losartan-potassium and Heart-Valve-Diseases

We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to the high hematocrit (HCT) achieved in the animals. However, similarly high HCT was achieved in both high-dose and low-dose groups, but there were no reported adverse events in the low-dose group suggesting HCT was not the sole contributing factor leading to toxicity. Our analysis indicated that increased dose, dose frequency, and dosing duration in addition to high HCT contributed to mortality and thrombosis. To further evaluate this relationship, the incidence of toxicities was compared in rats administered an experimental hyperglycosylated analog of recombinant human erythropoietin (AMG 114) at varying dosing schedules in 1-month toxicity studies. The incidence of mortality and thrombotic events increased in higher dose groups and when dosed more frequently, despite a similarly high HCT in all animals. The results from the investigative study and retrospective analysis demonstrate that ESA-related toxicities in preclinical species are associated with dose level, dose frequency, and dosing duration, and not solely dependent upon a high HCT.

Topics: Animals; Biomedical Research; Dogs; Erythropoiesis; Erythropoietin; Heart Valve Diseases; Hematinics; Hematocrit; Humans; Macaca fascicularis; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Retrospective Studies; Stomach Neoplasms; Thrombosis

Blood-sparing surgical technique and perioperative medical management allows complex surgery in Jehovah's Witnesses. The authors review four cases of urgent cardiothoracic surgery performed on Jehovah's Witnesses. No lasting sequelae associated with either bleeding or end-organ ischemia were noted. Cardiopulmonary bypass management, meticulous hemostatic operative technique, and pharmacologic support of hemostasis and erythropoiesis permit this complex surgery.

Topics: Adult; Aged; Anti-Bacterial Agents; Aortic Aneurysm; Aortic Dissection; Aprotinin; Blood Transfusion, Autologous; Blood Vessel Prosthesis Implantation; Cardiac Surgical Procedures; Cardiac Tamponade; Combined Modality Therapy; Comorbidity; Endocarditis, Bacterial; Erythropoietin; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hematocrit; Hemodilution; Humans; Iron; Jehovah's Witnesses; Male; Patient Acceptance of Health Care; Preoperative Care; Streptococcal Infections; Treatment Refusal; Viridans Streptococci

Topics: Adult; Aged; Anemia; Blood Transfusion; Bone Marrow Transplantation; Cardiac Surgical Procedures; Endocarditis, Bacterial; Erythropoietin; Extracorporeal Circulation; Heart Valve Diseases; Humans; Middle Aged; Postoperative Complications

Recombinant human erythropoietin (EPO) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties. The aim of this single-site, randomized, case-controlled, and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury (AKI) in patients with risk factors for AKI undergoing complex valvular heart surgery.. We studied ninety-eight patients with preoperative risk factors for AKI. The patients were randomly allocated to either the EPO group (n = 49) or the control group (n = 49). The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction. The control group received an equivalent volume of normal saline. AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Biomarkers of renal injury were serially measured until five days postoperatively.. Patient characteristics and operative data, including the duration of cardiopulmonary bypass, were similar between the two groups. Incidence of postoperative AKI (32.7% versus 34.7%, P = 0.831) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups. The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups. None of the patients developed adverse complications related to EPO administration, including thromboembolic events, throughout the study period.. Intravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery.. Clinical Trial.gov, NCT01758861.

Topics: Acute Kidney Injury; Biomarkers; Cardiopulmonary Bypass; Case-Control Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Heart Valve Diseases; Hematinics; Hematocrit; Humans; Incidence; Kidney Function Tests; Male; Middle Aged; Postoperative Complications; Recombinant Proteins; Risk Factors; Treatment Outcome

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

Based on its pleiotropic effects, erythropoietin can decrease inflammation, oxidative stress, and apoptosis. Erythropoietin provides organ protection for the heart, brain, and kidney in diverse preclinical animal studies, especially models that include ischemia-reperfusion injury and/or inflammation. However, large clinical studies in coronary reperfusion, heart failure, stroke, acute kidney injury, and chronic renal disease have failed to demonstrate improved outcomes. A study in a previous issue of Critical Care examining the ability of erythropoietin to prevent or ameliorate acute kidney injury in patients undergoing complex valvular heart surgery is similarly negative. The failure of erythropoietin in clinical studies may be due to an inadequate dose, since the receptors responsible for organ protection may require higher concentrations than those responsible for erythropoiesis. However, as has occurred in studies in sepsis and acute respiratory distress syndrome, the negative studies probably reflect an inadequate understanding of the complexity of the underlying processes with multiple redundant and interacting pathways that may differ among the large number of different cell types involved. As tools to understand this complexity and integrate it on an organismal basis continue to evolve, we will develop the ability to use erythropoietin and related nonhematopoietic agents for organ protection.

