losartan-potassium and Heart-Diseases

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

Topics: Algorithms; Anemia, Iron-Deficiency; Critical Care; Erythropoiesis; Erythropoietin; Female; Ferritins; Heart Diseases; Hematology; Humans; Iron; Male; Neoplasms; Pregnancy; Pregnancy Complications, Hematologic; Quality of Life; Respiration Disorders; Treatment Outcome

Advances in cancer treatment have greatly improved survival rates of children with cancer. However, these same chemotherapeutic or radiologic treatments may result in long-term health consequences. Anthracyclines, chemotherapeutic drugs commonly used to treat children with cancer, are known to be cardiotoxic, but the mechanism by which they induce cardiac damage is still not fully understood. A higher cumulative anthracycline dose and a younger age of diagnosis are only a few of the many risk factors that identify the children at increased risk of developing cardiotoxicity. While cardiotoxicity can develop at anytime, starting from treatment initiation and well into adulthood, identifying the best cardioprotective measures to minimize the long-term damage caused by anthracyclines in children is imperative. Dexrazoxane is the only known agent to date, that is associated with less cardiac dysfunction, without reducing the oncologic efficacy of the anthracycline doxorubicin in children. Given the serious long-term health consequences of cancer treatments on survivors of childhood cancers, it is essential to investigate new approaches to improving the safety of cancer treatments.

Topics: Adiponectin; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Carbazoles; Cardiolipins; Cardiotonic Agents; Carvedilol; Doxorubicin; Erythropoietin; Heart; Heart Diseases; Humans; Lipid Peroxidation; Liposomes; Neoplasms; Piperazines; Propanolamines; Purines; Razoxane; Risk Factors; Sildenafil Citrate; Sulfones; Survivors; Ventricular Dysfunction, Left

Posttransplantation anemia (PTA) is a prevalent sequela of solid organ transplantation and a potential independent risk factor for cardiovascular morbidity and mortality in kidney transplant recipients. There are multiple causes of PTA, some of which are associated with early phase anemia (<6 months), whereas others more often induce anemia in the late posttransplant phase (>6 months). Although impaired kidney function contributes to PTA, it is only one of many factors that result in anemia in transplant recipients. Other causes include iron deficiency, medications, infections, acute rejection, inflammation, and erythropoietin deficiency. Unlike in the predialysis chronic kidney disease population, the impact of anemia after kidney transplantation outcomes is unknown. This is in large part due to the absence of controlled trials that address whether correction of anemia improves allograft function or patient morbidity and mortality. Current guidelines recommend evaluation for hemoglobin level of less than 12 g/dL and treatment when the value falls less than 11 g/dL and a target of 11 to 12 g/dL. Additional treatments may entail removing the cause of the anemia, nutritional supplementation, and/or an erythrocyte stimulating agent.

Topics: Anemia; Cohort Studies; Erythropoietin; Heart Diseases; Hemoglobins; Humans; Incidence; Liver Transplantation; Lung Transplantation; Organ Transplantation; Prevalence; Quality of Life; Recombinant Proteins

Anemia has been identified as an independent prognostic factor of both morbidity and mortality for patients with congestive heart failure (CHF). The association between anemia and adverse outcomes has raised the hypothesis that anemia correction might lead to an improvement in the prognosis of patients with CHF. Nevertheless, data from large randomized trials about the effect of anemia correction on patient outcome are still lacking. Numerous clinical studies, randomized and nonrandomized, have evaluated the efficacy of erythropoietin or iron supplementation for treating anemia in patients with CHF, and their effect on patient symptoms and functional status. The superiority of any of these approaches has not been established yet. This review will discuss different treatment options for anemic patients with CHF, with emphasis on the correction of iron deficiency.

Topics: Anemia, Iron-Deficiency; Dietary Supplements; Erythropoietin; Heart Diseases; Humans; Iron, Dietary; Randomized Controlled Trials as Topic; Risk Factors

Bloodless surgery programs are being instituted because of increasing public concerns about blood transfusions and the need to accommodate some patients' religious beliefs. Patients' desires to forego transfusion must be identified during the preoperative screening process and subsequently reflected on the surgical consent. Patients are managed preoperatively with erythropoietin and dietary supplements. The surgical team employs a variety of intraoperative and postoperative blood conservation techniques to help avoid the need for transfusion. A retrospective review of congenital cardiac procedures in a blood conservation program confirmed that bloodless cardiac surgery is effective.

Topics: Blood Loss, Surgical; Blood Transfusion; Child, Preschool; Christianity; Epoetin Alfa; Erythropoietin; Heart Diseases; Hematinics; Humans; Infant; Perioperative Nursing; Recombinant Proteins; Retrospective Studies

The biology of iron in relation to anemia is best understood by a review of the iron cycle, since the majority of iron for erythropoiesis is provided by iron recovered from senescent erythrocytes. In iron-deficiency anemia, storage iron declines until iron delivery to the bone marrow is insufficient for erythropoiesis. This can be monitored with clinical indicators, beginning with low plasma ferritin, followed by decreased plasma iron and transferrin saturation, and culminating in red blood cells with low-Hb content. When adequate dietary iron is provided, these markers show return to normal, indicating a response to the dietary supplement. Anemia of inflammation (also known as anemia of chronic disease, or ACD) follows a different course, because in this form of anemia storage iron is often abundant but not available for erythropoiesis. The diagnosis of ACD is more difficult than the diagnosis of iron-deficiency anemia, and often the first identified symptom is the failure to show a response to a dietary iron supplement. Confirmation of ACD is best obtained from elevated markers of inflammation. The treatment of ACD, which typically employs erythropoietin (EPO) supplements and intravenous iron (i.v.-iron), is empirical and often falls shorts of therapeutic goals. Dialysis patients show a complex pattern of anemia, which results from inadequate EPO production by the kidney, inflammation, changes in nutrition, and blood losses during treatment. EPO and i.v.-iron are the mainstays of treatment. Patients with heart failure can be anemic, with incidence as high as 50%. The causes are multifactorial; inflammation now appears to be the primary cause of this form of anemia, with contributions from increased plasma volume, effects of drug therapy, and other complications of heart disease. Discerning the mechanisms of anemia for the heart failure patient may aid rational therapy in each case.

