losartan-potassium and Coronary-Disease

Association between androgens and erythropoiesis has been known for more than seven decades. Androgens stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells. Before the discovery of recombinant erythropoietin (rhEpo), androgens were used in the treatment of anemia associated with renal disease, bone marrow suppression, and hypopituitarism. Anabolism is an additional advantage of androgen therapy. Furthermore, in light of recent reports regarding adverse effects of rhEpo, the role of androgen therapy in various types of anemias should be readdressed. Polycythemia remains a known side effect of androgen therapy. In this review, we will briefly discuss the initial animal and human studies which demonstrated the role of androgens in the treatment of anemia, their mechanism of action, a detailed account of the efficacy of androgens in the treatment of various anemias, the erythropoietic side effects of androgens and finally, the relationship between hematocrit levels and cardiovascular disease.

Topics: Aging; Androgens; Anemia; Anemia, Aplastic; Animals; Bone Marrow; Coronary Disease; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Male

Endothelial injury is thought to play a pivotal role in the development and progression of vascular diseases, such as atherosclerosis, hypertension or restenosis, as well as their complications, including myocardial infarction or stroke. Accumulating evidence suggests that bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. Coronary artery disease and its risk factors, such as diabetes, hypercholesterolemia, hypertension and smoking, are associated with a reduced number and impaired functional activity of circulating EPCs. Moreover, initial data suggest that reduced EPC levels are associated with endothelial dysfunction and an increased risk of cardiovascular events, compatible with the concept that impaired EPC-mediated vascular repair promotes progression of vascular disease. In this review we summarize recent data on the effects of pharmacological agents on mobilization and functional activity of EPCs. In particular, several experimental and clinical studies have suggested that statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, PPAR-gamma agonists and erythropoietin increase the number and functional activity of EPCs. The underlying mechanisms remain largely to be defined; however, they likely include activation of the PI3-kinase/Akt pathway and endothelial nitric oxide synthase, as well as inhibition of NAD(P)H oxidase activity of progenitor cells.

Topics: AC133 Antigen; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antigens, CD; Antigens, CD34; Atherosclerosis; Benzopyrans; Carbazoles; Cardiovascular Diseases; Carvedilol; Cell Differentiation; Coronary Disease; Endothelium, Vascular; Erythropoietin; Ethanolamines; Glycoproteins; Hematopoietic Stem Cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Insulin; Nebivolol; Neovascularization, Physiologic; Oxidative Stress; Peptides; PPAR gamma; Propanolamines; Receptors, Angiotensin; Regeneration; Risk Factors; Rosiglitazone; Stem Cells; Thiazolidinediones; Vasodilator Agents

Anemia is common among patients with coronary artery disease (CAD) and portends a higher risk of short- and long-term mortality, major adverse cardiac events, and bleeding complications. Blood transfusion has long been the cornerstone of therapy for anemia; however, its benefit in patients with CAD is controversial and the appropriate threshold for transfusion has been widely debated. In this review, we summarize the studies evaluating the impact of anemia in patients with CAD undergoing percutaneous coronary intervention and address several issues regarding the use of transfusion in anemic patients. In addition, we discuss alternative options for the management of anemia, such as the use of erythropoietin, aqueous oxygen, and hemoglobin-based oxygen carriers.

Topics: Anemia; Angioplasty, Balloon, Coronary; Blood Substitutes; Blood Transfusion; Coronary Disease; Erythropoietin; Fibrinolytic Agents; Fluorocarbons; Hematinics; Hemoglobins; Hemorrhage; Humans; Oxygen; Recombinant Proteins; Risk Factors

The relationship between haemoglobin (Hb) level and survival in patients with chronic kidney disease (CKD) is complex. This paper explores the physiological basis for the hypothesis that Hb level and survival are causally related in this patient group, and assesses the current state of knowledge from clinical studies. Issues related to the methodology and analysis of clinical studies limit the certainty with which conclusions regarding the direct relationship between Hb level and survival can be drawn. The data support the concepts that Hb level is associated with survival in patients both with and without CKD, that changes in Hb level are associated with cardiovascular disease (CVD), and that CVD is prevalent in patients with CKD. Hb level is affected by nutritional status, inflammation, and the availability and effectiveness of human recombinant erythropoietin (rHuEPO) therapy, as well as by the degree of kidney function. Thus, the complexity of the relationships between Hb level, CVD and survival in patients with CKD requires further study from both the mechanistic and the clinical perspective. Properly designed clinical trials with survival as an endpoint, as well as data from prospectively measured modifiers of Hb levels and other markers of CVD, are needed to determine the physiological and statistical interaction of these factors in clinical practice.

