losartan-potassium and Acidosis

Topics: Acidosis; Anemia; Bone Diseases, Metabolic; Chronic Disease; Darbepoetin alfa; Diabetic Nephropathies; Diet, Protein-Restricted; Erythropoietin; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Diseases; Male; Nephrology; Renin-Angiotensin System

Topics: Acidosis; Apoptosis; Brain Ischemia; Erythropoietin; Fever; Fibrinolytic Agents; Forecasting; Humans; Hyperglycemia; Myocardial Ischemia; Tissue Plasminogen Activator

Studies in rats with renal ablation indicate that anemia lessens, whereas its vigorous correction with recombinant human erythropoietin (r-HuEPO) worsens systemic and glomerular hypertension, factors known to promote progression of chronic renal failure (CRF). However, in human studies, use of r-HuEPO in predialysis patients has not been associated with worsening renal function, provided blood pressure control is achieved. Histological evidence of bone disease is common in early renal failure, and deficits in calcitriol synthesis seem to be an important factor in the pathogenesis of secondary hyperparathyroidism (HPTH) in early CRF. Reports to data, on the use of low dose active vitamin D metabolites in predialysis patients, indicate either a reversible decline or no decline in renal function. Adynamic bone disease, however, may ensure during such therapy if excessive reductions in serum intact parathyroid hormone concentrations occur. Recent data suggest that chronic metabolic acidosis decreases albumin synthesis, increases muscle proteolysis, and induces negative nitrogen balance in patients with CRF. Despite these experimental data, the clinical relevance of correction of metabolic acidosis in end-stage renal disease (ESRD) is still not defined. Even though therapy of metabolic acidosis in the adult patient with CRF remains conjectural at this time, reports indicate that its correction might lead to healing of osteomalacia and osteopenia, and possibly may decrease protein degradation and improve growth in children with CRF.

Topics: Acidosis; Adult; Anemia; Animals; Calcitriol; Calcium Compounds; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Erythropoietin; Humans; Kidney Failure, Chronic; Rats; Recombinant Proteins; Renal Dialysis

To investigate the relationship between erythropoietin concentration in umbilical venous blood and clinical signs of fetal hypoxia.. We measured erythropoietin concentrations in umbilical venous blood from 200 consecutively born neonates using an enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies. Results were available within 6 hours. Inter-assay variation was 8.5% and the mean intra-assay variation was 14.2%.. Using a multiple regression analysis, we found that the erythropoietin concentration correlated significantly (P < .01) with fetal growth retardation and umbilical acidosis but not with gestational age, meconium-stained amniotic fluid (AF), abnormal fetal heart rate (FHR) pattern, or Apgar score at 5 minutes. Median erythropoietin concentrations were 25.1 mU/mL in infants with no risk factors or complications during pregnancy and delivery (n = 19), 25.8 mU/mL after complicated pregnancy (n = 95), 50.6 mU/mL with meconium-stained AF (n = 12), 44.7 mU/mL with abnormal FHR pattern (n = 40), 47.8 mU/mL with both stained AF and abnormal FHR pattern (n = 10), and 72.6 mU/mL with umbilical acidosis (n = 24). The median erythropoietin concentration increased significantly with decreasing pH and with increasing base deficit in umbilical arterial blood. The erythropoietin concentration in umbilical venous blood (cutoff value 50 mU/mL) discriminated between infants with no clinical signs of fetal hypoxia and those with umbilical acidosis with a sensitivity of 75% and a specificity of 90%.. Elevated erythropoietin concentrations in umbilical venous blood indicate prolonged fetal hypoxia. The ELISA technique might be a useful tool for determining the exact time course of erythropoietin concentrations in fetal hypoxia.

Topics: Acidosis; Biomarkers; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Heart Rate, Fetal; Humans; Infant, Newborn; Pregnancy; Sensitivity and Specificity; Umbilical Veins

We aimed to study the haematopoietic response in normal and acidotic deliveries following vaginal and abdominal delivery and to compare this to the surrogate markers of perinatal acidosis. Blood gas analyses, complete blood pictures and erythropoietin assays were performed on umbilical or early neonatal blood samples. Placental sections were examined for the presence of nucleated red blood cells. Perinatal clinical risk factors and major neonatal outcomes were collected. The control population was 78 deliveries where the cord arterial pH was > 7.10. Controls born after labour were compared to those born prior to the onset of labour and to 14 acidotic infants born after labour. Nucleated red blood cells did not increase with labour in the control groups but were significantly higher (p < 0.05) in the acidotic group. Erythropoietin did not significantly change with either labour or acidosis. The predictive values from nucleated red blood cell counts were higher than those from low Apgar scores, atypical cardiotocograph traces, meconium-stained amniotic fluid, erythropoietin and the presence of nucleated red blood cells in placental sections. Nucleated red blood cell counts may be a useful surrogate marker of acidosis where blood gas analysis is unavailable. Further studies are required to examine the timing of the increase of erythropoiesis to help define the onset of the stimulus.

