losartan-potassium and Cardiomyopathies

Sudden cardiac arrest is a leading cause of death worldwide with survival rates still remaining suboptimal. Unfortunately, most cardiac arrest patients, who achieve return of spontaneous circulation (ROSC), develop a multi-faceted post-cardiac arrest syndrome, including post-cardiac arrest brain injury, myocardial dysfunction, and systemic ischemia/reperfusion response. Erythropoietin (EPO), the principal hematopoietic hormone regulating erythropoiesis, exhibits diverse cellular effects in nonhematopoietic tissues. Due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, as well as its angiogenic action, EPO plays a role in neuroprotection and cardioprotection. In this regard, EPO represents a promising agent in the cardiac arrest setting, based on a therapeutic strategy that focuses on the post-resuscitation phase. This review aims to provide a comprehensive account of EPO's role in the treatment of each individual component of post-cardiac arrest syndrome.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Diseases; Cardiomyopathies; Cardiotonic Agents; Erythropoietin; Heart Arrest; Humans; Reperfusion Injury; Syndrome

The use of erythropoietin (EPO) has revolutionized the treatment of anaemia associated with many conditions including chronic kidney disease (CKD). However, little is known of the cellular impact of EPO on the uraemic heart. The discovery that the EPO receptor (EPOR) is also expressed on non-haematopoietic cells including cardiomyocytes highlights a role of EPO beyond haematopoiesis. Animal models of heart failure have shown EPO can potentially reverse cardiac remodelling and improve myocardial function. Damage to the kidney, during uraemia, results in a decreased EPO production, which may render the uraemic heart more susceptible to damage and heart failure. Here we review current data on the cellular actions of EPO in models of left ventricular hypertrophy and heart failure and highlight parallels with the uraemic heart.

Topics: Cardiomyopathies; Erythropoietin; Fibrosis; Humans; Hypertrophy, Left Ventricular; Myocardium; Receptors, Erythropoietin; Risk Factors; Signal Transduction; Uremia; Ventricular Remodeling

Carnitine is a metabolic cofactor which is essential for normal fatty acid metabolism. Patients with chronic kidney disease on dialysis have been shown both to suffer from disordered fatty acid metabolism and to have a significant deficiency in plasma and tissue carnitine. Aberrant fatty acid metabolism has been associated with a number of cellular abnormalities such as increased mitochondrial permeability (a promoter of apoptosis), insulin resistance, and enhanced generation of free radicals. These cellular abnormalities have, in turn, been correlated with pathological clinical conditions common in dialysis patients including cardiomyopathy with attendant hypotension and resistance to the therapeutic effect of recombinant human erythropoietin (EPO). In 1999, the Food and Drug Administration approved levocarnitine injection for the prevention and treatment of carnitine deficiency in patients on dialysis based on documentation of free plasma carnitine levels in dialysis patients similar to other serious carnitine deficiency states for which treatment was required. Data analysis performed by expert panels convened by both the American Association of Kidney Patients and, subsequently, the National Kidney Foundation recommended a trial of levocarnitine therapy for specific subsets of dialysis patients including those with EPO resistance, dialysis-related hypotension, cardiomyopathy and muscle weakness. In 2003, the Centers for Medicare and Medicaid services convened a Medical Advisory Committee which established reimbursement on a national level for carnitine-deficient dialysis patients who had either dialysis-related hypotension or EPO resistance. Recently, a correlation between reductions in hospitalization rates of dialysis patients receiving levocarnitine therapy has been demonstrated in a large retrospective study. Despite data-based recommendations and national reimbursement, only a small minority of dialysis patients have been prescribed a therapeutic trial of levocarnitine. Whereas the reasons for the reluctance of nephrologists to prescribe this therapeutic trial are unclear, possible explanations include a lack of appreciation of the pivotal role played by carnitine in cellular metabolism and the strength of evidence for a substantial deficiency of carnitine in dialysis patients, an underestimation of the prognostic import of EPO resistance and dialysis-related hypotension, inadequate dissemination of the clinical trial data supporting the use of le

Topics: Acetylcarnitine; Anemia; Cardiomyopathies; Drug Resistance; Erythropoietin; Humans; Hypotension; Recombinant Proteins; Renal Dialysis; Vitamin B Complex