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Heart Diseases; Hematinics; Humans; Inflammation; Iron; Kidney Diseases; Male; Recombinant Proteins

Erythropoietin is a haematopoietic hormone with extensive non-haematopoietic effects. The discovery of an erythropoietin receptor outside the haematopoietic system has fuelled the research into the beneficial effects of erythropoietin for various conditions, predominantly in cardiovascular disease. Experimental evidence has revealed the cytoprotective and angiogenic properties of erythropoietin and it seems that the erythropoietin-erythropoietin receptor system provides a powerful backbone against acute and chronic myocardial ischemia, each gaining from the different properties of erythropoietin. Clinical trials in which erythropoietin was titrated to achieve certain haematocrit levels have generated equivocal results. It has been suggested that a (too) high haematocrit is undesirable in cardiovascular disease. We have shown that intermittent (low-dose) erythropoietin administration, that does not increase haematocrit substantially, suffices to activate the beneficial downstream pathways of erythropoietin. We postulate that intermittent administration or a lower than conventional dose of erythropoietin, not only aimed at increasing haemoglobin at high levels, will provide powerful cellular protection and will improve cardiac outcome, without the side effects of erythropoietin associated with increased haematocrit.

Topics: Animals; Cardiovascular Physiological Phenomena; Chronic Disease; Erythropoietin; Heart Diseases; Heart Failure; Humans; Receptors, Erythropoietin; Recombinant Proteins

In numerous studies, erythropoietin (EP) has been shown to be a "universal" protective tissue cytokine, and EP receptors have been shown to exist in a lot of tissues. The pleiotropic effects of EP (the anti-inflammatory effect, angiogenesis, anti-apoptosis etc.) make clinical application of EP (especially recombinant EP, REP, and EP analogs without erythropoietic activity) promising in different diseases. Possibilities provided by REP application in neurology, cardiology, hematology, oncology, and other clinical areas are being studied intensively. Clinical studies of EP are now solitary, and they should be continued; new EP analogs with specified qualities and selective mechanisms of action should be developed. This review discusses the modern state of EP investigation and possibilities provided by its clinical application.

Topics: Erythropoietin; Heart Diseases; Humans; Recombinant Proteins; Treatment Outcome

Anemia is a common finding in diabetes, particularly in patients with albuminuria or renal impairment. We recently showed that at least 1 in 5 outpatients with type 1 or type 2 diabetes in tertiary clinics have anemia, in whom it constitutes a significant additional burden. Anemia is associated strongly with an increased risk of diabetic complications including nephropathy, retinopathy, and heart failure. Although a number of factors contribute to an increased prevalence of anemia in diabetes, an uncoupling of hemoglobin concentration and renal erythropoietin synthesis associated with tubular dysfunction appears to be the dominant factor. In our patients with diabetes and anemia, more than three quarters had functional erythropoietin deficiency. This association was most pronounced in patients with renal impairment, in whom nearly half of all patients had anemia. However, 70% of anemic patients without renal impairment also had inappropriately low erythropoietin levels. Consequently, the likelihood of functional erythropoietin deficiency, as a cause of anemia in patients with diabetes, is not dependent on the severity of renal impairment. Although there is a clear rationale for correction of anemia in diabetes, it remains to be established whether this will lead to improved outcomes. Some small studies suggest improvement in cardiac outcomes and hospitalization. It is anticipated that large ongoing studies will help define the optimal approach to the management of anemia in diabetes.

Topics: Anemia; Diabetes Complications; Diabetic Angiopathies; Diabetic Nephropathies; Erythropoietin; Heart Diseases; Humans

Anemia, defined as a hemoglobin level of less than 12 g/dL, often is seen in congestive heart failure (CHF). It is associated with an increased mortality and morbidity and increased hospitalizations. Compared with nonanemic patients the presence of anemia also is associated with worse cardiac clinical status, more severe systolic and diastolic dysfunction, a higher beta natriuretic peptide level, increased extracellular and plasma volume, a more rapid deterioration of renal function, a lower quality of life, and increased medical costs. The only way to determine if anemia is merely a marker for more severe CHF or actually is contributing to the worsening of the CHF is to correct the anemia and see if this favorably influences the CHF. In several controlled and uncontrolled studies, correction of the anemia with subcutaneous erythropoietin (EPO) or darbepoetin in conjunction with oral and intravenous iron has been associated with an improvement in clinical status, number of hospitalizations, cardiac and renal function, and quality of life. However, larger, randomized, double-blind, controlled studies still are needed to verify these initial observations. The effect of EPO may be related partly to its nonhematologic functions including neovascularization; prevention of apoptosis of endothelial, myocardial, cerebral, and renal cells; increase in endothelial progenitor cells; and anti-inflammatory and antioxidant effects. Anemia also may play a role in increasing cardiovascular morbidity in chronic kidney insufficiency, diabetes, renal transplantation, asymptomatic left ventricular dysfunction, left ventricular hypertrophy, acute coronary syndromes including myocardial infarction and chronic coronary heart disease, and in cardiac surgery. Again, controlled studies of correction of anemia are needed to assess its importance in these conditions. The anemia in CHF mainly is caused by a combination of renal failure and CHF-induced increased cytokine production, and these can both lead to reduced production of EPO, resistance of the bone marrow to EPO stimulation, and to cytokine-induced iron-deficiency anemia caused by reduced intestinal absorption of iron and reduced release of iron from iron stores. The use of angiotensin-converting enzyme inhibitor and angiotensin receptor blockers also may inhibit the bone marrow response to EPO. Hemodilution caused by CHF also may cause a low hemoglobin level. Renal failure, cardiac failure, and anemia therefore all interact

