Erythropoietin Modified the Cardiac Action of Ouabain in Chronically Anaemic-Uraemic Rats

Wald, Miriam; Gutnisky, A; Borda, Enri; Sterin‐Borda, Leonor

doi:10.1159/000188711

Cited by 29 publications

(20 citation statements)

References 24 publications

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“…Changes in echocardiographic parameters were unrelated to levels of hematocrit achieved, rHuEPO dosage administered, duration of therapy, blood pressure, and antihypertensive drugs employed, all factors that may influence cardiac function [11]. These observations could, therefore, suggest a primary effect of rHuEPO on myocardial contractile function, as it has been recently demonstrated in uremic rats [22]. Lack of erythropoietin in endstage renal disease may be at least in part responsible for the inhibition of cardiac enzymes, altering the contractile behavior of the heart.…”

Section: Discussionmentioning

confidence: 57%

Impact of Recombinant Human Erythropoietin Treatment on Left Ventricular Hypertrophy and Cardiac Function in Dialysis Patients

Massimetti¹,

Pontillo

Feriozzi³

et al. 1998

Blood Purif

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The results of anemia correction by recombinant human erythropoietin (rHuEPO) therapy with regard to cardiac function and left ventricular hypertrophy in dialysis patients are controversially discussed. The aim of the study was to assess the effects of therapy rHuEPO on cardiac morphology and function in dialysis patients. We studied 11 clinically stable hemodialysis patients with severe renal anemia (hematocrit <27%) and increased left ventricular mass index (LVMi) with no history of coronary or valvular heart disease, systemic disease, severe hyperparathyroidism, hypertension stage 2 or higher, transfusion-dependent anemia, and concurrent rHuEPO treatment. The patients were treated with rHuEPO administered subcutaneously once or twice weekly at a mean dose of 80 ± 31 IU/kg week until the hematocrit was >30% and underwent a complete Doppler echocardiographic study at baseline and at follow-up (after 12.2 ± 2.9 months). At follow-up, ejection fraction and fractional shortening significantly increased from 62.7 ± 13.8 to 67.8 ± 9.7% (p < 0.05) and from 35.5 ± 9.8 to 39.4 ± 7.1% (p < 0.05), respectively, whereas mean velocity of circumferential fiber shortening demonstrated a trend towards amelioration from 1.18 ± 0.23 to 1.27 ± 0.27 circ/s (n.s.). LVMi and morphological data remained unchanged throughout the study. Nevertheless, LVMi changes showed two different behaviors with respect to baseline values: in 6 patients with higher baseline values, LVMi decreased from 229 ± 36 to 191 ± 45 g/m² (p < 0.05), while it worsened in 5 patients with less marked LVMi, increasing from 141 ± 32 to 186 ± 40 g/m² (p < 0.05). Our data demonstrate that partial correction of renal anemia with rHuEPO therapy seems to improve cardiac performance and to induce a regression of left ventricular hypertrophy, particularly in patients with greater baseline hypertrophy, ultimately confirming the multifactorial pathogenesis of left ventricular hypertrophy.

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Section: Discussionmentioning

confidence: 57%

Impact of Recombinant Human Erythropoietin Treatment on Left Ventricular Hypertrophy and Cardiac Function in Dialysis Patients

Massimetti¹,

Pontillo

Feriozzi³

et al. 1998

Blood Purif

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“…Epo is known to have effects not only in erythropoiesis and thrombopoiesis 21,22 but also on many other cells and tissues, including endothelial cells, 26 smooth muscle cells, 27,28 cardiomyocytes, 29 and kidney cells, 30 as well as neuroprotective and suppressive actions in ischemia-induced neuronal cell death as neurogenic and neuroprotective agents via antiapoptotic, neurotrophic, antioxidant, and angiogenic effects. 10,13,31,32 Our study, however, showed that brain weight was significantly reduced in the Epoetin-treated group as compared with Epo-bp-and ␣Epo-bp-treated groups ( Table 1).…”

