N(2) from blood and tissue prior to submarine escape, but these agents can increase the incidence of central nervous system (CNS) O(2) toxicity, perhaps by enhancing O(2) delivery to the brain. To assess this, we infused a PFC emulsion (Oxycyte, 6 ml/kg iv) into anesthetized rats and measured cerebral Po(2) and regional cerebral blood flow (rCBF) in cortex, hippocampus, hypothalamus, and striatum with 100% O(2) at 1, 3, or 5 atmospheres absolute (ATA). At 1 ATA, brain Po(2) stabilized at >20 mmHg higher in animals infused with PFC emulsion than in control animals infused with saline, and rCBF fell by ~10%. At 3 ATA, PFC emulsion raised brain Po(2) >70 mmHg above control levels, and rCBF decreased by as much as 25%. At 5 ATA, brain Po(2) was ≥159 mmHg above levels in control animals for the first 40 min but then rose sharply; rCBF showed a similar profile, reflecting vasoconstriction followed by hyperemia. Conscious rats were also pretreated with PFC emulsion at 3 or 6 ml/kg iv and exposed to 100% O(2) at 5 ATA. At the lower dose, 80% of the animals experienced seizures by 33 min compared with 50% of the control animals. At the higher dose, seizures occurred in all rats within 25 min. At these doses, administration of PFC emulsion poses a clear risk of CNS O(2) toxicity in conscious rats exposed to hyperbaric O(2) at 5 ATA.
静脉内全氟碳 (PFC) 乳剂，与补充吸入的 O(2) 一起使用，正在评估其在潜艇逃生前从血液和组织中消除 N(2) 的能力，但这些药物会增加中枢神经系统 (CNS) O(2) 毒性的发生率， 也许是通过增强大脑的 O(2) 输送。为了评估这一点，我们给麻醉大鼠静脉内输注 PFC 乳剂 (Oxycyte，6 ml/kg)，并用 100% O(2) 在 1、3 或 5 个大气压绝对 (ATA) 下测量皮质、海马、下丘脑和纹状体的脑 Po(2) 和局部脑血流量 (rCBF)。在 1 ATA 下，与输注生理盐水的对照组相比，输注 PFC 乳剂的动物的脑 Po(2)稳定在 20 mmHg 以上，rCBF 下降约 10%。在 3 ATA 下，PFC 乳剂使脑 Po(2)比对照水平升高 70 mmHg 以上，rCBF 下降高达 25%。在 5 ATA 下，脑 Po(2)在最初 40 分钟内比对照组动物高≥159 mmHg，但随后急剧升高；rCBF 呈现出相似的模式，反映出血管收缩 followed 随后的充血。清醒大鼠还在 3 或 6 ml/kg 静脉内预先用 PFC 乳剂处理，并在 5 ATA 下暴露于 100% O(2)。在较低剂量下，80%的动物在 33 分钟时出现癫痫发作，而对照组动物中有 50%出现癫痫发作。在较高剂量下，所有大鼠在 25 分钟内均出现癫痫发作。在这些剂量下，在 5 ATA 下暴露于高压 O(2)时，PFC 乳剂的给药对清醒大鼠的中枢神经系统 O(2) 毒性构成明显风险。