Topics: Acidosis; Asphyxia Neonatorum; Blood Gas Analysis; Chi-Square Distribution; Delivery, Obstetric; Erythrocyte Count; Erythropoietin; Female; Fetal Blood; Fetal Diseases; Fetal Monitoring; Hematopoiesis; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Obstetric Labor Complications; Pregnancy; Pregnancy Outcome; Probability; Reference Values; Sensitivity and Specificity

We evaluated in a double-blind randomized study the effect of epoetin beta (recombinant human erythropoietin) therapy on oxygen status in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. All 76 patients enrolled in this study were randomized to the two treatment groups (5 x 500 U epoetin beta or placebo/kg body weight intravenously over a 14-day period before surgery) and received 300 mg Fe2+ per day orally before surgery. Before and after surgery the lactate level and the following parameters according to the oxygen status algorithm by Siggaard-Andersen were evaluated: arterial oxygen tension (PaO2), effective hemoglobin concentration (ceHb), arterial oxygen saturation (SaO2), oxygen half saturation tension (p50), red cell 2.3 diphosphoglycerate (2.3 DPG), arterial total oxygen concentration (ctO2), concentration of extractable oxygen (cx), and oxygen compensation factor (Qx). Therapy with epoetin beta led to increases in ceHb, PaO2, ctO2, and cx and to a decrease in Qx before surgery (p < 0.05 for PaO2, p < 0.0001 for the other parameters vs placebo). The cx in patients who received epoetin beta rose by approximately 20%, thus indicating a considerable improvement in O2 delivery. In patients receiving placebo the hemoximetric parameters remained outside the normal limits at all times after surgery, but in the epoetin beta group PaO2, ctO2, cx, and Qx returned almost to their baseline values by the second or fifth postoperative day, even though the frequency of transfusions was significantly higher in the placebo group. Whereas p50 and 2.3 DPG fell in the placebo group after surgery, these two parameters were significantly higher in the epoetin beta group and led to a further increase in cx (from 24% to 38%) versus the placebo group as a result of the right shift in the hemoglobin O2-binding curve. The postoperative incidence and severity of lactic acidosis were higher in the placebo group. Preoperative epoetin beta therapy is a safe way of providing increased extractable O2 (by 24% to 38%) and decreasing the risk of lactic acidosis after surgery. This therapy has a more favorable effect on the O2 binding curve than the transfusion of erythrocyte concentrate and enhances the effect of epoetin beta therapy on the postoperative oxygen status.

Topics: Acidosis; Algorithms; Cardiac Surgical Procedures; Double-Blind Method; Erythropoietin; Female; Humans; Lactic Acid; Male; Middle Aged; Oxygen; Oxygen Consumption; Preoperative Care; Recombinant Proteins

Erythropoietin (EPO), originally identified for its critical hormonal role in promoting erythrocyte survival and differentiation, is a member of the large and diverse cytokine superfamily. Recent studies have identified multiple paracrineautocrine functions of EPO that coordinate local responses to injury by maintaining vascular autoregulation and attenuating both primary (apoptotic) and secondary (inflammatory) causes of cell death. Experimental evidence also supports a role for EPO in repair and regeneration after brain and spinal cord injury, including the recruitment of stem cells into the region of damage. Tissue expression of the EPO receptor is widespread, especially during development, and includes the heart. However, it is currently unknown as to whether EPO plays a physiological function in adult myocardial tissue. We have assessed the potential protective role of EPO in vitro with adult rat cardiomyocytes, and in vivo in a rat model of myocardial infarction with reperfusion. The results show that EPO markedly prevents the apoptosis of cultured adult rat myocardiocytes subjected to 28 h of hypoxia (approximately 3% normal oxygen). Additional studies employing a rat model of coronary ischemia-reperfusion showed that the administration of recombinant human EPO (5,000 units/kg of body weight; i.p. daily for 7 days) reduces cardiomyocyte loss by approximately 50%, an extent sufficient to normalize hemodynamic function within 1 week after reperfusion. These observations not only suggest a potential therapeutic role for recombinant human EPO in the treatment of myocardial ischemia and infarction by preventing apoptosis and attenuating postinfarct deterioration in hemodynamic function, but also predict that EPO is likely a tissue-protective cytokine in other organs as well.

