losartan-potassium and Cardiomegaly

Topics: Acclimatization; Altitude; Animals; Animals, Domestic; Blood Coagulation Factors; Blood Pressure; Blood Viscosity; Blood Volume; Carbon Dioxide; Cardiac Output; Cardiomegaly; Cats; Cattle; Colorado; Coronary Circulation; Dogs; Erythrocyte Count; Erythropoietin; Guinea Pigs; Heart Rate; Humans; Hypertension, Pulmonary; Hypoxia; Indians, South American; Myocardium; Organ Size; Oxygen; Oxygen Consumption; Partial Pressure; Peru; Physical Exertion; Polycythemia; Pulmonary Circulation; Pulmonary Diffusing Capacity; Rabbits; Rats; Vascular Resistance

The mechanism underlying the anti‑inflammatory or antifibrotic activity of erythropoietin (EPO) in myocardial fibrosis (MF) remains elusive. In the current study, abdominal aortic constriction (AAC) was performed on rats and EPO and/or Toll‑like receptor (TLR)4 were overexpressed in rat hearts through intramyocardial administration of lentivirus expressing the EPO and TLR4 genes. Hematoxylin and eosin staining and Masson's trichrome staining were performed on tissue sections from rat hearts for histopathological examination. ELISA was used to determine the levels of inflammatory mediators in serum. Gene expression levels were determined by quantitative polymerase chain reaction analysis and protein expression levels were determined by western blot analysis and immunofluorescence staining. The results indicated that EPO overexpression improved MF in rat hearts, by inhibiting the release of transforming growth factor (TGF)‑β1, tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β, IL‑17A, matrix metalloproteinase (MMP)‑9 and MMP‑2. Moreover, EPO overexpression suppressed the expression of TLR4, while promoting phosphoinositide 3‑kinase (PI3K) and phosphorylated AKT serine/threonine kinase 1 (Akt) expression levels. However, the beneficial effects of EPO were attenuated by overexpression of TLR4. In addition, inhibition of PI3K/Akt signaling activity by treatment with LY294002 markedly reversed the protective effect of EPO on the AAC‑induced MF. Taken together, the present study demonstrated that EPO may have a critical role against MF by activating PI3K/Akt signaling and by downregulating TLR4 expression, thereby inhibiting the release of TGF‑β1, TNF‑α, IL‑6, IL‑1β, IL‑17A, MMP‑9 and MMP‑2. These findings suggest that the PI3K/Akt/TLR4 signaling pathway is associated with the anti‑inflammatory effects of EPO and may play a role in attenuating AAC‑induced MF.

Topics: Animals; Cardiomegaly; Cytokines; Erythropoietin; Fibrosis; Gene Expression Regulation; Inflammation; Inflammation Mediators; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardium; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Toll-Like Receptor 4; Transforming Growth Factor beta1

The use of recombinant human erythropoietin (rhEPO) to promote repair and minimize cardiac hypertrophy after myocardial infarction has had disappointing outcomes in clinical trials. We hypothesized that the beneficial non-hematopoietic effects of rhEPO against cardiac hypertrophy could be offset by the molecular changes initiated by rhEPO itself, leading to rhEPO resistance or maladaptive hypertrophy. This hypothesis was investigated using an isoproterenol-induced model of myocardial infarct and cardiac remodelling with emphasis on hypertrophy. In h9c2 cardiomyocytes, rhEPO decreased isoproterenol-induced hypertrophy, and the expression of the pro-fibrotic factors fibronectin, alpha smooth muscle actin and transforming growth factor beta-1 (TGF-β1). In contrast, by itself, rhEPO increased the expression of fibronectin and TGF-β1. Exogenous TGF-β1 induced a significant increase in hypertrophy, which was further potentiated by rhEPO. Exogenous fibronectin not only induced hypertrophy of cardiomyocytes, but also conferred resistance to rhEPO treatment. Based on these findings we propose that the outcome of rhEPO treatment for myocardial infarction is determined by the baseline concentrations of fibronectin and TGF-β1. If endogenous fibronectin or TGF-β levels are above a certain threshold, they could cause resistance to rhEPO therapy and enhancement of cardiac hypertrophy, respectively, leading to maladaptive hypertrophy.