Topics: Anemia; Animals; Attitude; Cardiology; Erythropoietin; Heart Diseases; Heart Failure; Hemoglobins; Humans; Internal Medicine; Iron; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Nephrology; Recombinant Proteins

Anemia has recently been recognized as a frequent complication of diabetic nephropathy, appearing earlier than in nondiabetic renal disease and amplifying the risks of cardiovascular and microvascular complications. A major cause is an inappropriate erythropoietin response to anemia, often accompanied by iron deficiency and therapy with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

Topics: Anemia; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Disease Progression; Erythropoietin; Heart Diseases; Humans

Anaemia is common in severe cardiac failure due to systolic dysfunction. The mechanisms are varied. Anaemia is a negative prognostic factor. Treatment with erythropoietin seems to improve the quality of life, functional status, effort tolerance and systolic function of these patients. Large scale clinical trials are on-going.

Topics: Anemia; Erythropoietin; Heart Diseases; Heart Failure; Humans; Recombinant Proteins

A neurohumoral link between kidneys and the heart has been established, particularly in the context of hypertension and cardiomyopathy. Beyond this neuro-endocrine pathway, another connecting system theoretically recruits growth factors that are selectively produced by the kidneys and have the ability to promote a distant reaction at the level of bone marrow. This reaction differentiates and circulates vascular progenitor cells capable of repairing the injured cardiovascular system. Reducing injuries (prevention) stabilizes disease processes by reducing tissue damage and destruction but the gradual degradation of the body's natural repair mechanisms eventually allows progressive reactivation of disease processes. In this light, a focus on tissue repair rather than injury prevention may hold the key to controlling chronic heart diseases. This article examines the medical therapies, including recombinant human erythropoietin, that have been shown to improve the function and survival of endothelial progenitor cells and promote the healing of damaged tissue.

Topics: Endothelium, Vascular; Erythropoietin; Growth Substances; Heart Diseases; Homeostasis; Humans; Inflammation; Kidney Failure, Chronic; Stem Cells

Cardiac disease represents a major cause of morbidity and mortality in dialysis patients, and is also a well-established feature of chronic kidney disease (CKD). Anaemia has also been shown to be a key component not only of dialysis and CKD but also of cardiac disease, including congestive heart failure (CHF). Furthermore, published clinical and laboratory data suggest that anaemia, CHF and CKD are interrelated, each causing the other to worsen and thus resulting in a 'vicious cycle' of disease progression which we have called the Cardio-Renal Anaemia syndrome. In this syndrome anaemia may cause CKD or be caused by CKD, anaemia may cause CHF or be caused by CHF and CHF may cause CKD or be caused by CKD. Numerous publications have borne out the fact that anaemia correction through epoetin treatment provides great benefit to CKD patients. Additionally, there is evidence to suggest that these benefits may be extended to patients with cardiac disease. Uncontrolled and controlled studies of the effect of subcutaneous epoetin treatment in anaemic patients with both CHF and CKD show significant improvements in both cardiac and renal function. Despite these findings, however, it is apparent that anaemia correction is not implemented rigorously within both CHF and CKD populations. Greater awareness of the need for early anaemia correction therapy is therefore required. Cooperation between nephrologists and others who are caring for CHF patients, especially cardiologists, is crucial.

Topics: Anemia; Erythropoietin; Heart Diseases; Humans; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

The importance of iron in the manufacture of erythrocytes is self-evident. In recent years, the treatment of anaemia of end-stage renal disease with recombinant human erythropoietin (epoetin) has been optimized by adequate iron supply. Intravenous therapy with dextran-free iron compounds has become the ideal and necessary companion of epoetin therapy. Anxiety has been expressed by clinicians and researchers over the impact of excess levels of iron following i.v. administration. Their concerns have included the potential for short-term side effects such as anaphylactic reactions and response to 'free iron'. Long-term concerns have included the possibility of increased infection, oxidative stress and cardiovascular disease with higher levels of iron. The literature also implies that i.v. iron could be a 'two-edged sword', i.e. on the one hand, it optimizes epoetin therapy, while on the other, it puts the patient at greater risk of other complications. This review assesses the evidence for these concerns and concludes that i.v. therapy with dextran-free iron compounds, such as iron sucrose, optimizes epoetin therapy with no direct evidence of any short-term or long-term complications.

Topics: Anemia; Chemotherapy, Adjuvant; Drug Hypersensitivity; Erythropoietin; Ferritins; Heart Diseases; Hematinics; Humans; Infections; Infusions, Intravenous; Iron Compounds; Kidney Failure, Chronic; Oxidative Stress; Recombinant Proteins

The optimal hematocrit target range in children with end-stage renal disease, who are receiving recombinant human erythropoietin, is ambiguous due to the lack of compelling, age-appropriate studies. There are a large number of adult and pediatric studies which show that physical performance as well as morbidity and mortality are positively influenced by partial normalization of the hematocrit to 30 vol% to 36 vol%. Cognition studies performed in adults similarly show improvement with partial correction of hematocrit. Normalization of hematocrit studies show lower mortality rates, incremental further improvement in cognition, and greater resolution of cardiac anomalies when compared with patients with partial correction of anemia. Conversely, cardiac death rates may increase in adult patients receiving hemodialysis with preexisting cardiac disease, and there are concerns about the effect of recombinant human erythropoietin on catheter/shunt/fistula patency and on blood pressure. The high cost of recombinant human erythropoietin and established Medicare and Dialysis Outcomes Quality Initiative target hematocrit ranges have also influenced pediatric nephrologists in their assessment of the risk-benefit ratios, despite new adult data suggesting that maintenance of higher hematocrits may be cost-effective. The rationale of using adult-derived hematocrits in children with end-stage renal disease needs to be re-examined in the context of the unique growth and developmental requirements of children. A prospective, multicenter study which determines the relative benefits and risks of age-adjusted hematocrit normalization in children with renal failure is warranted.