Topics: Apoptosis; Coronary Disease; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Survival Analysis

This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Blood Pressure; Coronary Disease; Drug Hypersensitivity; Erythropoietin; Humans; Injections, Intravenous; Iron; Iron Deficiencies; Iron, Dietary; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Recombinant epoetin therapy and correction of the chronic anemia of renal failure have greatly reduced the number of red cell transfusions and hence the propensity to iron overload. The majority of HD patients require intravenous iron therapy to achieve the hematocrit levels that correspond to improved outcome measures. Although the short-term benefits of intravenous iron have been clearly defined, the long-term risks of intravenous iron are less well-defined. Iron overload before the availability of epoetin constituted a serious problem; our review of the literature does not decisively conclude that these patients had more serious bacterial infections or increased mortality when compared with their non-iron overloaded counterparts, unless chronic transfusion-related hepatic disease was superimposed. Specifically, no data unequivocally confirm that iron overload from parenteral iron contributes to all-cause patient morbidity or mortality. Furthermore, therapy that maintains intravenous iron optimal iron stores and replaces iron losses associated with the dialytic procedure does not engender iron overload in the carefully monitored patient. Optimized anemia therapy in ESRD requires individualized and specific application of epoetin and iron for each patient, and significant cost savings can result from such a strategy. Prospective studies are clearly necessary to define those parameters that reflect adequacy of iron storage in renal failure patients. We should develop alternative means of iron delivery and develop monitors that accurately discriminate between patients who will respond to additional iron therapy and those who will not. Whether ferritin should be supplanted by another parameter and whether iron itself poses an increased risk to those patients it has so beneficially served are issues that must be resolved. Until these answers are known, the importance of carefully crafted iron therapy cannot be overstated.

Topics: Anemia; Coronary Disease; Erythropoietin; Female; Free Radicals; Humans; Infections; Injections, Intravenous; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Recombinant Proteins; Risk Factors; Safety; Transferrin

To investigate an appropriate hematocrit (Hct) for managing renal anemia complicated by angina pectoris at rest.. Nonrandomized, retrospective and prospective observational study.. Sapporo Medical University Hospital, Sapporo, Japan.. Thirty-two anemic patients (aged 62 +/- 10 years, range 40 to 78) with rest angina in end-stage renal failure.. Serial changes of exercise tolerance (estimated metabolic equivalents [METs] on stress electrocardiography produced by improvement of patients' Hct, using recombinant human erythropoietin (rHuEPO). Adverse effects, such as deteriorating systemic hypertension, were investigated with regard to the severity of coronary arteriographic findings (Leaman's score) and cardiac events within a six-month period.. Higher Hct was clearly correlated with better estimated METs: when Hct was less than 20%, MET was 1.4 +/- 0.5; with 20% < or = Hct < 25% 2.1 +/- 1.4; with 25% < or = Hct < 30% 3.1 +/- 1.6; and with 30% < or = Hct < 35% 4.9 +/- 1.1. Patients with cardiac events (elective balloon angioplasty [n = 5], bypass surgery [n = 1], myocardial infarction [n = 2] and hospital death from congestive heart failure [n = 3]) had advanced coronary lesions compared with patients without coronary events (Leaman's score 15.9 +/- 9.3 versus 7.3 +/- 4.4, respectively, P < 0.01) and lower exercise capacity at 25% < or = Ht < 30% (estimated METs 2.4 +/- 1.2 versus 3.9 +/- 1.9, respectively, P < 0.05). Moreover, there was an inverse linear correlation between estimated METs and Leaman's score only when Hct was over 25%. In prospectively examined subjects (n = 16), Hct 35% or greater without systemic hypertension was obtained in only seven (44%), and no additional effect on exercise tolerance was expected when Hct was 35% or greater.. Managing renal anemia with 30% < or = Hct < 35% with rHuEPO is considered an appropriate therapy in patients with end-stage renal failure complicated by rest angina.