Topics: Animals; Cardiomegaly; Cell Line; Erythropoietin; Fibronectins; Isoproterenol; Rats; Recombinant Proteins; Transforming Growth Factor beta

The objective of this study was to examine the hypothesis that hypertensive hypertrophy is vulnerable to infarction and defective in cytoprotective mechanisms by modification of intracellular signaling and mitochondrial proteins. Myocardial infarction was induced by 20-minute coronary occlusion/reperfusion in spontaneously hypertensive stroke-prone rats (SHR-SPs) and their controls (Wistar-Kyoto rats [WKYs]). Infarct size expressed as a percentage of area-at-risk was larger by 29% in SHR-SPs than in WKYs. Pretreatment with erythropoietin (EPO) significantly limited infarct size in WKYs but not in SHR-SPs. Ca(2+) retention capacity of mitochondria, an index of the threshold for opening of the mitochondrial permeability transition pore, on reperfusion was reduced in SHR-SPs compared with that in WKYs. Suppression of reactive oxygen species by N-(2-mercaptopropionyl)-glycine increased Ca(2+) retention capacity after reperfusion and limited infarct size in SHR-SPs to levels in WKYs. EPO induced phosphorylation of Akt, extracellular signal-related kinase, and glycogen synthase kinase-3β in the myocardium in both WKYs and SHR-SPs. EPO enhanced interaction of phospho-glycogen synthase kinase-3β and adenine nucleotide translocase on reperfusion in WKYs, although such an effect of EPO was not detected in SHR-SPs. The results suggest that enhanced opening of mitochondrial permeability transition pores by reactive oxygen species and modification of the signal downstream of phospho-glycogen synthase kinase-3β in the mitochondria underlie the increased vulnerability to infarction and the lack of anti-infarct tolerance by EPO, respectively, in hypertensive hypertrophied hearts.

Topics: Animals; Calcium; Cardiomegaly; Erythropoietin; Hypertension; Male; Mitochondria, Heart; Mitochondrial ADP, ATP Translocases; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Infarction; Myocardium; Protein Serine-Threonine Kinases; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; Risk Factors; Tiopronin

Pre-operative treatment with recombinant human erythropoietin may improve aortic stenosis patients' condition, including anemia and/or cardiac dysfunction, for subjecting to aortic valve replacement. In this study, we tested this hypothesis in a mouse model of aortic stenosis. Adult male mice were subjected to either aortic stenosis created by aortic ligature or sham operation. Aortic stenosis for 4 weeks caused cardiac hypertrophy, pulmonary congestion and left ventricular dysfunction. It was associated with increased levels of tumor necrosis factor-alpha in serum and myocardium, and reduced levels of interleukin-10 in myocardium but not in serum. Myocyte apoptosis rate, level of cleaved caspase 3, activity of nuclear factor-kappaB and expression of p38-MAPK pathway were also elevated. Erythropoietin treatment increased hematocrit but did not prevent the development of cardiac hypertrophy. It, however, reduced the apoptosis, prevented the increases in tumor necrosis factor-alpha, nuclear factor-kappaB activation and phosphorylation of p38, and attenuated the increases in lung weight, the decreases in LVEF and LVFS, and the increases in LVDd and LVDs. In conclusion recombinant human erythropoietin has cardioprotective effects in maladaptive cardiac hypertrophy by inhibiting nuclear factor-kappaB activation, phosphorylation of p38-MAPK pathway, and production of tumor necrosis factor-alpha, together leading to a reduced apoptosis.

Topics: Animals; Aortic Valve Stenosis; Apoptosis; Apoptosis Regulatory Proteins; Cardiomegaly; Cardiotonic Agents; Disease Models, Animal; Erythropoietin; Ligation; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Recombinant Proteins; Tumor Necrosis Factor-alpha

