Liachenko S, Tang P, Hamilton R L, Xu Y
Department of Anesthesiology, University of Pittsburgh, PA 15261, USA.
Stroke. 1998 Jun;29(6):1229-38; discussion 1238-9. doi: 10.1161/01.str.29.6.1229.
Because noninvasive physiological monitoring of cerebral blood flow, metabolic integrity, and brain ion and water homeostasis can now be accomplished with new, state-of-the-art MR spectroscopy and imaging techniques, it is appropriate to develop controllable and reproducible animal models that permit prolonged circulatory arrest and resuscitation in the magnet and also allow for studies of long-term survival and outcome. We have developed such a model in rats that involves minimal surgical preparations and can achieve resuscitation remotely within precisely controlled time.
Cardiac arrest was induced by asphyxiation, the duration of which ranged from 8 to 24 minutes. Resuscitation was achieved remotely by a slow, intra-aortic infusion of oxygenated blood (withdrawn either from the same rat before asphyxia or from a healthy donor rat) along with a resuscitation cocktail containing heparin (50 U/100 g), sodium bicarbonate (0.1 mEq/100 g), and epinephrine (4 micrograms/100 g). The body temperature was measured by a tympanic thermocouple probe and was controlled either by a heating pad (constant tympanic temperature = 37 degrees C) or by warm ambient air (constant air temperature = 37 degrees C). Interleaved 31P/1H nuclear magnetic resonance (NMR) spectroscopy was used in a selected group of rats to measure the cerebral metabolism before and during approximately 20 minutes of circulatory arrest and after resuscitation.
The overall success rate of resuscitation, irrespective of the duration of cardiac arrest, was 82% (51 of 62). With a programmed infusion pump, the success rate was even higher (95%). The survival time for rats subjected to 15 and 19 minutes of asphyxia with core temperature tightly controlled was significantly lower than that with ambient temperature control (P < 0.001 and P < 0.04, respectively). High-quality NMR spectra can be obtained continuously without interference from the resuscitation effort. Final histological examinations taken 5 days after resuscitation showed typical neuronal damages, similar to those found in other global ischemia models.
Because the no-flow time and resuscitation time can be precisely controlled, this outcome model is ideally suited for studies of ischemic and reperfusion injuries in the brain and possibly in other critical organs, permitting continuous assessment of long-term recovery and follow-up in the same animals.
由于现在可利用新的、先进的磁共振波谱和成像技术对脑血流量、代谢完整性以及脑离子和水平衡进行无创生理监测，因此开发可控且可重复的动物模型是合适的，该模型应能在磁体中实现长时间循环骤停和复苏，还能用于长期存活和转归的研究。我们已在大鼠中开发出这样一种模型，其手术准备极少，且能在精确控制的时间内远程实现复苏。
通过窒息诱导心脏骤停，持续时间为8至24分钟。通过缓慢主动脉内输注含氧血液（取自窒息前的同一只大鼠或健康供体大鼠）以及含有肝素（50 U/100 g）、碳酸氢钠（0.1 mEq/100 g）和肾上腺素（4微克/100 g）的复苏混合液远程实现复苏。通过鼓膜热电偶探头测量体温，并通过加热垫（鼓膜恒定温度 = 37℃）或温暖的环境空气（恒定空气温度 = 37℃）进行控制。在一组选定的大鼠中，使用交错式31P/1H核磁共振（NMR）波谱在循环骤停约20分钟期间及复苏前后测量脑代谢。
无论心脏骤停持续时间如何，复苏的总体成功率为82%（62只中的51只）。使用程控输液泵时，成功率更高（95%）。核心温度严格控制的情况下，窒息15分钟和19分钟的大鼠存活时间显著低于环境温度控制组（分别为P < 0.001和P < 0.04）。可连续获得高质量的NMR波谱，不受复苏操作干扰。复苏5天后进行的最终组织学检查显示典型的神经元损伤，与其他全脑缺血模型中的损伤相似。
由于无血流时间和复苏时间可精确控制，该转归模型非常适合用于研究脑以及可能其他重要器官的缺血和再灌注损伤，允许在同一动物中持续评估长期恢复情况并进行随访。
