del Zoppo G J, Copeland B R, Anderchek K, Hacke W, Koziol J A
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Stroke. 1990 Apr;21(4):596-601. doi: 10.1161/01.str.21.4.596.
The effect of an intravenous infusion of recombinant tissue plasminogen activator on hemorrhagic transformation early after middle cerebral artery territory ischemia was studied in an established awake nonhuman primate (baboon) model. Following 3 hours' occlusion of the middle cerebral artery and 30 minutes' reperfusion in each of 30 baboons, a 60-minute infusion of recombinant tissue plasminogen activator (at three doses: Group A, 0.3 mg/kg, n = 6; Group B, 1.5 mg/kg, n = 6; Group C, 10 mg/kg, n = 6) or normal saline (n = 12) was undertaken. The frequency and volume of intracerebral hemorrhage, the volume of infarction, and clinical alterations were determined by computed tomography at 24 hours and 10 days, neuropathology at 14 days, and serial daily neurologic evaluations, respectively. Peripheral (nonintracranial) hemorrhage (Group A, p = 0.46; Group B, p = 0.015; Group C, p = 0.002) and peak plasma tissue plasminogen activator levels varied directly with the dose of recombinant tissue plasminogen activator. Petechial hemorrhagic infarction was a common finding among the 30 baboons. No significant differences in the incidences or volumes of infarction-related hemorrhage were apparent in any group compared with the respective saline-treated baboons. In pooled data, no significant relation between the volume of hemorrhage and the volume of infarction could be established. We conclude that the incidence and severity of hemorrhagic transformation are not related to infarction size and that recombinant tissue plasminogen activator does not increase the incidence or severity (volume) of hemorrhage when given early (less than or equal to 3.5 hours) after the onset of focal cerebral ischemia in this model.
在已建立的清醒非人类灵长类动物（狒狒）模型中，研究了静脉输注重组组织型纤溶酶原激活剂对大脑中动脉区域缺血后早期出血性转化的影响。在30只狒狒中，每只动物大脑中动脉闭塞3小时并再灌注30分钟后，进行60分钟的重组组织型纤溶酶原激活剂输注（三种剂量：A组，0.3mg/kg，n = 6；B组，1.5mg/kg，n = 6；C组，10mg/kg，n = 6）或生理盐水输注（n = 12）。分别通过24小时和10天时的计算机断层扫描、14天时的神经病理学检查以及每日连续的神经学评估来确定脑出血的频率和体积、梗死体积以及临床改变。外周（非颅内）出血（A组，p = 0.46；B组，p = 0.015；C组，p = 0.002）以及血浆组织型纤溶酶原激活剂峰值水平与重组组织型纤溶酶原激活剂的剂量直接相关。点状出血性梗死是30只狒狒中的常见表现。与各自接受生理盐水治疗的狒狒相比，任何一组中梗死相关出血的发生率或体积均无显著差异。在汇总数据中，无法确定出血体积与梗死体积之间的显著关系。我们得出结论，在该模型中，出血性转化的发生率和严重程度与梗死大小无关，并且在局灶性脑缺血发作后早期（小于或等于3.5小时）给予重组组织型纤溶酶原激活剂不会增加出血的发生率或严重程度（体积）。