Mobilization of bone marrow-derived stem cells (BMCs) was shown to have protective effects after myocardial infarction (MI). However, the classical mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after revealing an impaired homing capacity. In the search for superior cytokines, erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in a murine model of surgically induced MI the influence of EPO treatment on survival and functional parameters as well as BMC mobilization, homing, and effect on resident cardiac stem cells (CSCs). Human EPO was injected intraperitoneally after ligation of the left anterior descendens (LAD) for 3 days with a total dose of 5000 IU/kg 6 and 30 days after MI, and pressure volume relationships were investigated in vivo. Cardiac tissues were analyzed by histology. To show the effect on BMCs and CSCs, FACS analyses were performed. Homing factors were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. EPO-treated animals showed a significant improvement of survival post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic parameters associated with attenuated remodeling, enhanced neovascularization, and diminished apoptotic cells in the peri-infarct area were improved. BMC subpopulations (CD31(+), c-kit(+), and Sca-1(+) cells) were mobilized, and homing of Sca-1(+) and CXCR4(+) BMCs toward an SDF-1 gradient into the ischemic myocardium was enhanced. However, there was no beneficial effect on CSCs. We have shown that EPO application after MI shows cardioprotective effects. This may be explained by mobilization of BMCs, which are homing via the CXCR-4/SDF-1 axis. However, EPO has no beneficial effects on resident CSCs. Therefore, new treatment regimes using EPO together with other agents may combine complementary beneficial effects preventing ischemic cardiomyopathy.

Topics: Animals; Antigens, CD34; Bone Marrow Cells; Cardiomegaly; Cell Movement; Chemokine CXCL12; Erythropoietin; Female; Immunohistochemistry; Leukocyte Common Antigens; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Receptors, CXCR4; Stem Cells; Survival Rate; Time Factors

Erythropoietin (EPO) is a haematopoietic hormone that has been confirmed as a novel cardioprotective agent. In this study, we test the hypothesis that EPO inhibits angiotensin-II (Ang-II)-induced hypertrophy in cultured neonatal rat cardiomyocytes.. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of EPO on Ang-II-induced hypertrophy in vitro. The surface area and mRNA expression of atrial natriuretic (ANF) myocytes were employed to detect cardiac hypertrophy. A phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and an endothelial nitric oxide synthase (eNOS) inhibitor L-NAME were also employed to detect the underlying mechanism of EPO. Intracellular signal molecules, such as Akt (PKB), phosphorylated Akt, eNOS and transforming growth factor-beta1 (TGF-beta1) protein expression were determined by Western blot. Nitric oxide (NO) levels in the supernatant of cultured cardiomyocytes were assayed using an NO assay kit.. The results indicate that EPO significantly attenuates Ang-II-induced hypertrophy shown as inhibition of increases in cell surface area and ANF mRNA levels. NO production was also increased proportionally in the EPO-treated group. EPO enhanced Akt activation and eNOS protein expression, whereas LY294002 or L-NAME partially abolished the anti-hypertrophic effect of EPO, accompanied by a decrease in Akt activation, eNOS protein expression and/or a reduction of NO production. EPO also down-regulated the protein expression of TGF-beta1.. We conclude that EPO attenuates cardiac hypertrophy via activation of the PI3K-Akt-eNOS-NO pathway and the down-regulation of TGF-beta1.

Topics: Angiotensin II; Animals; Animals, Newborn; Atrial Natriuretic Factor; Base Sequence; Blotting, Western; Cardiomegaly; Cells, Cultured; DNA Primers; Erythropoietin; Heart; In Vitro Techniques; Myocardium; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphatidylinositol 3-Kinases; Polymerase Chain Reaction; Proto-Oncogene Proteins c-akt; Rats; RNA, Messenger

This study was intended to elucidate the efficacy of an erythropoietin analog in cardiorenal dysfunction syndrome using a rodent model. Cardiorenal dysfunction was induced using doxorubicin hydrochloride (DXR). Lower doses (3 microg/kg) and higher doses (30 microg/kg) of darbepoetin alfa (DA) were used for intervention. Blood examinations for creatinine, blood urea nitrogen, iron, and hemoglobin were performed until 11 weeks after starting DA administration. Urine collection was performed 10 weeks after starting DA, and protein, iron, and N-acetyl-beta-D-glucosaminidase levels and antioxidation capacity of DA were determined. The dry left ventricular heart weight was measured, when the animals were sacrificed 11 weeks after starting DA administration. Histological analyses were performed for interstitial fibrotic changes and iron deposition in the kidney. Administration of DA markedly improved anemia to the normal control level and significantly alleviated DXR-induced increases of creatinine, blood urea nitrogen, renal interstitial fibrosis, renal iron deposition, and dry left ventricular weight, but serum and urinary iron and urinary protein and N-acetyl-beta-D-glucosaminidase levels were unchanged. The urinary total radical-trapping antioxidant capacity was improved to the normal control level in DA-treated animals. DA reduced the DXR-induced cardiorenal injury. This improvement was achieved, when anemia was corrected to the normal control level.