Topics: Adult; Aged; Anemia; Coronary Disease; Erythropoietin; Female; Hematocrit; Humans; Informed Consent; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Retrospective Studies

Atherosclerosis is a progressive disease characterised in part by an imbalance of endothelial decline and endothelial repair. Erythropoietin has been connected to vasculoprotective effects such as enhanced nitric oxide production in endothelial cells and mobilisation of endothelial progenitor cells (EPC).. To determine the effect of erythropoietin on endothelial function and EPC mobilisation in humans with atherosclerosis.. A prospective single-blind monocentric study of 20 patients randomly assigned to the test drug or placebo treatment over 4 weeks.. 20 Patients with stable coronary artery disease receiving optimal medical treatment with either weekly subcutaneous injections of saline (placebo) or the recombinant erythropoietin darbepoetin (60 μg/injection) over 3 consecutive weeks. At the initial and final visits, flow mediated dilatation (FMD) was determined by ultrasound. The number of EPC was determined as the number of CD34/CD133 positive mononuclear cells in peripheral blood.. Treatment with darbepoetin resulted in a significantly improved FMD in each patient, whereas no difference was seen in placebo-treated patients. The FMD of darbepoetin-treated patients increased by 7.5±1.64%. Additionally, an increase in peripheral blood EPC of 50±24% was seen.. Darbepoetin given in addition to optimal medical treatment resulted in a significantly improved endothelial function in patients with coronary artery disease, indicating a promising new atheroprotective treatment option.

Topics: Aged; Coronary Disease; Endothelial Cells; Endothelium, Vascular; Erythropoietin; Female; Flow Cytometry; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Stem Cells

This study evaluates the real effectiveness of epoetin-alpha associated with ferrous sulphate, in reducing blood transfusion in patients undergoing elective open heart surgery not treated with autologous donation.. Sixty patients had been divided into 2 groups: group A (30 patients) treated with 525 mg ferrous sulphate three time a day per os for 3 weeks; group B (30 patients) treated with epoetin-alpha 10,000 UI twice a week and 525 mg ferrous sulphate 3 times a day. Grouping of patients has been randomized. In both groups hemoglobin, hematocrit, reticulocytes, iron values, ferritine, transferrine, and serological values, have been evaluated sequentially before treatment, before surgery, day of operation, 1st, 2nd, 3rd, 7th postoperative days and at discharge.. In group A 86% patients needed blood transfusion (26 out of 30); in group B only 3% of patients needed blood transfusion (1 patient). One year follow up didn't show side effects related to epoetin-alpha.. This study confirms the real effectiveness of epoetin-alpha in reducing the postoperative need for homologous blood transfusion. No side effects due to epoetin-alpha treatment have been proved. The conclusion is drawn that epoetin-alpha can be used as an alternative to blood transfusion or in association with predeposit and in the treatment of basal anemia.

Topics: Blood Loss, Surgical; Coronary Disease; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Ferrous Compounds; Heart Valve Diseases; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins

We studied the effect of erythropoietin on the morphofunctional status of bone marrow mesenchymal stem cells in patients with coronary heart disease. It was shown that the duration of cell exposure with erythropoietin had different effects on the expression levels of adhesion molecules, erythropoietin receptors, and co-expression of the erythropoietin receptor and common β-chain of cytokines, apoptosis/necrosis, and the cell cycle. In most cases, erythropoietin increased proliferation, migration, and NO production by "aged" mesenchymal stem cells (passage 8) and passage 4 mesenchymal stem cells grown during the previous 3 passages in the presence of 33.4 U/ml erythropoietin. Erythropoietin increased the expression of the autophagy marker LC3B in mesenchymal stem cells grown in the presence of erythropoietin in the culture medium. Thus, long-term culturing of mesenchymal stem cells in the presence of erythropoietin in the culture medium increased their resistance to adverse microenvironment factors - oxidative stress and hyperglycemia.

Topics: Antigens, CD; Autophagy; Bone Marrow Cells; Cell Count; Cell Cycle; Cell Movement; Cell Proliferation; Coronary Disease; Erythropoietin; Gene Expression Regulation; Humans; Mesenchymal Stem Cells; Microtubule-Associated Proteins; Oxidative Stress; Primary Cell Culture; Receptors, Erythropoietin; Signal Transduction

AIM--to develop pathogenetic methods for the correction of dysregulated erythropoesis in coronary heart disease (CHD). 20 patients with myocardial Q-infarction and 52 ones with chronic CHD. 26 patients of the CHD group suffered anemia. Ten volunteers without signs of cardiovascular pathology served as controls. Characteristics of peripheral blood and iron metabolism, serum levels of inflammation markers and erythropoietin (EPO) were measured. In most CHD patients elevated levels of TNF-alpha inhibited hepatic synthesis of EPO. Low hepcidin production was associated with increased EPO levels and low iron content in blood. Anemia developing in CHD patients may cause not only inflammation but also depletion of iron reserves. Correction of dysregulated erythropoesis in coronary heart in CHD must be performed with due regard for the above mechanisms on an individual basis.

