[Acute effects of human recombinant erythropoietin on cardiovascular dynamics and vasoactive substances].
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.
Suga
M
M
2nd Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Kurihara
S
S
Iino
Y
Y
Terashi
A
A
D000804:Angiotensin II / Q000097:blood*; D004298:Dopamine / Q000097:blood; D016232:Endothelins / Q000097:blood; D004837:Epinephrine / Q000097:blood; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology
D016232:Endothelins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000804:Angiotensin II; D004298:Dopamine; D004837:Epinephrine