Topics: Acetylglucosaminidase; Animals; Antioxidants; Cardiomegaly; Darbepoetin alfa; Doxorubicin; Erythrocyte Count; Erythropoietin; Heart Diseases; Heart Ventricles; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Transferrin

Transgenic (tg) mice with chronic overexpression of the human erythropoietin gene are characterized by an increased hematocrit of about 0.80 in adulthood. This is accompanied by cardiac dysfunction and premature death. The aim of this study was to examine whether this cardiac dysfunction was accompanied by hypertrophy of the heart with remodeling of the extracellular matrix (ECM).. 3-months-old wild type (wt) and tg mice without cardiac hypertrophy were compared with the respective 7-months-old mice. The mRNA of brain natriuretic peptide (BNP), of the matrix metalloproteinases (MMP)-2, -8, -9, -13, of the tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, -4 and of collagen I and III was detected by ribonuclease protection assay. The activity of MMPs was measured by zymography.. There was hypertrophy of both ventricles in 7-months-old tg mice, which was accompanied by elevated mRNA expression of BNP. MMP-2 activity was increased and MMP-9 activity was decreased in the left ventricle (LV) of 3-months-old tg mice. This was accompanied by elevated TIMP-4 expression, followed by a shift of collagen mRNA expression from type III to type I in this ventricle.. The shift to collagen I in the heart of tg mice might be associated with a stiffer ventricle resulting in diastolic dysfunction. This may be responsible for a relative and intermittent LV- and right ventricle (RV)-insufficiency which was likely to have occurred as evidenced by the elevation of lung and liver weight with hemorrhage and interstitial fibrosis after 7 months.

Topics: Animals; Cardiomegaly; Collagen; Down-Regulation; Erythropoietin; Extracellular Matrix; Gene Expression; Heart Ventricles; Humans; Liver; Lung; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Mice; Mice, Transgenic; Natriuretic Peptide, Brain; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Up-Regulation

Left ventricular size and function were evaluated in 15 anemic chronic hemodialysis patients before and after the administration of recombinant human erythropoietin (rHuEPO). All patients were studied with two-dimensional and M-mode echocardiographic examinations before the initiation of rHuEPO (T1) and at 28 +/- 7 weeks of rHuEPO therapy (T2). The two-dimensional targeted M-mode echocardiographic measurements obtained were: end-diastolic dimension (EDD); end-systolic dimension (ESD); stroke dimension (SD); dimensional shortening (SD/EDD); systolic posterior wall thickness (PWs); diastolic posterior and interventricular septal thickness; end-systolic wall stress (ESWS); and left ventricular mass. Mean hematocrit in these patients increased almost 50%. The EDD decreased from a mean value (+/- SEM) of 6.41 +/- 0.33 to 4.93 +/- 0.21 cm (p less than 0.05). ESD decreased from a mean value of 4.16 +/- 1.2 to 2.77 +/- 0.06 cm (p less than 0.05). The calculated mean SD decreased slightly but not significantly from 2.21 +/- 0.69 to 2.19 +/- 0.60 cm. The calculated SD/EDD increased from a mean 0.35 +/- 0.09 to 0.44 +/- 0.07 (p less than 0.05). ESWS fell from 59.2 +/- 12.2 to 37.6 +/- 9.3 gm/cm2 (p less than 0.01), and left ventricular mass fell (p less than 0.05) from 347 +/- 15.2 to 227 +/- 59 gm. There was no significant difference in resting heart rate or systolic blood pressure between T1 and T2. The increase in dimension shortening reflects afterload reduction, as indicated by the fall in end-systolic wall stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anemia; Cardiomegaly; Echocardiography; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

