Effects of Intravenous Administration of Recombinant Human Erythropoietin in Rats Subject to Hemorrhagic Shock

Buemi, Michele; Allegra, Alessandro; Squadrito, Francesco; Buemi, Anna L.; Laganà, Angela; Aloisi, Carmela; Frisina, N

doi:10.1159/000187526

Cited by 21 publications

(16 citation statements)

References 10 publications

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“…On studying the blood flow of the human pretibial muscle by means of 133 Xe clearance, Buemi et al [22] found an EPO-induced reduction in postischemic vasodilation. Moreover, in anesthetized rats subjected to hemorrhagic shock by intermittent bleeding, EPO administration significantly increased the mean arterial pressure, the survival time, and the percentage of animals surviving with respect to untreated controls [23] . EPO also seems to be able to inhibit acetylcholine-induced cutaneous vasodilation and can stimulate the endothelial release of endothelin and inhibit nitric oxide, a potent vasodilator [24] .…”

Section: Ph: the Erythropoietin (Epo) Rolementioning

confidence: 90%

“…Remodeling operated by endothelial progenitor cells [17] In vivo effect on the PAP of polycythemia [21] Structural adaptation to hematological viscosity enhancement [18,20] Acute EPO administration in shocked rats [23] Interstitial and perivascular fibrosis [29] Upregulation of EPO receptor in the lung vessels [30] Clinical Models Acute EPO administration in shocked humans [25] Acute EPO administration in chronic cor pulmonale [26] …”

Section: Animal Modelsmentioning

confidence: 99%

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Pulmonary Hypertension and Erythropoietin

Buemi

Senatore²,

Gallo³

et al. 2007

Kidney Blood Press Res

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Numerous uremic patients on hemodialysis have pulmonary hypertension attributable to the presence of arteriovenous fistulas, vascular calcification, and endothelial dysfunction due to alterations in the balance between vasoconstrictive and vasodilatory substances. For these reasons, the effects of recombinant human erythropoietin, a drug widely used in patients on dialysis, on the pulmonary circulation were studied. Some authors maintain that recombinant human erythropoietin has an antihypertensive effect, while others have observed that this hormone induces a reduction in pulmonary arterial pressure due to its vasoactive and stimulatory effects on endothelial and smooth muscle cell precursors.

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Section: Ph: the Erythropoietin (Epo) Rolementioning

confidence: 90%

Section: Animal Modelsmentioning

confidence: 99%

Pulmonary Hypertension and Erythropoietin

Buemi

Senatore²,

Gallo³

et al. 2007

Kidney Blood Press Res

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“…The hormone, in fact, seems to be able to modify the kinetics of platelets and of the white cells [I], and it seems able to considerably modify endothelial activity [2] and vascular tone [3,4]. In previous studies.…”

Section: Doses Of Recombinant Erythropoietinmentioning

confidence: 99%

In vivo evaluation of leukocyte distribution by means of technetium 99M after intravenous administration of high doses of recombinant erythropoietin

et al. 1996

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In previous studies. we proved that the administration of high doses of erythropoietin can cause a rapid and transient leukopenia, caused by a preferential, even if not exclusive, lymphocyte reduction 151. Our histological study, carried out on rats in which erythropoietin administration caused a rapid and transient neutropenia, did not provide evidence for a margination of the cells on the walls of the great vessels like the aorta 151.As a similar leukopenia was shown after granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF). and interleukin-2 (L-2) administration, and, as in this case, it was proved that the leukopenia was caused by the leukocyte sequestrum at the pulmonary level, we wanted to investigate the possibility that a similar mechanism was responsible for the leukopenia induced by erythropoietin 16.7.8.91.Our study was conducted on 2 voluntary healthy subjects. after their informed consent.To each of them was administrated, after a 12-hr fast, 20,000 U i.v. of erythropoietin in bolus, and at -15 min, 0.5 min, 15 min. 30 min, 60 min, 90 min, and 120 min blood was drawn for estimation of leukocyte count and formula. As pointed out in previous studies, an administration of high doses of erythropoietin causes leukopenia, reaching statistical significance at 60 min and completely regressing at 12U min [S].This study of leukocyte behavior was carried out by isolating white cells with a fractionated centrifugation with hespan, and then labelling the cells with a solution containing technetium 99m (Ceretec 99m Tc examezatime, Amersham. Italy). Then the cells were reinfused and their distribution was noticed by gamma camera at stages of 0 min. 5 min, 30 min, 60 min and 120 min. Erythropoietin administration was carried out shortly after labelled leukocyte reinfusion.No particular distribution pattern of radiolabelled cells was evident in these scans, neither in the early ones (able to demonstrate an eventual pulmonary sequestrum of the leukocytes). nor in the later ones, able to demonstrate evidence of liver or splenic accumulation.Therefore, on the basis of the above-mentioned data, it seems we can rule out that leukopenia induced by erythropoietin can be ascribed to a sequestrum action of the white cells in a particular organ, like the lung or the splanchnic organs.It is probable, instead, that leukopenia is secondary to a lymphocyte adhesion to the walls of the whole microcirculation. This hypothesis is supported by a recent study in which we showed that an administration of high doses of erythropoietin could modify in a significant way serum concentrations of soluble E-selectine and the intercellular adhesion molecule 1 (sICAM-1) [lo]. Further studies will describe more precisely the mechanism and physiopathologic significance of the extraerythropoietic actions of erythropoietin.

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“…The vasoactive action of erythropoietin was also recently utilized in extreme hemodynamic conditions occurring during hemorrhagic shock [12]. The study was conducted on anesthetized rats, in which irreversible hemorrhagic shock was obtained through intermittent bleeding of the artery for 20 min, until a mean arterial pressure of 25–30 mm Hg was achieved.…”

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confidence: 99%