Sterz F, Safar P, Diven W, Leonov Y, Radovsky A, Oku K
Department of Anesthesiology, University of Pittsburgh, PA 15260.
Resuscitation. 1993 Apr;25(2):137-60. doi: 10.1016/0300-9572(93)90091-4.
We and others hypothesized that noxious substances released after prolonged cardiac arrest from malfunctioning liver, kidneys, or intestine (e.g. bacterial toxins, aromatic amino acids), might hamper recovery of the brain. The highly detoxifying effect of hemabsorption (i.e. hemoperfusion) with microencapsulated activated carbon has been demonstrated in other diseases. We used our dog model of ventricular fibrillation cardiac arrest of 15 min (n = 2 x 4) or 12.5 min (n = 2 x 6), reversed by brief (high flow) cardiopulmonary bypass (CPB). In half of the dogs in each insult group, a charcoal filter (HemoKart) was inserted into the circuit of CPB at low flow, from start of reperfusion to 4 h. Intermittent positive pressure ventilation was to 20 h and intensive care to 96 h after cardiac arrest. Bacterial blood cultures were positive in most of the dogs in both groups 30 min to 20 h after cardiac arrest (but not later) and were uninfluenced by hemabsorption. In the control groups to 4 h after cardiac arrest, serum levels of potentially injurious aromatic amino acids (e.g. phenylalanine, tyrosine) and of branched-chain/aromatic amino acid ratios, remained unchanged. From 12 to 48 h after cardiac arrest, aromatic amino acid levels increased (worsened). The branched-chain/aromatic amino acid ratios changed accordingly in the opposite direction. In the hemabsorption groups to 4 h after cardiac arrest, all amino acid levels were reduced, aromatic amino acids more so than branched-chain amino acids, thus increasing (improving) the ratio, compared with controls (P < 0.01). There was no group difference after discontinuance of hemabsorption at 4 h. Outcome in terms of overall performance categories and neurologic deficit scores from 24 to 96 h and brain histopathologic damage scores 96 h after cardiac arrest, were not significantly different between groups. The lack of a beneficial outcome effect of hemabsorption to 4 h after cardiac arrest does not support the self-intoxication hypothesis. The amino acid levels later after cardiac arrest suggest that more prolonged hemabsorption and more encompassing detoxification treatments, such as plasma phoresis or total body blood washout, might be evaluated.
我们和其他研究人员推测，心脏骤停持续较长时间后，肝脏、肾脏或肠道功能失常所释放的有害物质（如细菌毒素、芳香族氨基酸）可能会妨碍大脑的恢复。微囊化活性炭血液吸附（即血液灌流）的高效解毒作用已在其他疾病中得到证实。我们使用了犬心室颤动心脏骤停15分钟（n = 2×4）或12.5分钟（n = 2×6）的模型，通过短暂（高流量）体外循环（CPB）进行复苏。在每个损伤组的半数犬中，从再灌注开始至4小时，将一个炭滤器（血液灌流器）以低流量插入CPB回路。心脏骤停后间歇性正压通气至20小时，重症监护至96小时。两组中大多数犬在心脏骤停后30分钟至20小时（但之后没有）血培养呈阳性，且不受血液吸附的影响。在心脏骤停后4小时内的对照组中，潜在有害的芳香族氨基酸（如苯丙氨酸、酪氨酸）的血清水平以及支链/芳香族氨基酸比值保持不变。心脏骤停后12至48小时，芳香族氨基酸水平升高（恶化）。支链/芳香族氨基酸比值相应地朝相反方向变化。在心脏骤停后4小时内的血液吸附组中，所有氨基酸水平均降低，芳香族氨基酸降低得比支链氨基酸更多，因此与对照组相比，比值升高（改善）（P < 0.01）。在4小时停止血液吸附后，两组之间没有差异。从心脏骤停后24至96小时的总体表现类别和神经功能缺损评分以及心脏骤停后96小时的脑组织病理损伤评分来看，两组之间没有显著差异。心脏骤停后4小时内血液吸附缺乏有益的结果效应，不支持自身中毒假说。心脏骤停后较晚时间的氨基酸水平表明，可能需要评估更长时间的血液吸附以及更全面的解毒治疗，如血浆置换或全身血液清洗。