The course of left ventricular hypertrophy was investigated in anemic hemodialysis patients treated with recombinant human erythropoietin (r-huEPO). 12 patients, aged 60.8 +/- 9.9 years (mean +/- SD) were treated for 18.8 +/- 2.7 months. Left ventricular size was estimated by echocardiography performed before treatment and at least 12 months after relieving anemia. Patients had signs of left ventricular and/or asymmetric septal hypertrophy when compared with a nonanemic and normotensive control group matched for sex and age. At baseline, hemoglobin (Hb) was 8.6 +/- 0.7 g/dl; interventricular septum thickness (IVST) was 1.75 +/- 0.34 cm, left ventricular posterior wall thickness (LVPWT) 1.32 +/- 0.19 cm, left ventricular muscle mass index (LVMI) 222.7 +/- 41 g/m2 and blood pressure (BP) 146.4 +/- 10/81.6 +/- 6 mm Hg. Hb rose to 11.4 +/- 1.2 g/dl (p less than 0.001); IVST and LVMI decreased to 1.42 +/- 0.35 cm (p less than 0.02) and 155.4 +/- 25.1 g/m2 (p less than 0.001); LVPWT and BP remained unchanged (1.30 +/- 0.26 cm and 146.8 +/- 16.9/81.2 +/- 7.8 mm Hg) at the end of the study. During the observation period, two groups of 5 and 7 patients differed from each other. The group of 5 patients had higher BP values (158.9 +/- 9.8/86.5 +/- 5.3 vs. 140.0 +/- 9.5/79.2 +/- 6.8 mm Hg, p less than 0.01), and the period with Hb values above 10 g/dl was shorter (14.5 +/- 2.4 vs. 17.8 +/- 2.4 months, p less than 0.05). These 5 patients failed to show a significant decrease in IVST and LVMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Analysis of Variance; Anemia; Blood Pressure; Cardiomegaly; Echocardiography; Erythropoietin; Female; Heart Ventricles; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Reference Values; Renal Dialysis; Time Factors; Ventricular Function, Left

Long-term myocardial effects of recombinant human erythropoietin (rhEPO) therapy were investigated in nine hemodialysis (HD) patients greater than 60 years of age. Echocardiographic studies were performed before the administration of rhEPO with a hematocrit of 20.8% +/- 1.9% and repeated after 6 (period I) and 24 months (period II) of treatment, when the hematocrit was increased to 34.1% +/- 2.3% and 32.3% +/- 2.8%, respectively. Left ventricular diameters were not significantly changed by rhEPO, although they tended to decrease at the end of the study (30.6 +/- 5.3 v 27.7 +/- 3.6 mm systole, and 50.3 +/- 3 v 46.5 +/- 3.7 mm diastole). Thickness of the interventricular septum and left ventricular posterior wall remained unaltered, although there was a downward trend (14.5 +/- 5.2 to 12.8 +/- 2.8 mm and 11.7 +/- 1.9 to 10.6 +/- 1.4 mm, respectively). Left ventricular mass index (LVM) progressively decreased from 181.5 +/- 61 to 153.8 +/- 38.3 (period I) and 135.7 +/- 45.6 g/m2 (period II, P less than 0.05). Stroke volume remained unaltered in period I, but it decreased from 93.7 +/- 10 to 65.2 +/- 12.8 mL (P less than 0.001) in period II, resulting in a decrease of cardiac index (CI) from 3.93 +/- 0.86 to 2.54 +/- 0.68 L/min/m2 (P less than 0.001) at the end of the study. Heart rate did not change during the study period. Blood pressure was kept constant, although antihypertensive therapy needed to be adjusted to prevent occurrence or aggravation of hypertension in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Anemia; Cardiomegaly; Echocardiography, Doppler; Erythropoietin; Female; Hematocrit; Hemodynamics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors

The substitution of recombinant human erythropoietin (rhEPO) in chronic hemodialysis patients is often associated with the development of severe hypertension. In the present study, a systematical echocardiographic analysis was performed in 25 patients on maintenance hemodialysis during rhEPO therapy for at least 4 months. Referred to the total group, indices of left ventricular size decreased significantly. Left ventricular total volume and left ventricular mass were reduced considerably. Fractional fiber shortening and ejection fraction showed an impressing improvement. At a constant heart rate, stroke volume and cardiac output were reduced. Myocardial thickness did not alter under chronic rhEPO therapy. When subgroups were formed with respect to changes in blood pressure, all parameters investigated behaved very similar to the total group, irrespective of changes in blood pressure. Five patients with coronary heart disease and clinical signs of myocardial insufficiency were evaluated separately. These patients showed a decrease in left ventricular size and no evidence of a deterioration of myocardial function. We conclude from our results that rhEPO therapy in patients on maintenance renal replacement therapy has beneficial effects on left ventricular size and function; these effects are not significantly counteracted by the development of hypertension.

