Suga M, Kurihara S, Iino Y, Terashi A
2nd Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1996 Dec;38(12):634-9.
Treatment with human recombinant erythropoietin (r-EPO) can dramatically improve renal anemia, whereas it has been reported that such improved anemia may involve or worsen hypertension. When we administered a single dose of r-EPO at 9,000 units to 16 patients with end-stage renal failure requiring examination with a right cardiac catheter immediately before the introduction of dialysis, we measured cardiovascular dynamics and various vasoactive substances. The mean blood concentration of EPO was 3,035 units/ml 15 minutes after administration. As compared with the value of 107.6 +/- 3.2 mmHg obtained before administration, the mean arterial blood pressure significantly increased following the administration of r-EPO to 111.5 +/- 3.8 mmHg after 5 minutes, 112.4 +/- 4.2 mmHg after 10 minutes, 113.7 +/- 4.3 mmHg after 20 minutes, and 113.6 +/- 4.3 mmHg after 30 minutes (p < 0.05). The mean pulmonary arterial blood pressure tended to increase to 17.9 +/- 1.8 mmHg after 10 minutes from the level of 16.3 +/- 1.8 mmHg before administration (p = 0.096). The pulmonary vascular resistance index (PVRI) was 165.0 +/- 18.0 mmHg before administration and significantly increased to 193.2 +/- 19.0 and 199.0 +/- 16.6 dyn.S.cm-5.m2 after 10 and 30 minutes, respectively (p < 0.01, p < 0.05). The systemic vascular resistance index (SVRI) also significantly increased to 2,587 +/- 195 dyn.S.cm-5.m2 after 30 minutes from the level of 2,454 +/- 207 dyn.S.cm-5.m2 before administration (p < 0.05). Changes in SVRI showed a bimodal pattern, as with changes in PVRI. Angiotensin-II concentration significantly decreased to 13.7 +/- 4.4 pg/ml after 15 minutes from the level of 15.7 +/- 3.2 pg/ml before administration (p < 0.05). There were no significant changes in endothelin, prostaglandin, or adrenaline concentration after the administration of r-EPO. From these results, it was revealed that pulmonary intra-arterial administration of r-EPO has the acute effect of increasing pulmonary vascular resistance, thereby pointing to a direct effect of r-EPO in pulmonary vasoconstriction. Although no changes in vasoactive substances were observed in the present investigation, further studies with more sensitive measuring methods may be necessary.
用人重组促红细胞生成素（r-EPO）治疗可显著改善肾性贫血，然而，据报道这种改善的贫血可能会引发或加重高血压。我们对16例终末期肾衰竭患者在开始透析前立即给予9000单位单剂量的r-EPO，这些患者需要进行右心导管检查，我们测量了心血管动力学和各种血管活性物质。给药后15分钟，EPO的平均血药浓度为3035单位/毫升。与给药前测得的107.6±3.2 mmHg相比，r-EPO给药后平均动脉血压显著升高，5分钟后为111.5±3.8 mmHg，10分钟后为112.4±4.2 mmHg，20分钟后为113.7±4.3 mmHg，30分钟后为113.6±4.3 mmHg（p<0.05）。平均肺动脉血压给药后10分钟从给药前的16.3±1.8 mmHg升至17.9±1.8 mmHg，有升高趋势（p = 0.096）。给药前肺血管阻力指数（PVRI）为165.0±18.0 mmHg，给药后10分钟和30分钟分别显著升至193.2±19.0和199.0±16.6 dyn.S.cm-5.m2（p<0.01，p<0.05）。全身血管阻力指数（SVRI）给药后30分钟也从给药前的2454±207 dyn.S.cm-5.m2显著升至2587±195 dyn.S.cm-5.m2（p<0.05）。SVRI的变化与PVRI的变化一样呈双峰模式。血管紧张素-II浓度给药后15分钟从给药前的15.7±3.2 pg/ml显著降至13.7±4.4 pg/ml（p<0.05）。r-EPO给药后内皮素、前列腺素或肾上腺素浓度无显著变化。从这些结果可以看出，肺动脉内给予r-EPO具有增加肺血管阻力的急性作用，从而表明r-EPO对肺血管收缩有直接作用。尽管在本研究中未观察到血管活性物质的变化，但可能需要用更灵敏的测量方法进行进一步研究。
