Hall E D, Travis M A
CNS Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Exp Neurol. 1988 Mar;99(3):594-606. doi: 10.1016/0014-4886(88)90176-8.
Experimental subarachnoid hemorrhage was produced in chloralose-anesthetized cats by slow injection of 0.5 ml/kg autologous arterial blood into the cisterna magna. As a result, there was an initial (within 5 min) 25.1% decrease in caudate nuclear blood flow as measured by hydrogen clearance. Between 5 min and 3 h postinjection, there was a further and progressive 25.9% decline in caudate blood flow. The hemorrhage also caused a slow increase in intracranial pressure, a decrease in cerebral perfusion pressure, and an increase in caudate vascular resistance. In contrast, the administration of a single 30 mg/kg i.v. dose of methylprednisolone sodium succinate 30 min after the acute hemorrhage resulted in stabilization of caudate blood flow and vascular resistance and some restoration of those parameters toward prehemorrhage values. This effect was not correlated with a decrease in intracranial pressure or an increase in cerebral perfusion pressure. A 15 mg/kg i.v. dose of the drug had only a slight effect on caudate blood flow. A 60 mg/kg i.v. dose, while initially supportive, lost its effect during the later stages of the experiment, indicating a sharp biphasic dose-response relationship for the effect of methylprednisolone on caudate blood flow after subarachnoid hemorrhage. However, of the three doses, only 60 mg/kg significantly decreased the slow posthemorrhage rise in intracranial pressure. The beneficial effect of the 30 mg/kg i.v. dose of the drug on caudate blood flow, separate from an effect on the slow rise in intracranial pressure, suggests that the steroid support of caudate perfusion is due to a direct protective effect of the drug on the microvasculature. Based on previous studies showing an identical dose-response pattern for the ability of methylprednisolone to prevent posttraumatic lipid peroxidation of central nervous system tissue and progressive ischemia development, the possibility of the drug's inhibition of hemorrhage-initiated vasoconstrictor prostanoid action and microvascular lipid peroxidation is proposed.
在氯醛糖麻醉的猫身上，通过向小脑延髓池缓慢注射0.5毫升/千克自体动脉血来制造实验性蛛网膜下腔出血。结果，通过氢清除法测量，尾状核血流量最初（5分钟内）下降了25.1%。在注射后5分钟至3小时之间，尾状核血流量进一步逐渐下降了25.9%。出血还导致颅内压缓慢升高、脑灌注压降低以及尾状核血管阻力增加。相比之下，急性出血30分钟后静脉注射单次30毫克/千克剂量的甲泼尼龙琥珀酸钠可使尾状核血流量和血管阻力稳定，并使这些参数部分恢复至出血前水平。这种作用与颅内压降低或脑灌注压升高无关。静脉注射15毫克/千克剂量的该药物对尾状核血流量只有轻微影响。静脉注射60毫克/千克剂量，虽然最初有支持作用，但在实验后期失去了效果，表明甲泼尼龙对蛛网膜下腔出血后尾状核血流量的影响呈明显的双相剂量反应关系。然而，在这三个剂量中，只有60毫克/千克能显著降低出血后颅内压的缓慢升高。静脉注射30毫克/千克剂量的该药物对尾状核血流量的有益作用，与对颅内压缓慢升高的作用无关，这表明类固醇对尾状核灌注的支持作用是由于该药物对微血管的直接保护作用。基于先前的研究显示甲泼尼龙预防中枢神经系统组织创伤后脂质过氧化和渐进性缺血发展的能力具有相同的剂量反应模式，提出了该药物抑制出血引发的血管收缩性前列腺素作用和微血管脂质过氧化的可能性。