Topics: Anemia; Cardiomegaly; Erythropoietin; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Ultrasonography; Ventricular Function, Left

To clarify the role of chronic anaemia in the pathogenesis of the left ventricular hypertrophy (LVH) of chronic uraemia, nine normotensive dialysed patients were studied before and 3 and 6 months after start of intravenous treatment with recombinant human erythropoietin (rHuEpo). M-Mode echocardiographic estimations of left ventricular mass indices (LVMi) and plasma noradrenaline determinations were made at 3 and 6 months, and total blood volume (TBV) only at 6 months. Resting haemoglobin values were 5.9 +/- 1.3 (SD) g/dl, increased within 3 months to 10.2 +/- 1.2 (P less than 0.001), then remained unchanged. Baseline LVMi was 115 +/- 18 g/m2 body surface area (b.s.a.) and decreased significantly (P less than 0.0025) over the entire period to a final value of 78 +/- 13 g, which did not differ from the average value for 19 healthy controls. Resting plasma noradrenaline was 1.45 +/- 0.44 pmol/ml and did not change significantly, although values were reduced at the 3rd month, when decreased heart rates and slightly and non-significantly increased blood pressures were recorded. TBV did not vary because the increased erythrocyte mass was compensated for by parallel decreases in plasma volume. These data demonstrate the existence of a cause-effect relationship between uraemic anaemia and LVH, although the precise mechanism remains unknown. Amelioration of anaemia with rHuEpo, by allowing recovery from the attendant LVH, might improve long-term cardiovascular prognosis in some dialysed uraemic patients.

Topics: Adult; Anemia; Cardiomegaly; Echocardiography; Erythropoietin; Female; Humans; Male; Middle Aged; Norepinephrine; Renal Dialysis; Uremia

Myocardial effects of recombinant human erythropoietin (rhEPO) treatment were prospectively investigated in 15 hemodialysis (HD) patients with severe anemia (hematocrit [Ht] 19.7 +/- 2.5%). Echocardiographic studies were performed after a midweek HD session just before and after a year of rhEPO. At the end of the study period, Ht had improved to 32.2 +/- 3.5% and cardiac index significantly decreased (5.48 +/- 1.54 vs 3.97 +/- 0.94 l/min/m2, p less than 0.001). Left ventricular mass index (LVMi) decreased with rhEPO (210.7 +/- 48.3 vs 139 +/- 50 g/m2, p less than 0.05). This decrease was concomitant with a decrease of LV end-diastolic diameter (4.89 +/- 0.44 vs 4.57 +/- 0.64 cm, p less than 0.05), interventricular septum thickness (IVST, 1.42 +/- 0.33 vs 1.07 +/- 0.13 cm, p less than 0.01) and LV posterior wall thickness (LVPWT, 1.28 +/- 0.21 vs 1.01 +/- 0.11 cm, p less than 0.01). Eight patients were hypertensive well controlled with hypotensive drugs (group I) and 7 normotensive (group II). LVMi was higher in group I than in group II before rhEPO (235.2 +/- 40 vs 182.7 +/- 43.1 g/m2, p less than 0.05) and significantly decreased after rhEPO in both groups (28.5% and 41.4% respectively). LVMi remained higher in group I than in group II at the end of the study (168.5 +/- 0.9 vs 106.7 +/- 24 g/m2, p less than 0.025). A moderately elevated IVST/LVPWT was reduced with a year of rhEPO (1.14 +/- 0.40 vs 1.05 +/- 0.15, p less than 0.05), disclosing correction of asymmetric septal hypertrophy. We conclude that left ventricular hypertrophy (LVH) regression is obtained after partial correction of anemia with rhEPO. Previous hypertension with current need of antihypertensive treatment has also a significant effect in the development of LVH. Whether this regression would improve outcome in HD patients remains to be established.