Section: Discussionmentioning

confidence: 99%

Prevention of Erythropoietin-Associated Hypertension

Lee

2007

Hypertension

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Abstract-Hypertension is the most significant complication from treatment with erythropoietin (Epo). Can Epo-induced hypertension be eliminated? We examined systemic and local effects of our genetically engineered products, Epo-binding protein (Epo-bp) and anti-Epo-bp antibodies, on randomly assigned Sprague-Dawley rats at midnight, 4 AM, 8 AM, noon, 4 PM, and 8 PM. Blood pressure, hematocrit, and body weight were measured immediately before and after the completion of a 4-week, twice-weekly course of Epo (50 U/kg), Epo-bp, anti-Epo-bp antibodies, or physiological saline injections. Epo treatment increased hematocrit markedly overall as compared with the saline, Epo-bp, and anti-Epo-bp antibody groups (0.616 versus 0.427, 0.439, and 0.441, respectively) and at each of the 6 test times (all PϽ0.0001). Epo-bp and anti-Epo-bp antibody treatment with Epo had almost no effect on the Epo-induced hematocrit increase (0.616 versus 0.580 or 0.591, respectively

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“…Erythropoietin has also been shown to exert direct cytoprotective effects on cardiomyocytes through stimulation of the erythropoietin receptor and the phosphatidylinositol 3-kinase/Akt signaling pathway (4,46). In a rat model of myocardial infarction, treatment with DARB induced angiogenesis and improved left ventricular (LV) function (42).…”

mentioning

confidence: 99%

Darbepoetin-α prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure

Rastogi

Imai

Sharov

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Rastogi S, Imai M, Sharov VG, Mishra S, Sabbah HN. Darbepoetin-␣ prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure. Am J Physiol Heart Circ Physiol 295: H2475-H2482, 2008. First published October 24, 2008 doi:10.1152/ajpheart.00074.2008.-In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-␣ (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) ϳ25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 g/kg, n ϭ 7) or to no therapy (HF, n ϭ 7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1␣, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1␣ and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia. erythropoietin; anemia; ventricular remodeling; stem cells MANY PATIENTS with congestive heart failure (HF) are anemic or exhibit hemoglobin levels near the lower limit of normal (12). The severity of HF has been shown to positively correlate with the degree of anemia (38,45). The kidneys represent the main site of the synthesis of erythropoietin, the most important hormone regulating erythropoiesis (18,19). Darbepoetin-␣ (DARB) is a derivative of erythropoietin that contains two more carbohydrate groups than the native protein and increase its half-life by threefold compared with recombinant erythropoietin. DARB has been shown to be efficacious in maintaining hemoglobin levels in anemic patients (24). Clinical trials have shown that in anemic patients with HF, DARB increases and maintains hemoglobin and improves health-related quality of life and exercise duration (29,44).Erythropoietin has also been shown to possess a host of other nonerythropoietic properties including the ability to stimulate angiogenesis (20), attenuate apoptosis and hypoxia (28,41), and mobilize bone marrow-derived stem cells (BMSCs) (1, 2). Erythropoietin has also been shown to exert direct cytoprotective effects on cardiomyocytes through stimulation of the erythropoietin receptor and the phosphatidylinositol 3-kinase/Akt signaling pathway (4,46). In a rat model of my...

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Erythropoietin Modified the Cardiac Action of Ouabain in Chronically Anaemic-Uraemic Rats

Cited by 29 publications

References 24 publications

Impact of Recombinant Human Erythropoietin Treatment on Left Ventricular Hypertrophy and Cardiac Function in Dialysis Patients

Impact of Recombinant Human Erythropoietin Treatment on Left Ventricular Hypertrophy and Cardiac Function in Dialysis Patients

Prevention of Erythropoietin-Associated Hypertension

Darbepoetin-α prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure

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