Topics: Aged; Coronary Disease; Drug Therapy, Combination; Erythropoiesis; Erythropoietin; Female; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Myocardial Infarction; Severity of Illness Index; Treatment Outcome

The hormones erythropoietin (EPO) and thrombopoietin (TPO) are main regulators of erythro- and thrombopoiesis. Cell loss caused by operative procedures may alter serum levels of the hormones, resulting in well known phenomenons like reactice thrombocytosis.. Blood samples from 10 patients (mean age 63 ± 9 years) were obtained before and at day 1, 5 and 10 after coronary artery bypass grafting (CABG). EPO and TPO levels were determined by commercially available ELISA-Kits (R&D Systems, Germany). In addition, platelet count (PC) and hemoglobin concentration (Hb) were determined.. Prior to CABG, EPO (13.2 ± 8.2 mU/mL), TPO (189 ± 52 pg/mL), Hb (8.8 ± 1.1 mmol/L) and PC (254 ± 121/nL) were within a normal range. At day 1 after surgery, Hb and PC were significantly decreased to 6.6 ± 0.9 mmol/L and 138 ± 70/nL. In contrast, EPO and TPO were significantly elevated to 32 ± 18 mU/mL and 336 ± 96 pg/mL, respectively, in spite of hemodilution. In particular, TPO elevation was followed by a significant increase in PC (342 ± 144/nL) at day 10 after surgery compared to preoperative values.. Appropriate to the decrease in hemoglobin concentration and platelet count, clear alterations of serum erythropoietin and thrombopoietin levels could postoperatively be observed. EPO levels showed an inverse correlation to hemoglobin concentrations, whereas a disturbed thrombopoietin feedback mechanism resulted in the phenomenon of reactive thrombocytosis.

Topics: Aged; Anemia; Coronary Artery Bypass; Coronary Disease; Elective Surgical Procedures; Erythropoietin; Feedback, Physiological; Female; Hemoglobins; Humans; Male; Middle Aged; Platelet Count; Postoperative Period; Thrombopoietin

Topics: Animals; Cell- and Tissue-Based Therapy; Cholesterol, LDL; Coronary Disease; Endothelial Cells; Erythropoietin; Extremities; Fibroblast Growth Factor 2; Humans; Ischemia; Lipid Metabolism Disorders; Myocardial Infarction; Niacin; Probucol

The aim of this study was to investigate whether erythropoietin (EPO) has cardioprotective effects in a chronic myocardial ischaemia model regarding strain-rate imaging parameters during dobutamine stress echocardiography (DSE).. An ameroid constrictor was placed around the circumflex artery in 13 pigs to induce hibernating myocardium by a chronic vessel occlusion. The pigs were randomized 14 days later: seven pigs receiving 10,000 U EPO and six pigs receiving placebo injected into the ischaemic region using a NOGAtrade mark-guided transendocardial catheter. At weeks 2 and 6, animals were examined by DSE, electromechanical mapping, and coronary angiography. During incremental dobutamine infusion, regional radial function was monitored by measuring peak systolic strain-rates (SRsys), systolic strains (epsilonsys), and post-systolic strains (epsilonps). At week 6, the animals were pathohistologically investigated. Echocardiography revealed 2.2+/-0.8 hypokinetic segments in the EPO-treated animals in comparison with 3.3+/-0.9 akinetic segments per animal in the controls. The mean ejection fraction was reduced in the control group (55+/-3 vs. 66+/-4%, P=0.057). Strain-rate imaging revealed ischaemic myocardium in EPO-treated animals and non-viable myocardium in the controls (P=0.0001). Histological analysis of the ischaemic region revealed a reduction of myocardial fibrosis (8+/-1 vs. 27+/-5%) in the EPO-treated group. The transmural extension of fibrosis and the echocardiographic deformation data correlated in the posterior walls (EPO group): epsilonsys at rest r=0.83; peak SRsys during dobutamine stimulation r=0.92, P=0.01.. Endocardial EPO injection may induce cardioprotective effects in chronic ischaemic myocardium and helps to obtain the myocardial contractile reserve, objectified by ultrasonic strain-rate imaging.

