Cahn R, Cahn J
SIR international, Department of Experimental Therapy, Montrouge, France.
Pharmacology. 1988;36(3):156-65. doi: 10.1159/000138379.
Cerebral hemodynamic and metabolic changes, occurring during delayed hypoperfusion following transient cerebral ischemia, and the influence of treatment with almitrine plus raubasine were studied in mongrel dogs. 10 min of transient cerebral ischemia was induced by bilateral clamping of both carotid and vertebral arteries. After declamping, the mean time necessary until cerebral venous PO2 (cvPO2) reached a value of 3.6 kPa, threshold for tissue hypoxia, was 80 min. At this time (T0), venous cerebral blood flow (vCBF) and cerebral perfusion pressure (Perf P) were below (60 and 20%, respectively) preischemic values, while cerebral vascular resistance (CVR) and oxygen and glucose extraction rates increased despite a normal cerebral oxygen consumption (CMRO2). At T0 ventilatory assistance without (control group) or with (treated group) intravenous infusion of almitrine plus raubasine was applied for 110 min. Between T0 and T110 min, 2 dogs died in the control group. During this period vCBF decreased by more than 60% in the control group while it slightly increased in the treated group. A strong decrease in Perf P (40%) and increase in CVR (140%) was observed in the control group while in the treated group Perf P and CVR slightly decreased (14 and 35%, respectively). CMRO2 decreased by 60% in the control group but remained within the normal range in the treated group. The fact that cvPO2 remained constantly below the initial value of 3.6 kPa in the control group and, on contrary, above this value in the group infused with raubasine plus almitrine indicates that the vCBF improvement leads to an increase in oxygen supply and is involved in the keeping of the adequacy between flow and metabolism. Our results support the hypothesis that the post-ischemic syndrome may play an important role in the acute prognosis of stroke. They clearly indicate that early cerebral resuscitation by infusion of almitrine plus raubasine, maintaining oxygen availability and CBF above initial thresholds, should improve the long-term neurological outcome.
在杂种犬中研究了短暂性脑缺血后延迟性低灌注期间发生的脑血流动力学和代谢变化，以及阿米三嗪加萝巴新治疗的影响。通过双侧夹闭颈动脉和椎动脉诱导10分钟的短暂性脑缺血。松开夹闭后，脑静脉血氧分压（cvPO2）达到组织缺氧阈值3.6 kPa所需的平均时间为80分钟。此时（T0），脑静脉血流量（vCBF）和脑灌注压（Perf P）分别低于缺血前值（分别为60%和20%），而脑血管阻力（CVR）以及氧和葡萄糖提取率增加，尽管脑氧耗量（CMRO2）正常。在T0时，对对照组不进行通气辅助，对治疗组静脉输注阿米三嗪加萝巴新并进行通气辅助，持续110分钟。在T0至T110分钟期间，对照组有2只犬死亡。在此期间，对照组的vCBF下降超过60%，而治疗组的vCBF略有增加。对照组观察到Perf P显著下降（40%）和CVR增加（140%），而治疗组的Perf P和CVR略有下降（分别为14%和35%）。对照组的CMRO2下降了60%，但治疗组的CMRO2仍保持在正常范围内。对照组cvPO2持续低于初始值3.6 kPa，相反，在输注萝巴新加阿米三嗪的组中cvPO2高于该值，这一事实表明vCBF的改善导致氧供应增加，并参与维持血流与代谢之间的平衡。我们的结果支持以下假设：缺血后综合征可能在中风的急性预后中起重要作用。它们清楚地表明，通过输注阿米三嗪加萝巴新进行早期脑复苏，维持氧供应和CBF高于初始阈值，应能改善长期神经功能结局。