Topics: Adolescent; Adult; Anemia; Cardiomegaly; Combined Modality Therapy; Drug Evaluation; Echocardiography; Erythropoietin; Female; Hematocrit; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

The long-term cardiorespiratory effects of recombinant human erythropoietin treatment were investigated in ten haemodialysis patients by means of maximum exercise testing, lung function tests, echocardiography, chest X-ray, and rheological assessment over 12 months. There were significant rises in exercise time (mean [SD] 13.2 [5.5] to 20.0 [6.2] min), maximum oxygen consumption (19.1 [7.0] to 25.0 [6.7] ml.min-1.kg-1), and anaerobic threshold (11.7 [3.6] to 15.4 [4.8] ml.min-1.kg-1) after 2 months of erythropoietin treatment. The improvements were maintained but not augmented on repeat testing after 4, 8, and 12 months of therapy. Carbon monoxide transfer [corrected] rose from 15.5 (2.9) to 18.6 (3.7) ml.min-1.mm Hg-1. There was a substantial reduction in exercise-induced cardiac ischaemia (eight patients had significant ST segment depression before erythropoietin, only one after 2 months' treatment, and none after 12 months' treatment), despite a significant rise in whole blood viscosity. Left ventricular mass, as estimated by echocardiography, progressively decreased from 354 (169) g to 251 (95) g after 12 months' treatment, and four patients showed a reduction in cardiothoracic ratio on chest X-ray.

Topics: Adult; Aged; Anemia; Blood Gas Analysis; Cardiomegaly; Coronary Disease; Drug Administration Schedule; Drug Evaluation; Erythropoietin; Exercise Test; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxygen Consumption; Recombinant Proteins; Renal Dialysis; Respiratory Function Tests

Cardiomegaly and impaired cardiac function induced by renal anemia are frequent findings in patients with chronic renal failure. The present investigation was performed to study the cardiac effects of a therapy with recombinant human erythropoietin in patients on maintenance hemodialysis. Echocardiographic examinations showed a decrease in cardiac size and left-ventricular mass continuously over 12 months of effective erythropoietin substitution. Cardiac output was reduced, and ejection fraction and myocardial contractility increased. The development of aggravation of arterial hypertension did not counteract the beneficial effects of erythropoietin on cardiac performance.

Topics: Cardiomegaly; Echocardiography; Erythropoietin; Female; Heart; Humans; Hypertension; Male; Recombinant Proteins; Renal Dialysis; Time Factors

Cardiomegaly and impaired myocardial function are frequent in patients on maintenance hemodialysis. One important reason is probably severe renal anemia. Substitution with recombinant human erythropoietin (rhEPO) results in long-term correction of renal anemia. We investigated the changes in cardiac function under rhEPO therapy using echocardiography. 13 patients with severe renal anemia (hct less than 26%) but independent of regular blood transfusions during the last six months were treated with 40-120 IU/kg rhEPO intravenously three times/week. Echocardiographic studies were performed in the anemic state and when hematocrit values were stable at levels above 30%. Left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were reduced (LVEDD: 53.9 +/- 4.2 mm vs. 51.4 +/- 5.8 mm; LVESD: 35.7 +/- 5 mm vs. 32.8 +/- 5 mm). Mean end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were also diminished (LVEDV: 141.9 +/- 25.4 ml vs. 128.1 +/- 32.5 ml; LVESV: 54.8 +/- 18.6 ml vs. 45.1 +/- 17 ml). Stroke volume (SV) fell slightly from 87.1 ml to 83 ml resulting in a decrease of cardiac output (CO) from 6.9 +/- 1.6 l/min to 6.2 +/- 1.7 l/min. The thickness of the left ventricular posterior wall (LVPW) and of the septum interventriculare (IVS) remained constant. Myocardial contractility indicated by ejection fraction (EF), fractional shortening (FS) and the velocity of circumferential fiber shortening (VCF) frequently improved. Our data indicate that correction of renal anemia by rhEPO can improve myocardial function in patients on maintenance hemodialysis.

Topics: Anemia; Cardiomegaly; Echocardiography; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Myocardial Contraction; Recombinant Proteins; Renal Dialysis