Topics: Anemia; Child; Cognition; Erythropoietin; Heart; Heart Diseases; Hematocrit; Humans; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; Renal Dialysis

Topics: Adult; Aged; Blood Banks; Blood Transfusion, Autologous; Child; Clinical Trials as Topic; Contraindications; Cost-Benefit Analysis; Erythropoietin; Female; Heart Diseases; Humans; Infection Control; Patient Selection; Pregnancy; Pregnancy Complications; Preoperative Care

Topics: Altitude; Biological Transport; Chronic Disease; Erythropoietin; Heart Diseases; Hemoglobins, Abnormal; Humans; Hypoxia; Lung Diseases; Lung Diseases, Obstructive; Oxygen; Oxygen Consumption; Polycythemia

Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome.. In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289.. Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group.. An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery.. Vifor Pharma and Swiss Foundation for Anaesthesia Research.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cardiac Surgical Procedures; Double-Blind Method; Drug Therapy, Combination; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Folic Acid; Heart Diseases; Humans; Male; Maltose; Middle Aged; Preoperative Care; Prospective Studies; Time Factors; Vitamin B 12

The Normal Hematocrit Trial (NHT) was the largest trial of epoetin randomizing 1265 hemodialysis patients with cardiac disease to lower (9-11 g/dl) or higher (13-15 g/dl) hemoglobin (Hgb), hypothesizing that higher Hgb would reduce mortality, and improve survival and quality of life. The trial was terminated early, and a 1998 publication reported that targeting higher hematocrit levels led to an insignificant increase in the primary end points (death or myocardial infarct), or risk ratio 1.3, 95% confidence interval (CI), 0.9-1.90, but the P-value was not given, and all-cause death risk was not reported. A higher target reportedly did not increase hospitalization rates, but did significantly improve the 'physical function' domain of quality of life. Comparing the 1996 Food and Drug Administration (FDA)-filed clinical trial report to the 1998 publication, however, found several discrepancies. Among these, the 1998 article reported interim trial results with only the adjusted CI but did not state that the unadjusted CIs were 99.912th percentile, and despite being a secondary end point, reported only the association of achieved Hgb with higher quality of life score. Randomization to the higher target had actually increased the risk for the primary end point (risk ratio 1.28, 95% CI=1.06-1.56; P=0.0112; 99.92% CI=0.92-1.78), the risk of death (risk ratio 1.27, 95% CI=1.04-1.54), non-access thrombotic events (P=0.041), and hospitalization rate (P=0.04), while 'physical function' did not improve (P=0.88). Hence, disclosure of these results in the 1998 publication or access to the FDA-filed report on the NHT in the late 1990s would likely have led to earlier concerns about epoetin safety and greater doubts about its benefits.

Topics: Access to Information; Anemia; Biomarkers; Chi-Square Distribution; Early Termination of Clinical Trials; Emotions; Erythropoietin; Evidence-Based Medicine; Health Status; Heart Diseases; Hematinics; Hematocrit; Hemoglobins; Hospitalization; Humans; Kaplan-Meier Estimate; Kidney Diseases; Mental Health; Patient Safety; Practice Guidelines as Topic; Predictive Value of Tests; Proportional Hazards Models; Quality of Life; Renal Dialysis; Risk Assessment; Risk Factors; Social Behavior; Time Factors; Treatment Outcome; United States

It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m2, respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus -2.31; P = 0.036). Overall adverse event rates were similar in both target groups; higher (P < 0.05) rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events were seen in the higher target group. Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure, compared with partial correction.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Heart Diseases; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Hypertension is a recognized complication of partial correction of anemia with recombinant human erythropoietin (epoetin) in hemodialysis patients. We used interdialytic ambulatory blood pressure (ABP) monitoring to study the effects of partially corrected anemia versus normal hematocrit (hct) on BP in hemodialysis patients.. Repeated interdialytic ABP monitoring was performed for up to one year in 28 chronic hemodialysis patients with cardiac disease who were randomized to achieve and maintain normal hct levels (42 +/- 3%, group A) or anemic hct levels (30 +/- 3%, group B) with epoetin. Routine BP measurements obtained at dialysis treatments were also evaluated.. Mean hct levels were 30.7 +/- 0.7% in group A and 30.6 +/- 0.7% in group B at baseline, then 39.3 +/- 1.2% (group A) and 33.5 +/- 0.6% (group B) at four months, and 42.0 +/- 1.1% (group A) and 30.4 +/- 1.0% (group B) at 12 months. Baseline ABP and routine dialysis unit BP levels were not different between the groups. At 2, 4, 8, and 12 months of follow-up, there were no statistically significant differences in any BP parameters between groups or increases in any BP parameters in either group A or group B patients compared with baseline. At 12 months, the mean nighttime diastolic BP (DBP) in group A patients was slightly but significantly lower than the mean daytime DBP (daytime DBP 76.6 +/- 1.9 mm Hg vs. nighttime DBP 72.9 +/- 2.1 mm Hg, P < 0.05). The mean daytime and nighttime BPs were not different from each other at two, four, and eight months in group A or at any time in group B, and in both groups, most patients had little diurnal change in BP.. Correction of hct to normal with epoetin in chronic hemodialysis patients with cardiac disease did not cause increased BP as assessed by interdialytic ABP monitoring or by the measurement of routine predialysis and postdialysis BP. There was little diurnal change in systolic or diastolic BP at baseline or after correction of anemia to normal levels, and although mean nighttime DBP was lower than mean daytime DBP at 12 months in group A, the maintenance of normal hct levels did not affect the abnormal diurnal BP pattern seen at moderately anemic hct levels in most patients.