Topics: Animals; Cardiotonic Agents; Constriction; Coronary Disease; Dopamine; Echocardiography; Erythropoietin; Injections, Intralesional; Myocardial Stunning; Random Allocation; Recombinant Proteins; Stress, Mechanical; Swine; Systole; Ventricular Remodeling

Adeno-associated viral vectors (AAV) are attractive tool for gene therapy for coronary artery disease. However, gene expression in myocardium mediated by AAV serotype 2 (AAV2) does not peak until 4-6 weeks after gene transfer. This delayed gene expression may reduce its therapeutic potential for acute cardiac infarction. To determine whether earlier gene expression and better therapeutic effect could be achieved using a different serotype, CMV promoter driving the EPO gene (AAV-EPO) was packaged into AAV serotypes 1-5 capsids and injected into mouse myocardium. EPO expression was studied by measuring the hematocrits and EPO mRNA. After we found that AAV1 mediates the highest gene expression after 4 days of gene transduction, AAV-LacZ (CMV promoter driving LacZ gene expression) and MLCVEGF (hypoxia-inducible and cardiac-specific VEGF expression) were packaged into AAV1 and 2 capsids. LacZ expression was detected in AAV1-LacZ but not in AAV2-LacZ-injected hearts 1 day after vector injection. Compared to AAV2-MLCVEGF that mediated no significant VEGF expression, AAV1-MLCVEGF mediated 13.7-fold induction of VEGF expression in ischemic hearts 4 days after gene transduction and resulted in more neovasculatures, better cardiac function and less myocardial fibrosis. Thus, AAV1 mediates earlier and higher transgene expression in myocardium and better therapeutic effects.

Topics: Animals; Cell Proliferation; Coronary Disease; Dependovirus; Echocardiography; Erythropoietin; Female; Gene Expression; Genetic Engineering; Genetic Therapy; Genetic Vectors; Hematocrit; Hypoxia-Inducible Factor 1, alpha Subunit; Lac Operon; Male; Mice; Mice, Inbred Strains; Myocardium; Neovascularization, Physiologic; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Serotyping; Time; Transduction, Genetic; Vascular Endothelial Growth Factor A

An obese 76-year-old woman with type II diabetes, hypertension, coronary artery disease, and gastroesophageal reflux was found to have a 6-cm lower-pole mass in a solitary functional right kidney. Because her religious beliefs prohibited blood transfusion, minimally invasive surgery--a laparoscopic partial nephrectomy--was performed, with a good result. Minimally invasive surgery, perhaps with administration of erythropoietin, iron-dextran, or both, is often a good option for severely anemic patients or those whose religious beliefs are opposed to transfusion. Methods of minimizing blood loss intraoperatively are reviewed.

Topics: Aged; Carcinoma, Renal Cell; Coronary Disease; Diabetes Mellitus, Type 2; Erythropoietin; Female; Gastroesophageal Reflux; Humans; Hypertension; Iron-Dextran Complex; Jehovah's Witnesses; Kidney Neoplasms; Laparoscopy; Nephrectomy

Increasing evidence suggests that postnatal neovascularization involves the recruitment of circulating endothelial progenitor cells (EPCs). Hematopoietic and endothelial cell lineages share common progenitors. Cytokines formerly thought to be specific for the hematopoietic system have only recently been shown to affect several functions in endothelial cells. Accordingly, we investigated the stimulatory potential of erythropoietin (Epo) on EPC mobilization and neovascularization. The bone marrow of Epo-treated mice showed a significant increase in number and proliferation of stem and progenitor cells as well as in colony-forming units. The number of isolated EPCs and CD34+/flk-1+ precursor cells was significantly increased in spleen and peripheral blood of Epo-treated mice compared with phosphate-buffered saline-treated mice. In in vivo models of postnatal neovascularization, Epo significantly increased inflammation- and ischemia-induced neovascularization. The physiologic relevance of these findings was investigated in patients with coronary heart disease. In a multivariate regression model, serum levels of Epo and vascular endothelial growth factor were significantly associated with the number of stem and progenitor cells in the bone marrow as well as with the number and function of circulating EPCs. In conclusion, the present study suggests that Epo stimulates postnatal neovascularization at least in part by enhancing EPC mobilization from the bone marrow. Epo appears to physiologically regulate EPC mobilization in patients with ischemic heart disease. Thus, Epo serum levels may help in identifying patients with impaired EPC recruitment capacity.