The combination of heart failure and chronic kidney disease (CKD) has received comparatively little attention in terms of clinical research versus investigations of each state individually. It has been known for over a decade that anemia, a cardinal feature of CKD, is associated with higher cardiovascular event rates in late-stage and end-stage renal disease. Although the biological mechanisms linking anemia, renal failure, and heart failure are incompletely understood, more prevalent anemia is consistent in patients with more severe heart failure and is associated with higher mortality rates. Impaired erythropoietin production and resistance to erythropoietin are major contributors to anemia in patients with heart failure. By targeting hemoglobin levels in anemic patients with CKD, through the use of recombinant erythropoietin (epoetin) therapy, it has been hoped that anemia, CKD, and heart failure outcomes can be improved. Darbepoetin alfa was engineered to contain more N-linked carbohydrate chains than erythropoietin, and has an approximately 3 times longer serum half-life. Several clinical trials have addressed the hypothesis that darbepoetin alfa can effectively treat renal anemia at dose frequencies of once per week, or less often, with positive outcomes.

Topics: Anemia; Cardiomyopathies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

The target hematocrit to be achieved when treating anemia in hemodialysis patients with erythropoietin is controversial. Current evidence-based recommendations suggest a target hematocrit range of 33% to 36%. Small studies suggest that normalization of hematocrit with erythropoietin may benefit hemodialysis patients in terms of brain function, physical performance, quality of life, and prevention of progressive left ventricular dilatation. However a recent study of the effects of erythropoietin-induced normalization of hematocrit in hemodialysis patients with symptomatic heart disease has shown an increase in both mortality and the rate of vascular access thrombosis. Currently, normalization of hematocrit in patients with symptomatic heart disease is not recommended, nor is it possible to conclude that possible benefits of normalization of hematocrit will outweigh risks in hemodialysis patients without symptomatic heart disease.

Topics: Anemia; Cardiomyopathies; Cardiovascular Diseases; Clinical Trials as Topic; Cognition; Erythropoietin; Exercise; Hematocrit; Humans; Iron; Recombinant Proteins; Renal Dialysis; Uremia

Increased oxidative and nitrosative stress are important mediators of left ventricular (LV) and vascular dysfunction in patients with chronic heart failure (CHF). This study investigated the effects of darbepoetin alfa on plasma markers of oxidative and nitrosative stress in patients with CHF with anemia. Thirty patients with CHF (LV ejection fraction [LVEF] <40%, hemoglobin <12.5 g/dl, and serum creatinine <2.5 mg/dl) were randomly assigned (1:1) to receive either a 3-month darbepoetin alfa regimen at 1.5 microg/kg every 20 days plus oral iron or placebo plus oral iron. Plasma B-type natriuretic peptide (BNP), markers of oxidative (oxidative, malondialdehyde, carbonyl proteins; antioxidative, glutathione) and nitrosative (nitrotyrosine) stress, LVEF, and 6-minute walked distance were assessed at baseline and after treatment. A significant improvement in LVEF and 6-minute walked distance was observed in only darbepoetin-treated patients. Plasma BNP (F = 14.8, p = 001), malondialdehyde (F = 9.4, p = 0.006), protein carbonyl (F = 9.2, p = 0.006), and nitrotyrosine (F = 4.4, p = 0.045) were significantly decreased, along with an increase in antioxidative glutathione (F = 4.2, p = 0.049) after darbepoetin alfa treatment. These factors were unaffected in placebo-treated patients. Darbepoetin-induced percentages of change in carbonyl protein significantly correlated with respective changes in plasma BNP (r = 0.55, p <0.05) and LVEF (r = -0.46, p <0.05). Finally, a drug-induced percentage of decrease in nitrotyrosine significantly correlated with the respective improvement in 6-minute walked distance (r = -0.63, p <0.05). In conclusion, darbepoetin alfa attenuated deleterious effects of oxidative and nitrosative stress into the cardiovascular system of anemic patients with CHF, improving also cardiac function and exercise capacity.