Topics: Aged; Anemia; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Diastole; Erythropoietin; Female; Heart Diseases; Hematocrit; Humans; Male; Middle Aged; Recombinant Proteins; Reference Values; Renal Dialysis

Objectives To investigate mechanisms of in utero death in normally formed fetuses by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]), myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary acidic protein [GFAP]), correlated with risk factors for fetal death and placental histopathology. Methods This retrospective, observational cohort study included intrauterine deaths with transabdominal amniocentesis prior to induction of labor. Women with a normal pregnancy and an indicated amniocentesis at term were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using commercial immunoassays. Placental histopathology was reviewed, and CD15-immunohistochemistry was used. Analyte concentrations >90th centile for controls were considered "raised". Raised AF EPO, AF cTnI and AF GFAP concentrations were considered evidence of hypoxia, myocardial and brain injury, respectively. Results There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60), myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths. Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77% (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological evidence for placental dysfunction was found in 74% (43/58) of these cases. Conclusion Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be caused by cardiac arrhythmia secondary to a cardiac conduction defect.

Topics: Adult; Amniocentesis; Amniotic Fluid; Brain Injuries; Cause of Death; Erythropoietin; Female; Fetal Death; Fetal Diseases; Fetal Hypoxia; Glial Fibrillary Acidic Protein; Heart Diseases; Humans; Immunohistochemistry; Placenta; Pregnancy; Random Allocation; Retrospective Studies; Stillbirth; Troponin I; United States

Heart surgery patients have a high prevalence of anemia. Its etiology is multifactorial, and iron deficiency is one of the most common correctable causes. Anemia is an independent risk factor for postsurgical morbidity and mortality. It also predisposes patients to a greater need for transfusions, which increases the associated complications and the use of resources. The etiological diagnosis of anemia is no different from that of other surgical procedures, but the time available for correcting it before surgery is shorter. Studies have been conducted on therapeutic regimens with iron deficiency replenishment with total dose and erythropoiesis-stimulating agents, which enable the rapid correction of anemia and reduce transfusion requirements. There is considerable variability in terms of dosage, adverse effects, administration time and routes, drug combinations and results. New studies are needed to investigate the most ideal regimens for correcting anemia in these patients.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Clinical Trials as Topic; Erythropoietin; Heart Diseases; Hematinics; Hemoglobins; Humans; Iron; Medical Errors; Multicenter Studies as Topic; Observational Studies as Topic; Preoperative Care; Prevalence; Recombinant Proteins; Risk Factors

Doxorubicin (DOX) is a highly effective anti-cancer drug with limited clinical use due to its serious cardiotoxicity. Recent studies reported that erythropoietin (EPO) could exert a cardioprotective effect by non-erythropoietic effects. This study was to investigate fibrosis of DOX-induced cardiotoxicity and determine mechanisms of EPO against extracellular matrix (ECM) remodelling.. Rats were grouped as the control group, the DOX group and the DOX+EPO group. DOX (2.5 mg/kg/dose, six doses for two weeks) was administered to induce cardiotoxicity by intraperitoneal injections in the DOX group and the DOX+EPO group, and EPO (2500U/kg/dose, six doses for two weeks) was administered simultaneously in the DOX+EPO group. Two weeks after the last administration, rats were killed with cardiac tissues used for histological analyses and immunological detections for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2).. Rats treated with DOX showed degenerative changes with cardiac fibrosis. Compared to the control group, the expression of MMP-2 was up-regulated whereas that of TIMP-2 was down-regulated in the DOX group. EPO administration improved cardiac fibrosis, decreased MMP-2 expression, increased TIMP-2 expression and ameliorated imbalance of MMP-2/TIMP-2 ratio.. The present study suggests that EPO can exert a cardioprotective effect on DOX-induced cardiotoxicity which may be associated with improving MMP-2/TIMP-2 imbalance.

Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxins; Down-Regulation; Doxorubicin; Erythropoietin; Fibrosis; Heart Diseases; Male; Matrix Metalloproteinase 2; Rats; Rats, Wistar; Time Factors; Tissue Inhibitor of Metalloproteinase-2; Up-Regulation

Patients with chronic kidney disease (CKD) frequently suffer from heart disease as well. The combination of the two processes can exacerbate inflammation, resulting in increases in both resistance to erythropoietin (EPO) and mortality.. The aim of this study was to determine the prevalence of heart disease in a representative group of non-dialysis patients with stage 4-5 CKD, and the influence of that entity on EPO requirements and on mortality during a period of 36 months.. 134 patients (68% on EPO at the beginning, increasing to 72.3% during follow-up) were monitored for 36 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI) calculated as the weekly weight-adjusted dose of EPO divided by the haemoglobin level. The ERI was determined both initially and during the last six months before the end of the study.. 39 patients (29.1%) had history of heart disease; 22 (16.4%) had suffered from heart failure (HF). The ERI was higher in patients with a history of heart disease or HF and those treated with drugs acting on the renin-angiotensin system (ACE inhibitors or ARBs). Using ERI as the dependent variable in the multivariate analysis, the variables that composed the final model were ferritin, haemoglobin, glomerular filtration rate and history of HF. The 36 month mortality rate (n=39 patients) was higher in the group having ERI above the median (2.6IU/week/kg/gram of haemoglobin in 100ml) (P=.002), and in the groups with heart disease (P=.001) or HF (P=.001) according to the Kaplan-Meier survival analysis.. Patients with history of heart disease or HF have a higher ERI, and all of these characteristics are associated with lower survival. ERI can be considered a marker for risk of death in the short to-medium term.

Topics: Aged; Aged, 80 and over; Anemia; Autoimmune Diseases; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Heart Diseases; Heart Failure; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Severity of Illness Index

The Normal Hematocrit Cardiac Trial, published in 1998, was a foundational study testing erythropoietin analog treatment to normal hematocrit targets. It served as a warning that erythropoietin replacement was not a panacea. Its large size gave it disproportionate weighting in evidence reviews and guideline development and thereby impacted treatment decisions. Coyne shows that the published results did not completely and clearly represent the study's actual results. We discuss the implications and make recommendations to prevent such occurrences.

