Slinko Siarhei, Caspersen Casper, Ratner Veniamin, Kim Jin-Ji, Alexandrov Paul, Polin Richard, Ten Vadim S
Department of Pediatrics, Division of Neonatology, Columbia University, New York, New York 10032, USA.
Pediatr Res. 2007 Jul;62(1):65-70. doi: 10.1203/PDR.0b013e3180676cad.
Postnatal d 7 (p7) or p12 mice had their right carotid artery (CA) and jugular vein (JV) ligated to mimic veno-arterial (VA) access for extracorporeal membrane oxygenation (ECMO). At p9-11 (early) or p19-21 (late) mice were exposed to hyperthermia or normothermia followed by assessment of neuropathological injury score. In separate cohorts of mice, cerebral and peripheral blood flow (CBF, PBF) and cerebral ATP content was measured. Hyperthermia resulted in ischemic brain injury in 57% and 77% of mice subjected to early or late hyperthermia, respectively. Isolated CA+JV ligation induced minimal injury (score 0.47 +/- 0.34) in 2/8 mice from the late normothermia group. No cerebral injury was detected in mice subjected to early normothermia. In 3/19 shams (2/10 early, 1/9 late) hyperthermia induced a subtle (score, 0.6 +/- 0.27) injury in the ipsilateral to the site of surgery cortex. CBF and PBF increased in response to hyperthermia in all mice. The rise in CBF was significantly attenuated in the "ligated" versus intact hemisphere, which was associated with a profound depletion of ATP content. Systemic hyperthermia induces ischemic brain injury in mice with ligated CA+JV. We speculate that hyperthermia/fever can be a potential risk factor for brain injury in infants treated with VA ECMO.
出生后第7天（p7）或第12天（p12）的小鼠，其右侧颈动脉（CA）和颈静脉（JV）被结扎，以模拟体外膜肺氧合（ECMO）的静脉-动脉（VA）通路。在出生后第9 - 11天（早期）或第19 - 21天（晚期），小鼠接受高温或正常体温处理，随后评估神经病理损伤评分。在另一组小鼠中，测量脑血流和外周血流（CBF、PBF）以及脑ATP含量。高温分别导致早期或晚期高温处理的小鼠中57%和77%出现缺血性脑损伤。单独的CA + JV结扎在晚期正常体温组的2/8只小鼠中引起最小损伤（评分为0.47±0.34）。早期正常体温处理的小鼠未检测到脑损伤。在3/19只假手术小鼠中（早期10只中有2只，晚期9只中有1只），高温在手术侧皮质同侧引起轻微损伤（评分为0.6±0.27）。所有小鼠的CBF和PBF在高温处理后均增加。与完整半球相比，“结扎”半球的CBF升高明显减弱，这与ATP含量的显著消耗有关。全身高温可在结扎CA + JV的小鼠中诱发缺血性脑损伤。我们推测高温/发热可能是接受VA ECMO治疗的婴儿发生脑损伤的潜在危险因素。