Topics: Acidosis; Animals; Apoptosis; Cell Hypoxia; Erythropoietin; Hemodynamics; Humans; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Recombinant Proteins

In the present experiment we have studied the effect of exercise performed before and 24 h after withdrawal of 450 ml of blood on the serum erythropoietin and growth hormone (GH) levels, in humans. Twelve male subjects (x +/- SD) aged 23.2 +/- 2.6 y, with a body mass of 74.8 +/- 7.2 kg, height 178.0 +/- 7.6 cm, BMI 23.6 +/- 2.1 kg x m(-2), VO2 max 2937 +/- 324 ml x min(-1), participated in this study. The subjects performed twice an incremental exercise test until exhaustion, separated by a period of about 7 - 10 days. The second test was performed 24 h after withdrawal of 450 ml of blood (honorary blood donation). In the control study we found no effect of the incremental exercise on the serum erythropoietin concentration, which amounted to 14.24 +/- 7.66 mU x ml(-1) at rest and 14.97 +/- 6.07 mU x ml(-1) at the end of the incremental test. Serum GH level in the control study rose considerably from 0.158 +/- 0.024 nmol x l(-1) at rest to 1.523 +/- 0.336 nmol x l(-1) at the end of exercise and returned to initial value 2 h after the exercise. During the experiment performed 24 h after withdrawal of 450 ml of blood the serum erythropoietin concentration at rest was significantly elevated (p < 0.01) in relation to the control measurement (amounting to 24.85 +/- 13.60 mU x ml(-1)) and at the end of the incremental exercise a tendency towards further elevation (p = 0.09) in erythropoietin concentration up to 28.32 +/- 14.51 mU x m(-1) was observed. Serum GH level during the experiment after blood withdrawal was similar to that in control test and exercise caused a rise in the GH level to 1.056 +/- 0.52 nmol x l(-1), significantly less than in control test, but this increment fell to control value 2 h after exercise. The elevated level of erythropoietin 24 h after blood withdrawal was accompanied by a significant increase (p < 0.015) in blood hydrogen ion concentration [H +] b at rest from 48.2 +/- 2.8 nmol x l(-1) in the control study to 52.9 +/- 4.5 nmol x l(-1) after blood donation. No effect of blood withdrawal on pre-exercise level of plasma lactate concentration, end-tidal O2 and end-tidal CO2 was found. We concluded that withdrawal of 450 ml of blood, within 24 hours significantly increased serum erythropoietin concentration and caused non-lactic acidosis. A single bout of maximal incremental exercise, performed before and 24 hours after blood withdrawal, had no effect on serum erythropoietin concentration in humans but the exercise-induced increase in

Topics: Acidosis; Adult; Analysis of Variance; Blood Specimen Collection; Erythropoietin; Exercise; Exercise Test; Growth Hormone; Humans; Lactates; Male; Pulmonary Gas Exchange; Statistics, Nonparametric; Time Factors

Topics: Acidosis; Bicarbonates; Erythropoietin; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Sodium; Sodium Bicarbonate

Erythropoietin (EPO) production in response to hypoxic hypoxia is known to be attenuated by simultaneous hypercapnia. This study aimed to investigate whether this inhibitory effect of hypercapnia is 1) a direct effect of carbon dioxide or mediated by changes in pH or bicarbonate, 2) affects also carbon monoxide hypoxia, and 3) influences either the synthesis and release of EPO or the mechanisms by which hypoxia triggers an increase in EPO production rate. We found that EPO formation in mice exposed to normobaric hypoxia (8% O2) or to carbon monoxide (0.1%) was reduced by 30 and 42% when animals were simultaneously exposed to hypercapnia (7% CO2), by 35 and 38% when subjected to metabolic acidosis (NH4Cl), and unchanged when subjected to metabolic alkalosis (NaHCO3). In animals exposed to brief hypoxia (15 min) and subsequent normoxia (2 h), metabolic acidosis did not affect EPO levels when initiated after the hypoxic period. The results indicate that acidosis inhibits hypoxia-induced triggering of EPO formation independently of PCO2 and HCO3 levels. Because this inhibitory effect is also present during carbon monoxide hypoxia, it appears not solely due to potentiated hyperpnea. Alternatively, it may result from a facilitated intrarenal oxygen release or a direct effect at the EPO production sites.