Topics: Anemia; Erythropoietin; Heart Diseases; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Diseases; Quality of Life; Renal Dialysis

Topics: Anemia; Erythropoietin; Heart Diseases; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Diseases; Quality of Life; Renal Dialysis

New perspectives have emerged regarding the processes associated with depressive disorders and their many comorbid conditions. Particular attention has been paid to the potential role of inflammatory factors in promoting these illnesses. These inflammatory responses include those elicited by pathogenic stimuli, as well as sterile inflammatory processes, such as those related to severe or chronic stress. These diverse challenges may activate common processes in which cytokines, which are inflammatory signaling molecules, provoke the dysregulation of several growth factors, including brain-derived neurotrophic factor, fibroblast growth factor-2, macrophage migration inhibitory factor, and erythropoietin. The result of such dysregulation favors the development of depressive disorders and their comorbid illnesses, such as heart disease, diabetes, autoimmune conditions, and poststroke depression.

Topics: Animals; Brain-Derived Neurotrophic Factor; Comorbidity; Cytokines; Depressive Disorder; Diabetes Mellitus; Erythropoietin; Fibroblast Growth Factor 2; Heart Diseases; Humans; Inflammation Mediators; Interleukin-6; Macrophage Migration-Inhibitory Factors; Models, Biological; Models, Psychological; Signal Transduction; Stress, Psychological; Tumor Necrosis Factor-alpha

HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD.. The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD.. An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants.. HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.

Topics: Erythropoietin; Heart Diseases; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Infant; Infant, Newborn; Persistent Fetal Circulation Syndrome; Vascular Endothelial Growth Factor A

Nilotinib (Tasigna) is a second-generation BCR-ABL kinase inhibitor, recently introduced and used for the treatment of chronic or accelerated phase CML patients, intolerant or resistant to imatinib. This treatment represents and important step forward for the disease control of such patients but can lead to side effects, sometimes serious, which can limit its optimal use. We propose here some guidelines that might be of help in daily practice, in order to manage properly these side effects.

Topics: Antineoplastic Agents; Benzamides; Drug Eruptions; Drug Interactions; Drug Resistance, Neoplasm; Erythropoietin; Fertility; Food-Drug Interactions; France; Granulocyte Colony-Stimulating Factor; Heart Diseases; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Metabolic Diseases; Neutropenia; Piperazines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrimidines; Recombinant Proteins

Chronic kidney disease (CKD) patients develop anemia because of the low kidney erythropoietin (EPO) production, thus promoting cardiovascular complications. The degree of renal insufficiency might determine the moment to start recombinant human erythropoietin (rhEPO) therapy, but the molecular basis for these options deserves better elucidation. This study aimed to clarify the cardio-renal effects of earlier rhEPO therapy in rats with moderate chronic renal failure (CRF). Four groups of rats were evaluated for 15 weeks (control; rhEPO - 50 IU/kg/week; CRF - 3/4 nephrectomy; CRF + rhEPO) to assess renal and hematology data, EPO levels, blood pressure, heart rate, peripheral catecholamines contents, serum-transforming growth factor-β1 (TGF-β1), kidney gene expression of EPO, Caspase 9 (Casp9), and vascular endothelial growth factor (Vegf). This model of moderate CRF showed moderate and corrected anemia, hypertension, tachycardia, sympathetic overactivity, and increased serum TGF-β1 content. The remnant kidney showed a proliferative profile, with hypertrophy, downregulated gene expression of EPO, and upregulated gene expression of Vegf and Casp9. rhEPO treatment promoted erythrocytosis and prevented tachycardia and catecholamines increment, with a rise of serum TGF-β1. Furthermore, the decreased kidney gene expression of EPO and the overexpression of Casp9 were prevented, demonstrating a renoprotective action on the remnant kidney. In conclusion, rhEPO therapy promotes a protective effect on the cardio-renal axis, which might be mainly attributed to its pro-proliferative and anti-apoptotic properties. These findings might recommend its use in earlier stages of CRF, acting as an erythropoiesis stimulating agent, to efficiently correct not only the anemia, one of the major complications in these patients, but also the succeeding adverse cardio-renal effects.

Topics: Animals; Blood Pressure; Caspase 9; Disease Models, Animal; Erythropoietin; Heart Diseases; Heart Rate; Humans; Kidney; Kidney Function Tests; Male; Peripheral Nervous System; Rats; Rats, Wistar; Recombinant Proteins; Renal Insufficiency, Chronic; Sympathetic Nervous System; Vascular Endothelial Growth Factor A

Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly suppresses degradation of the alpha-subunit of hypoxia-inducible factor-1 (HIF-1), an activator of the gene encoding the cardioprotective cytokine erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1 blood-crystalloid cardioplegia. The crystalloid component contained 188 mM glucose + or - 24 mM pyruvate. After 30-min cardiac reperfusion with cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1alpha, EPO and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression, and increased HIF-1alpha, EPO, and EPO-R protein contents by 60, 58, and 123%, respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also increased ERK phosphorylation by 61 and 118%, respectively, vs. control cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell 32% following control CPB vs. sham, but pyruvate cardioplegia prevented these declines, yielding 49 and 80% greater NOS activity and eNOS content vs. respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced myocardial EPO expression and mobilized the EPO-ERK-eNOS mechanism. By stabilizing HIF-1alpha, pyruvate-fortified cardioplegia may evoke sustained activation of EPO's cardioprotective signaling cascade in myocardium.

