N-G-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, REVERSES INTERLEUKIN-2-INDUCED HYPOTENSION
N-G-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, REVERSES INTERLEUKIN-2-INDUCED HYPOTENSION
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DOI：
10.1097/00003246-199506000-00005
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发表时间：
1995-06-01
影响因子：
8.8
通讯作者：
LOGOTHETIS, CJ
中科院分区：
文献类型：
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作者：
KILBOURN, RG;FONSECA, GA;LOGOTHETIS, CJ
评价n- g -甲基- l-精氨酸作为白介素-2 （IL-2）诱导的高动力休克调节剂的作用。设计：一项前瞻性、实验性临床研究。环境：三级医疗中心的重症监护室。患者：3例转移性肾细胞癌患者在第一个疗程中出现低血压，使用高剂量IL-2 (18 × 10（6) IU/m(2)/天，连续输注5天）。干预措施：当患者在随后的IL-2治疗中出现低血压时，给予12 mg/kg的n - g -甲基- l-精氨酸。此后，根据需要，每4小时给药4 mg/kg，以维持收缩压在100 mm hg以上。测量和主要结果：在开始使用IL-2治疗前，进行有创血流动力学监测。使用配对t检验分析n - g -甲基- l-精氨酸给药前和给药后15m的差异。n - g -甲基- l精氨酸（12 mg/kg）具有显著的降压作用（平均血压从87 +/- 4增加到121 +/- 7 mm Hg），同时全身血管阻力（549 +/- 51增加到860 +/- 167达因秒/cm(5)）和肺血管阻力（81 +/- 16增加到117 +/- 29达因秒/cm(6)）增加。心脏指数的下降也被记录下来（4.5 +/- 0.5至3.6 +/- 0.3 L/min/m），肺动脉闭塞和中心静脉压没有明显变化(2)，维持剂量为4 mg/kg的n - g -甲基-L-精氨酸诱导了类似的血流动力学结果，尽管n - g -甲基-L-精氨酸的降压作用持续时间随着剂量的增加而减少。结论：一氧化氮合成抑制剂n - g -甲基- l-精氨酸可逆转IL-2诱导的血流动力学效应。这些结果为n - g -甲基- l-精氨酸单独应用于低血压患者的生物活性提供了证据。虽然在这项初步研究中没有观察到不良反应，但毒性和有效性问题需要在正式的临床试验中进一步确定。n - g -甲基- l-精氨酸可能在调节细胞因子引起的极度血管舒张或脓毒性休克中发挥治疗作用。
To evaluate the role of N-G-methyl-L-arginine as a modulator of the hyperdynamic shock induced by the administration of interleukin-2 (IL-2).Design: A prospective, pilot clinical study.Setting: Intensive care unit of a tertiary care center.Patients: Three sequential patients with metastatic renal cell carcinoma who developed hypotension during their first course of treatment with high-dose IL-2 (18 x 10(6) IU/m(2)/day by continuous infusion for 5 days).Interventions: Upon developing hypotension during their subsequent therapy with IL-2, patients were administered 12 mg/kg of N-G-methyl-L-arginine. Thereafter, a dose of 4 mg/kg was given every 4 hrs, as needed, to maintain the systolic blood pressure above 100 mm Hg.Measurements and Main Results: Invasive hemodynamic monitoring was instituted before the initiation of treatment with IL-2. Differences noted before, and 15 mim after, the administration of N-G-methyl-L-arginine were analyzed using the paired t-test.N-G-methyl-L arginine (12 mg/kg) induced a significant antihypotensive effect (mean blood pressure increased from 87 +/- 4 to 121 +/- 7 mm Hg), accompanied by an increase of the systemic vascular resistance (549 +/- 51 to 860 +/- 167 dyne sec/cm(5)) and pulmonary vascular resistance (81 +/- 16 to 117 +/- 29 dyne sec/cm(6)). A decrease in the cardiac index was also documented (4.5 +/- 0.5 to 3.6 +/- 0.3 L/min/m(2)), No significant changes in pulmonary artery occlusion and central venous pressures were observed, Maintenance doses of 4 mg/kg of N-G-methyl-L-arginine induced similar hemodynamic results, although the duration of the antihypotensive effect of N-G-methyl-l-arginine decreased with sequential doses.Conclusions: The hemodynamic effects induced by IL-2 administration are reversed by N-G-methyl-L-arginine, a nitric oxide synthesis inhibitor. These results provide evidence for the biological activity of N-G-methyl-L-arginine when administered alone to hypotensive patients. While no adverse effects were observed in this preliminary study, issues of toxicity and effectiveness need to be defined further in formal clinical trials. N-G-methyl-L-arginine may play a therapeutic role in the modulation of the extreme vasodilation induced by cytokine administration or in septic shock.