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Animals; Carbon Monoxide; Erythropoietin; Hydrogen-Ion Concentration; Hypoxia; Male; Mice

To assess the immediate postnatal changes of serum immunoreactive erythropoietin (EP) in infants born after acute or chronic fetal hypoxia, and to estimate the rate of EP disappearance, we studied EP concentration, measured by double-antibody radioimmunoassay, in cord venous plasma and in serum at a mean age of 8 hours in a control group (n = 9) and in three patient groups: (1) infants with polycythemia (n = 10), (2) infants born to mothers with preeclampsia of pregnancy, without (n = 22) or with (n = 11) acidosis at birth, and (3) infants with acute birth asphyxia (n = 19), seven of whom had postnatal hypoxia. In all patient groups, cord venous EP was elevated in comparison with values in control infants. No change was found in EP level between birth and 8 hours in control infants (geometric mean in cord and 8-hour sample: 20 and 16 mU/ml, not significant) or in acutely asphyxiated infants with postnatal hypoxia (122 and 72 mU/ml, not significant), whereas the EP level decreased in all other groups: infants with polycythemia (123 to 24 mU/ml, p less than 0.001), nonacidotic infants (78 to 26 mU/ml, p less than 0.001) and acidotic infants (176 to 38 mU/ml, p less than 0.001) of the preeclampsia group, and acutely asphyxiated infants without postnatal hypoxia (58 to 30 mU/ml, p less than 0.001). The mean (+/- SD) half-time of EP disappearance was 2.6 +/- 0.5 hours in infants with polycythemia and 3.7 +/- 0.9 hours in infants of the preeclampsia group.

Topics: Acidosis; Apgar Score; Asphyxia Neonatorum; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Polycythemia; Pre-Eclampsia; Pregnancy; Time Factors

Acute hypoxemia was produced in chronically catheterized sheep fetuses to determine the response time necessary to increase plasma immunoreactive erythropoietin (Ep) concentration. Sodium nitrite (0.2 mM) was infused via a fetal vein to induce fetal hypoxemia. The resultant fetal methemoglobinemia was associated with a predictable, incremental decrease in arterial oxygen content. Twelve nitrite infusions were performed in eight fetal sheep preparations (gestational ages 115-146 days). Mean methemoglobin level increased to 33% of total Hb after 1-2 h of NaNO2 infusion. These results were compared to those obtained in nine control studies in eight fetuses in which no change was observed for plasma Ep, arterial oxygen content, PaO2, pHa, or whole blood lactate. In the nitrite infused group, however, a significant and progressive increase in mean plasma Ep level over baseline levels was observed during the 4th and 5th h of hypoxemia (p less than 0.01). This change in Ep was significantly greater compared to the control group. These results, however, were confounded by the concomitant development of a lactic acidemia secondary to the fetal hypoxemia. To examine the theoretic possibility that lactic acidemia may primarily affect fetal Ep levels, an additional group of five fetuses was infused with L-lactic acid for the same time period. Although the decrements in pHa and whole blood lactate levels achieved in these fetuses were in excess of those observed during the nitrite infusions, this possibility was ruled out since no change in fetal plasma Ep levels occurred. We conclude that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis; Animals; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Hemodynamics; Lactates; Lactic Acid; Methemoglobinemia; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Sodium Nitrite

Topics: Acidosis; Animals; Blood Gas Analysis; Electric Stimulation; Erythropoietin; Hemoglobins; Hypercapnia; Hypoxia; Iron; Kidney; Male; Oxygen Consumption; Protein Binding; Rabbits

Topics: Acid-Base Equilibrium; Acidosis; Animals; Bicarbonates; Biological Transport, Active; Body Fluids; Carbon Dioxide; Colorado; Congresses as Topic; Erythrocytes; Erythropoietin; Glycerophosphates; Humans; Hydrogen-Ion Concentration; Hypoxia; Oxygen; Oxygen Consumption; Pulmonary Emphysema