Topics: Animals; Blood Pressure; Cardioplegic Solutions; Cardiopulmonary Bypass; Edema, Cardiac; Energy Metabolism; Erythropoietin; Extracellular Signal-Regulated MAP Kinases; Female; Glutathione; Heart Arrest, Induced; Heart Diseases; Heart Rate; Heart Ventricles; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Models, Animal; Myocardium; Nitric Oxide Synthase Type III; Oxidation-Reduction; Phosphorylation; Proto-Oncogene Proteins c-akt; Pyruvic Acid; Receptors, Erythropoietin; RNA, Messenger; Signal Transduction; Swine; Time Factors; Up-Regulation

Topics: Angiogenesis Inducing Agents; Animals; Cell Movement; Coronary Vessels; Darbepoetin alfa; Endothelial Cells; Erythropoietin; Heart Diseases; Humans; Myocardium; Neovascularization, Physiologic; Stem Cells; Ventricular Function, Left

The aim of this work was to investigate the effects of different recombinant human erythropoietin (rhEPO) doses on the infarction development and if rhEPO could protect against the deleterious consequences induced by a previous intermittent hypoxia (IH, FiO(2) 5%, 4h). First, isolated rat hearts were submitted to an ischemia-reperfusion. rhEPO was infused before or after ischemia, at different doses. Secondly, rats were exposed to of IH. Twenty-four hours later, hearts underwent the ischemia-reperfusion protocol. For some hearts, 5Uml(-1) rhEPO was infused as previously. We observed that rhEPO has a dose-dependant effect on infarct size since it was significantly reduced by rhEPO infusions before or after ischemia. We also showed that 4h of IH induced a higher sensitivity to the infarction which was prevented by rhEPO. In conclusion, rhEPO administration before or after ischemia can protect isolated rat myocardium in a dose dependent manner and efficiently prevents the higher sensitivity to the infarction induced by previous intermittent hypoxia.

Topics: Animals; Coronary Circulation; Erythropoietin; Heart Diseases; Heart Rate; Hypoxia; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Wistar; Recombinant Proteins; Ventricular Function, Left

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

Incidents of heart and renal failure (HF, RF) together, are increasing in our country and all over the world, so a great attention has been dedicated to this problem recently. These diseases together have shown bad results because of the process of accelerated arteriosclerosis, structural changes of myocardium, oxidative stress, inflammation, increased activities of sympathetic nervous system (SNS), increased activities of a renin-angiotensin-aldosterone system (RAAS) (1). These factors are crucial in the development of patho-physiological process and consequential development of anemia, that together with heart and renal failure through interaction, cause serious disorder that we call the cardio-renal anemia syndrome (2). We examined effects of erythropoietin (Epoetin beta) at 90 (60 men and 30 women) pre-dialysed and dialysed patients with HF signs during a period of three years in individual dozes of 2000-6000 units subcutaneous (sc) weekly. Using computer S PLUS and SAS multiple variant analysis we have got correlations by Pearson. Epoetin beta significantly develops anemia parameters: number of erythrocytes (r=0.51779; p<0.0001), hemoglobin (r=0.38811; p<0.0002), MCV (r=0.59876; p<0.0001) at patients with HF. Positive effects are seen at NYHA class (r=0.59906; p<0.0001), on quality of life before and after prescribing medicine. Parameters of renal functions are improving: more urea (r =0.45557; p<0.0001) than creatinine (r=0.26397; p<0.00119) and potassium values K(+)) are not changed significantly (r=0.02060; p<0.8471). Epoetin beta has been useful in treatment of pre-dialysed and dialysed patients with HF and anemia by improving functional ability of myocardium and quality of life.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Blood Glucose; Blood Urea Nitrogen; Creatinine; Cytokinins; Erythrocyte Count; Erythropoietin; Female; Heart Diseases; Hematopoiesis; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Malnutrition; Middle Aged; Potassium; Recombinant Proteins; Renal Dialysis; Syndrome; Tumor Necrosis Factor-alpha

Complex cardiac surgery often requires blood transfusion. Some patients refuse transfusion, even when it is potentially life-threatening to do so. Although recombinant human erythropoietin (rhEPO) has been used to reduce the need for blood transfusion, it has been considered ineffective in critically ill patients. The time course of hematological responses in a Jehovah's Witness patient with acute renal failure and severe cardiac disease suggests that a trial of rhEPO should be considered for salvage therapy in critically ill patients.. The authors describe successful treatment of life-threatening anemia using recombinant human erythropoietin in a critically ill Jehovah's Witness patient after cardiac surgery.

Topics: Acute Kidney Injury; Blood Cell Count; Cardiac Surgical Procedures; Critical Care; Critical Illness; Erythropoietin; Female; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Jehovah's Witnesses; Middle Aged; Recombinant Proteins

Topics: Anemia; Cardiovascular System; Erythropoietin; Heart Diseases; Humans; Uremia; Vascular Resistance

Topics: Comorbidity; Drug Resistance; Epoetin Alfa; Erythropoietin; Heart Diseases; Hematocrit; Humans; Recombinant Proteins; Renal Dialysis; Risk Factors

Topics: Epoetin Alfa; Erythropoietin; Extracellular Space; Heart Diseases; Hematocrit; Humans; Plasma Volume; Recombinant Proteins; Renal Dialysis

Topics: Base Sequence; Erythropoietin; Heart Diseases; Humans; Immunity, Cellular; Molecular Sequence Data; Polymerase Chain Reaction; Postoperative Period; Recombinant Proteins; T-Lymphocytes

The correction of renal anemia by recombinant human erythropoietin (rHuEPO) makes it possible to assess the effect of anemia on uremic cardiopathy (UC). So far, conflicting results have been reported. We studied 10 hemodialyzed patients aged (51 +/- 18 years, dialytic age 47 +/- 18 months) before and after rHuEPO treatment. All patients underwent an echocardiogram before, and six months after stable hematocrit (31 +/- 2) was obtained. The results show a reduction in LVDD. No improvement in ejection fraction and in ventricular hypertrophy was observed, probably owing to an increase in blood pressure. Finally, there is a possibility that the myocardium of hemodialyzed patients undergoes anatomical changes which may not improve, even after anemia correction.

