Lu Aigang, Clark Joseph F, Broderick Joseph P, Pyne-Geithman Gail J, Wagner Kenneth R, Khatri Pooja, Tomsick Thomas, Sharp Frank R
Department of Neurology, Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH 45267-0532, USA.
Exp Neurol. 2009 Apr;216(2):407-12. doi: 10.1016/j.expneurol.2008.12.020. Epub 2009 Jan 7.
A major complication of recanalization therapy after an acute arterial occlusion in brain is hemorrhagic transformation (HT). Although it is known that prolonged ischemia is important in the development of HT, the role of reperfusion in ischemia-reperfusion induced HT is less well studied. To address the effect of reperfusion on HT, we assessed the incidence and severity of hemorrhage in rats after 5 h of middle cerebral artery occlusion (MCAO) followed by 19-hour reperfusion compared to rats with permanent occlusion (PMCAO) at the same 24-hour time point. The incidence and amount of hemorrhage, neurological function, and mortality rates were measured. MCAO (5 h) with 19-hour reperfusion was associated with a significantly higher incidence of cortical hemorrhage compared to PMCAO (81.8% vs 18.2%, p<0.05). Hemorrhage scores were higher in the 5-hour MCAO/reperfusion group compared to PMCAO rats (17.6+/-11.5 vs 2.4+/-5.3 in cortex, 20.4+/-4.6 vs 9.7+/-4.5 in striatum, p<0.01). Neurological function was worse in the ischemia-reperfusion group compared to PMCAO (p<0.05) and mortality rates were insignificantly higher in the 5-hour MCAO/reperfusion group vs PMCAO group (54.5% vs 18.1%; p<0.08). The results suggest that reperfusion after prolonged ischemia is associated with increased hemorrhagic transformation and neurological deterioration as compared to permanent ischemia. Whether pharmacological treatments prior to reperfusion attenuate post-ischemic HT requires further study.
脑急性动脉闭塞后再通治疗的一个主要并发症是出血性转化(HT)。虽然已知长时间缺血在HT的发生中很重要,但再灌注在缺血-再灌注诱导的HT中的作用研究较少。为了探讨再灌注对HT的影响,我们评估了大脑中动脉闭塞(MCAO)5小时后再灌注19小时的大鼠与在相同24小时时间点永久性闭塞(PMCAO)的大鼠的出血发生率和严重程度。测量了出血的发生率和出血量、神经功能及死亡率。与PMCAO相比,MCAO(5小时)再灌注19小时的大鼠皮质出血发生率显著更高(81.8%对18.2%,p<0.05)。5小时MCAO/再灌注组的出血评分高于PMCAO大鼠(皮质:17.6±11.5对2.4±5.3,纹状体:20.4±4.6对9.7±4.5,p<0.01)。与PMCAO相比,缺血-再灌注组的神经功能更差(p<0.05),5小时MCAO/再灌注组的死亡率略高于PMCAO组(54.5%对18.1%;p<0.08)。结果表明,与永久性缺血相比,长时间缺血后的再灌注与出血性转化增加和神经功能恶化有关。再灌注前的药物治疗是否能减轻缺血后HT仍需进一步研究。