Topics: Acute Kidney Injury; Erythropoietin; Female; Heart Valve Diseases; Hematinics; Humans; Male; Postoperative Complications

Preoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.

Topics: Aged; Anemia; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hematinics; Hospital Mortality; Humans; Infusions, Intravenous; Male; Postoperative Period; Preoperative Care; Prospective Studies; Recombinant Proteins; Risk Factors; Spain; Sucrose; Survival Rate; Treatment Outcome

The hemorheological effects of autologous blood storage with or without the use of erythropoietin were examined before surgery for valvular disease. There was no rheological difference between patients with aortic (16 cases) or mitral (10 cases) valve disease. Before storage, the levels of hematocrit, whole blood viscosity, and especially coefficient of rheology, were lower (p < 0.05) in the blood stored with erythropoietin, but this difference disappeared after storage. The plasma viscosity of both groups did not change before and after storage. The viscosity of blood was equalized after the storage of blood, irrespective of the use of erythropoietin.

Topics: Adult; Aged; Blood Preservation; Blood Transfusion, Autologous; Blood Viscosity; Erythropoietin; Female; Heart Valve Diseases; Hematocrit; Humans; Male; Middle Aged

Open-heart surgery has been performed since 1975 on 25 patients who are Jehovah's Witnesses by religion. The patients' ages ranged from 6-60 years, and their body weights from 18-51 kg. Surgical procedures included correction of congenital heart disease in 14 patients and valve repair or replacement in 11. Six procedures were reoperations. The lowest mean haematocrits, during perfusion and the postoperative period, were 22.7% (range 15.0-31.0%) and 27% (range 16.0-36.0%), respectively. Twenty-four patients survived and are alive and well. One patient died of low output failure before discharge. The blood return system reduced blood loss. Five of the patients who underwent cardiac surgery received recombinant erythropoietin before and after surgery, leading to higher postoperative haematocrits. In one patient, a haematocrit which fell to 16.9% after surgery was raised to 27% by administration of erythropoietin, without blood transfusion. In two recent cases, high doses of aprotinin were used during surgery, resulting in better haemostasis after cardiopulmonary bypass.

Topics: Adolescent; Adult; Blood Loss, Surgical; Child; Christianity; Erythropoietin; Female; Heart Defects, Congenital; Heart Valve Diseases; Hematocrit; Humans; Male; Middle Aged; Platelet Count; Postoperative Hemorrhage; Recombinant Proteins; Religion and Medicine; Reoperation; Survival Rate

Topics: Aged; Anemia, Refractory; Erythropoietin; Heart Valve Diseases; Hemolysis; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

This study was performed to determine the effect of recombinant human erythropoietin (rEPO) on preoperative autologous blood donation in patients undergoing elective coronary bypass or valvular operations. Nineteen patients received 200 u/kg of rEPO intravenously 3 times a week, and 210 mg/day of iron sulfate orally, for 2 weeks before surgery (EPO group). Seven matched patients only took the same dose of iron sulfate (control group). Bone marrow was aspirated from the sternum during surgery, and the Myeloids/Erythroids ratio was calculated in 13 patients of the EPO group. The total donated blood mass was 853 +/- 231 g in the EPO group, and 657 +/- 140 g in the control group (p < 0.05). The average increase in hemoglobin (Hb) mass from admission to the day before surgery was 87 +/- 33 g in the EPO group, and 24 +/- 13 g in the control group (p < 0.001). Furthermore, the logarithm of the ratio of "increased Hb mass/Hb mass at admission" was significantly correlated to the Myeloids/Erythroids ratio (r = -0.9130, p < 0.01). These results strongly indicate that rEPO is a very useful agent for predonation of autologous blood for cardiac operations.

Topics: Adult; Bone Marrow; Cardiac Surgical Procedures; Cell Count; Coronary Artery Bypass; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Heart Valve Diseases; Hemoglobins; Humans; Iron; Male; Middle Aged; Premedication; Recombinant Proteins