Topics: Adult; Aged; Anemia; Erythropoietin; Female; Heart Diseases; Humans; Male; Middle Aged; Recombinant Proteins; Uremia; Ventricular Function

The change of cell-mediated immunity was studied in patients receiving open heart surgery with or without administration of recombinant erythropoietin (rEPO). Group I was not administered rEPO in 30 patients, and Group II was done intravenously with 200U/kg/day of rEPO for 6.4 +/- 2.4 days before operation and also for 7.2 +/- 3.6 days after operation in 20 patients. The ratio of reticulocyte increased in all patients receiving rEPO. In both groups the ratios of OKT3 and OKT4 positive T lymphocytes decreased significantly on postoperative day 1. However, the ratios in patients with rEPO increased more significantly than in those without rEPO. Lymphocyte blast formation which was indicated by PHA-SI (phytohemagglutinin stimulation index) increased after administration of rEPO. The postoperative PHA-SI in both groups showed similar changes. The level of interleukin-2 (IL-2) production increased after the administration similar to PHA-SI change. The level of it decreased on postoperative day 1 and increased on postoperative days 3 and 7. We administered 200U/kg/day of rEPO for 7 days in a patient with postoperative erythroderma after open heart surgery and the level of IL-2 production was found to also increase in patient according with recovery of symptom. In conclusion, our data suggested that the rEPO might effect on not only erythrocyte but also lymphocyte activation.

Topics: Adult; Aged; Dermatitis, Exfoliative; Erythrocyte Count; Erythropoietin; Heart Diseases; Humans; Immunity, Cellular; Interleukin-2; Lymphocyte Activation; Male; Middle Aged; Postoperative Complications; Recombinant Proteins; Reticulocytes

Recombinant human erythropoietin (rHuEPO) was administered to 42 elective heart surgery patients, and the volume of autologous blood donated within the preoperative short period and effects of improving anemia by postoperative rHuEPO administration were studied. rHuEPO (100 U/kg/day) and chondroitin sulfate-iron (40 mg/day) were given intravenously for preoperative 14 days, and each 400 ml of autologous blood was donated on the 14th and 4th day before operation. Reticulocytes increased significantly 3 days after administration (p less than 0.01). The hemoglobin level, 13.4 +/- 1.0 g/dl before the first donation, returned to 13.4 +/- 1.1 g/dl just before operation. 800 ml of autologous blood, needed for usual open heart surgery, may possibly have been donated within 14 days without making patients anemic by intravenous rHuEPO administration. For postoperative rHuEPO administration, the patients were divided into 3 groups: Group I (10 cases): given for 14 days, Group II (12 cases): for 7 days, Group III (20 cases): no administration. Reticulocytes decreased rapidly after termination of rHuEPO administration in each group, and on the 7th day after termination, they returned to the level before administration. The hemoglobin level in Group I was maintained after termination of rHuEPO, and was +2.2 +/- 1.1 g/dl on the 21st postoperative day compared with the level of 1st postoperative day. The hemoglobin level in Group II fell after termination and was +0.9 +/- 0.7 g/dl on the 21st day, this being comparable to the level of Group III. There were significant differences between Group I and II (p less than 0.05), and between Group I and III (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Transfusion, Autologous; Blood Volume; Erythropoietin; Female; Heart Diseases; Humans; Male; Middle Aged; Postoperative Care; Preoperative Care; Recombinant Proteins

Topics: Adult; Christianity; Erythropoietin; Female; Heart Diseases; Humans; Middle Aged; Premedication; Recombinant Proteins; Religion and Medicine

We have used recombinant human erythropoietin (rEPO) in order to prevent patients from developing anemia following preoperative autologous blood preservation. Thereby, we have been able to reduce intraoperative homologous blood transfusion during cardiac operations. In June and July, 1989, six middle-aged selective patients received rEPO (200 IU/kg) intravenously every other day starting from fifteen days before the day of their operations. One unit (200 ml) of autologous blood was drawn and preserved every few days. However, no significant differences were observed in red cell counts, hematocrit, hemoglobin and serum protein levels between before and after preservation. Not only preoperative autologous blood preservation with provision of rEPO, but also using the intraoperative autotransfusion system enabled us to perform cardiac operations on 5 out of 6 patients without any homologous blood transfusion. None of the six patients exhibited any undesirable effects due to rEPO administration. Their postoperative courses were excellent.

Topics: Blood Preservation; Blood Transfusion; Blood Transfusion, Autologous; Erythropoietin; Female; Heart Diseases; Humans; Intraoperative Care; Male; Middle Aged; Recombinant Proteins

Atrial thrombosis is a common lesion in female Taconic Swiss mice fed a high-fat (28%), low-protein (8%), hypolipotropic diet for 10 wk or longer. After the third week of such feeding the mice studied here were injected with either erythropoietin, washed, packed red blood cells, lysed red blood cells, plasma or physiological saline.In mice receiving injections of lysed red cells, plasma or saline, respectively 75, 54 and 82% of those surviving for 10 wk had developed atrial thrombosis. Hematocrits were 9.3% or below in these groups. Hematocrits were maintained at an average of 33.0% in the erythropoietin group and 32.4% in the transfused (packed erythrocytes) group. Only one of the erythropoietin injected animals and none of the transfused animals developed atrial thrombosis. The evidence indicates that the anemia induced by the experimental diet results from lack of erythropoietin production or activity and that the hypoxia of anemia plays a role in the development of atrial thrombosis.

Topics: Anemia; Animals; Blood Transfusion; Body Weight; Diet; Dietary Fats; Erythrocytes; Erythropoietin; Female; Heart Atria; Heart Diseases; Hematocrit; Injections, Intraperitoneal; Mice; Plasma; Reticulocytes; Sodium Chloride; Thrombosis

Topics: Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Anemia, Myelophthisic; Anemia, Sickle Cell; Bone Marrow; Erythropoietin; Heart Diseases; Hematocrit; Humans; Hypoxia; Kidney Diseases; Reticulocytes; Spherocytosis, Hereditary