Ischemia triggered by red blood cell products in the subarachnoid space is inhibited by nimodipine administration or moderate volume expansion/hemodilution in rats
Ischemia triggered by red blood cell products in the subarachnoid space is inhibited by nimodipine administration or moderate volume expansion/hemodilution in rats
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DOI：
10.1097/00006123-200212000-00017
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发表时间：
2002-12-01
期刊：
影响因子：
4.8
通讯作者：
Dirnagl, U
中科院分区：
文献类型：
--
作者：
Dreier, JP;Windmüller, O;Dirnagl, U
目的：有人提出蛛网膜下腔出血后红细胞（RBC）产物可诱导迟发性缺血性神经功能缺损。用钙拮抗剂尼莫地平预防性治疗或预防全身容量收缩可减少迟发性缺血性神经功能缺损的发生。为了深入了解潜在的机制，我们研究了尼莫地平或容量扩张对大鼠红细胞产物诱导的缺血事件的影响。方法：在52只大鼠中植入颅窗。在窗口处，记录脑血流量（用激光多普勒血流仪测量）和蛛网膜下腔直流电位;用人工脑脊液灌注皮质表面。一个传播的神经元/星形胶质细胞的去极化波被触发在一个远程站点，从它前往颅window.Results：在16只大鼠，去极化波触发缺血事件在颅窗，当人工脑脊液中含有红细胞产品血红蛋白和升高的K+水平被灌流。相比之下，在接受静脉内施用尼莫地平（n = 12）或用羟乙基淀粉（6%羟乙基淀粉200/0.5）进行的适度容量扩张/血液稀释（n = 10）的动物中，去极化波在暴露于RBC产物的皮质区域中触发短暂的初始灌注不足，随后是短暂的充血。在生理条件下，去极化波触发短暂的充血（n = 14）。结论：红细胞产物引起的广泛性缺血是拮抗已知的措施，是有益的，在预防迟发性缺血性神经功能缺损。我们的研究结果表明，一个机制，涉及皮层微循环可能是尼莫地平和容量扩张的治疗效果。
OBJECTIVE: It has been proposed that delayed ischemic neurological deficits are induced by red blood cell (RBC) products after subarachnoid hemorrhage. Prophylac tic treatment with the Ca2+ antagonist nimodipine or prevention of systemic volume contraction reduces the occurrence of delayed ischemic neurological deficits. To gain insight into the underlying mechanism, we studied the effects of nimodipine or volume expansion on ischemic events induced by RBC products in rats.METHODS: A cranial window was implanted in 52 rats. At the window, cerebral blood flow (measured with laser Doppler flowmetry) and the subarachnoid direct current potential were recorded; the cortical surface was superfused with artificial cerebrospinal fluid. A spreading neuronal/astroglial depolarization wave was triggered at a remote site, from which it traveled to the cranial window.RESULTS: In 16 rats, the depolarization wave triggered-an ischemic event at the cranial window, when artificial cerebrospinal fluid containing the RBC product hemoglobin and elevated K+ levels was superfused. In contrast, in animals receiving intravenously administered nimodipine (n = 12) or moderate volume expansion/hemodilution with hydroxyethyl starch (6% hydroxyethyl starch 200/0.5) (n = 10), the depolarization wave triggered brief initial hypoperfusion, followed by brief hyperemia, in the cortical area exposed to the RBC products. Under physiological conditions, the depolarization wave triggered brief hyperemia (n = 14).CONCLUSION: Spreading ischemia induced by RBC products is antagonized by measures known to be beneficial in the prophylaxis of delayed ischemic neurological deficits. Our findings suggest that a-mechanism involving the cortical microcirculation might underlie the therapeutic effects of nimodipine and volume expansion.