Topics: Aged; Anemia; Cardiomyopathies; Chronic Disease; Darbepoetin alfa; Erythropoietin; Exercise Tolerance; Female; Heart Failure; Hematinics; Humans; Male; Middle Aged; Nitrosation; Oxidative Stress

Activation of renin-angiotensin system (RAS) is one of the pathological mechanisms associated with myocardial ischemia-reperfusion injury following resuscitation. The present study aimed to determine whether erythropoietin (EPO) improves post‑resuscitation myocardial dysfunction and how it affects the renin‑angiotensin system. Sprague‑Dawley rats were randomly divided into sham, vehicle, epinephrine (EP), EPO and EP + EPO groups. Excluding the sham group, all groups underwent cardiopulmonary resuscitation (CPR) 4 min after asphyxia‑induced cardiac arrest (CA). EP and/or EPO was administrated by intravenous injection when CPR began. The results demonstrated that the vehicle group exhibited lower mean arterial pressure, left ventricular systolic pressure, maximal ascending rate of left ventricular pressure during left ventricular isovolumic contraction and maximal descending rate of left ventricular pressure during left ventricular isovolumic relaxation (+LVdP/dt max and ‑LVdP/dt max, respectively), and higher left ventricular end‑diastolic pressure, compared with the sham group following return of spontaneous circulation (ROSC). Few significant differences were observed concerning the myocardial function between the vehicle and EP groups; however, compared with the vehicle group, EPO reversed myocardial function indices following ROSC, excluding‑LVdP/dt max. Serum renin and angiotensin (Ang) II levels were measured by ELISA. The serum levels of renin and Ang II were significantly increased in the vehicle group compared with the sham group, which was also observed for the myocardial expression of renin and Ang II receptor type 1 (AT1R), as determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. EPO alone did not significantly reduce the high serum levels of renin and Ang II post-resuscitation, but changed the protein levels of renin and AT1R expression in myocardial tissues. However, EPO enhanced the myocardial expression of Ang II receptor type 2 (AT2R) following ROSC. In conclusion, the present study confirmed that CA resuscitation activated the renin‑Ang II‑AT1R signaling pathway, which may contribute to myocardial dysfunction in rats. The present study confirmed that EPO treatment is beneficial for protecting cardiac function post‑resuscitation, and the roles of EPO in alleviating post‑resuscitation myocardial dysfunction may potentially be associated with enhanced myocardial expression of AT2R.

Topics: Angiotensin II; Animals; Biomarkers; Cardiomyopathies; Cardiopulmonary Resuscitation; Erythropoietin; Female; Gene Expression Regulation; Heart Arrest; Male; Myocardium; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin

The aim of this study was to investigate the protective effect of erythropoietin (EPO) against acute myocardial injury and its underlying mechanisms. Mice (n=146) were randomly divided in a double‑blind manner into four groups, sham, Rocephin, EPO and sepsis, and mortality was observed on the seventh day after cecal ligation and puncture. In addition, a total of 252 rats were randomly divided into three groups, sham, EPO and sepsis, and indicators of cardiac function, inflammatory mediators and serum creatine kinase levels were assessed. Mitochondrial membrane potential, cell apoptosis and nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) p65 expression levels were detected using flow cytometry. Following intervention with EPO, the mortality rate in mice with sepsis was significantly reduced and the cardiac function of septic rats was significantly improved. In addition, the levels of inflammatory mediators, serum creatine kinase and apoptosis and the myocardial mitochondrial membrane potential and expression of NF‑κB p65 in cardiac tissue were all improved following EPO treatment, and the differences between the results for the sepsis and EPO groups were statistically significant (P<0.05). These findings suggest that EPO reduces the myocardial inflammatory response in septic rats, attenuates the reduction in mitochondrial membrane potential and inhibits myocardial cell apoptosis by reducing NF‑κB p65 expression, and therefore exerts a protective effect in the myocardium.

Topics: Animals; Apoptosis; Biomarkers; Cardiomyopathies; Cardiotonic Agents; Cytokines; Disease Models, Animal; Erythropoietin; Hemodynamics; Inflammation Mediators; Male; Membrane Potential, Mitochondrial; Mice; Mortality; Rats; Sepsis; Time Factors; Transcription Factor RelA

Erythropoietin exerts cardioprotective effects. The present study aimed to investigate the therapeutic effects of erythropoietin on cirrhotic cardiomyopathy.. Rats were divided into 5 groups: sham control; sham+ erythropoietin; bile duct ligation; bile duct ligation+erythropoietin; bile duct ligation+erythropoietin+anti-tumour necrosis factor alpha (TNFα) antibody and were studied 4 wk after surgery. Erythropoietin was administrated for 10 days before the study date. TNFα, erythropoietin receptor-1 expression and oxidative stress-related parameters were measured. In separate groups, isolated cardiomyocytes were subjected to contractile and relaxation studies. Cardiomyocyte cell line was used to test the direct effect of erythropoietin on nuclear factor (erythroid-derived 2)-like 2(Nrf2).. Erythropoietin receptor-1, TNFα and oxidative modified proteins were significantly increased (p<0.01), and the antioxidant regulator Nrf2 transcription decreased in cirrhotic hearts (p<0.01). Erythropoietin reversed these parameters. Maximal cardiac contractile and relaxation velocity was significantly decreased in cirrhotic cardiomyocytes. Erythropoietin significantly reversed these inhibitions. Anti-TNFα antibody significantly decreased cardiac TNFα content but did not further increase contractility.. TNFα and oxidative stress are involved in cardiac dysfunction in the cirrhotic heart. Erythropoietin significantly decreased TNFα and oxidative stress and reversed the impaired cardiac function.