Topics: Animals; Antigens, CD34; Bone Marrow Cells; Cell Count; Cell Division; Cell Movement; Coronary Disease; Endothelial Growth Factors; Endothelium, Vascular; Erythropoietin; Hindlimb; Humans; Intercellular Signaling Peptides and Proteins; Ischemia; Lymphokines; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Recombinant Proteins; Stem Cells; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors

Topics: Aged; Anemia, Pernicious; Blood Transfusion, Autologous; Coronary Artery Bypass; Coronary Disease; Erythropoietin; Humans; Male

An increase in blood pressure is common during treatment of renal anaemia with recombinant human erythropoietin (rhEPO). Concomitant findings of a decrease in cardiac output indicate that an increase in the peripheral flow resistance underlies the increase in blood pressure. The aim of this study was to elucidate the haemodynamic changes during rhEPO treatment in patients with ischaemic heart disease (IHD). Haemodynamic variables were assessed by impedance cardiography in 18 consecutive patients with renal anaemia before and after rhEPO treatment. IHD was found in eleven of these patients. The remaining seven served as controls. Before rhEPO treatment, the cardiac index was decreased in the group of patients with IHD, compared with controls and healthy subjects. Due to an increase in stroke index, the cardiac index increased during rhEPO treatment and reached values equal to those in the control group. The blood pressure increased and the increase in mean arterial pressure was correlated to the increase in cardiac index. Apparently the patients with IHD were unable to compensate for anaemia by increasing their cardiac index. Anaemia treatment increased cardiac index, which in turn caused an increase in blood pressure in these patients.

Topics: Adult; Aged; Anemia; Cardiac Output; Coronary Circulation; Coronary Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Hematocrit; Hemodynamics; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Recombinant Proteins; Renal Dialysis

We investigated the effects of recombinant human erythropoietin (rHuEPO) therapy on exercise capacity by symptom-limited maximal treadmill exercise testing in 9 patients with coronary artery disease who were receiving maintenance hemodialysis. The initial hemoglobin concentration of 7.9 +/- 0.7 g/dl, (mean +/- S.D.) rose to 10.4 +/- 1.1 g/dl, (p < 0.01) after three months of rHuEPO therapy. The partial correction of renal anemia resulted in a significant increase in exercise duration (from 278 +/- 84 sec to 384 +/- 74 sec, p < 0.01) and maximum pressure-rate product (from 228.3 +/- 50.3 mmHg.bpm/10(2) to 262.8 +/- 40.4 mmHg.bpm/10(2), p < 0.01). The maximum exercise-induced ST segment depression significantly decreased after treatment (from 1.3 +/- 0.5 mm to 0.5 +/- 0.5 mm, p < 0.05). These results suggest that the improvement in maximum coronary oxygen supply exceeded the increased maximum myocardial oxygen requirements after the partial correction of renal anemia by rHuEPO therapy in hemodialysis patients with coronary artery disease.

Topics: Adult; Anemia; Coronary Disease; Erythropoietin; Exercise Test; Female; Humans; Male; Middle Aged; Physical Endurance; Recombinant Proteins; Renal Dialysis

From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.

Topics: Adult; Anemia; Coronary Disease; Erythropoietin; Exercise; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Renal Dialysis

A 78-year-old woman was diagnosed as having three-vessel coronary artery disease. A coronary artery bypass operation with autologous blood transfusion was indicated because of the irregular antibody and because homologous blood transfusion would lead to hemolytic complications. Since she had anemia (hemoglobin level, 10.7 g/dl) and autologous blood could not be collected, recombinant human erythropoietin (rHuEPO) and iron preparations were administered intravenously every day. The hemoglobin level reached 12.1 g/dl two weeks after administration, and then autologous blood was donated. The first 1200 ml of blood was stored frozen, and the last 400 ml as liquid in consideration of the blood preservation period. Surgery was performed uneventfully after 8 weeks of rHuEPO administration. No homologous blood transfusion was required during and after surgery. By using rHuEPO, it is thus possible to perform heart surgery without homologous blood transfusion even in patients with anemia, for whom blood transfusions have been considered necessary.

Topics: Aged; Anemia; Antibodies; Blood Transfusion, Autologous; Coronary Artery Bypass; Coronary Disease; Erythropoietin; Female; Humans; Recombinant Proteins

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

Topics: Coronary Disease; Epoetin Alfa; Erythropoietin; Heart Failure; Hematocrit; Humans; Immunization, Passive; Leukocyte Count; Pulmonary Heart Disease; Reticulocytes; Rheumatic Heart Disease; Serum