Topics: Animals; Biomarkers; Blotting, Western; Cardiomyopathies; Cardiovascular Agents; Erythropoietin; Heart; Liver Cirrhosis, Experimental; Male; Myocardium; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome; Tumor Necrosis Factor-alpha

Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P < 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Cardiomyopathies; Darbepoetin alfa; Drug Resistance; Erythropoietin; Gene Expression Regulation; Hematinics; Lipopolysaccharides; Male; Myocardium; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Inbred Lew; Sepsis; Tumor Necrosis Factor-alpha; Ventricular Function, Left

Doxorubicin (DOX) is an effective antineoplastic agent whose use has been limited by its cardiotoxic side effects. Recent studies have established that erythropoietin (EPO), a cytokine essential for red blood cell production, protects against ischemic injury in the heart and other organs. The purpose of this study was to assess whether EPO protects the heart against cardiotoxicity induced by DOX. We found that DOX-induced apoptosis and impaired heart function in mice were largely prevented by EPO administration. To investigate the mechanism of protection by EPO, cultured neonatal mouse ventricular myocytes were treated with EPO at therapeutic levels (i.e., 1 U/ml), before application of DOX (0.1-1.0 microM). EPO protected against DOX-induced cardiomyocyte death (by approximately 50%) and apoptosis assessed by annexin-V labeling, DNA fragmentation, and caspase-3 activity. DOX-mediated increases in reactive oxygen species, which trigger cardiotoxicity, were also reversed by preconditioning with EPO. These functional effects of EPO correlated with increased Akt/protein kinase B ( approximately 2-fold) and glycogen synthase kinase 3 (GSK-3; approximately 1.3-fold) phosphorylations, suggesting protection by EPO was mediated by phosphatidylinositol 3-kinase activation. Indeed, preventing Akt and GSK-3beta phosphorylations by phosphatidylinositol 3-kinase (PI3K) inhibition abolished protection by EPO against cardiomyocyte loss, apoptosis, and oxidative stress. Thus, pretreatment with therapeutic levels of EPO can protect the myocardium against DOX-induced impaired heart function and cardiomyocyte apoptosis by activating PI3K-Akt cell survival pathways.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Cardiomyopathies; Cardiotonic Agents; Cell Survival; Cells, Cultured; Doxorubicin; Erythropoietin; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart; Heart Rate; Male; Mice; Mice, Inbred Strains; Myocardium; Myocytes, Cardiac; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Receptors, Erythropoietin

Doxorubicin (DOX) is a highly effective chemotherapeutic agent related to dose-dependent cardiomyopathy. Recent evidence suggests that erythropoietin (EPO) can play a protective role in cardiovascular diseases by non-erythropoietic effects. In the present study, we tested the hypothesis that EPO may protect against DOX-induced cardiomyopathy through anti-apoptotic mechanisms both in vitro and in vivo.. Isolated neonatal Wistar rat cardiomyocytes were treated with vehicle, DOX with or without EPO, or EPO. Twenty-four hours later, the cells were used to determine cardiomyocyte apoptosis (TUNEL assay). Cardiomyopathy was induced in Wistar rats by intraperitoneal injections (IP) of DOX (2.5 mg/kg, six times for 2 weeks). EPO (2,500 U/kg, six times for 2 weeks) was administered simultaneously in the DOX+EPO group and the EPO group. Two weeks after the last administration, cardiac function was evaluated by echocardiography and invasive haemodynamic measurements. Rats were then sacrificed for histological and TUNEL analyses, with immunological detection for cardiac Troponin-T (cTnT), alpha-actinin, Bax and Bcl-2.. EPO significantly ameliorated DOX-induced apoptosis of cultured cardiomyocytes as demonstrated by TUNEL assay. In the rat model, cardiac function significantly decreased in the DOX group. In contrast, the DOX+EPO group showed considerable improvement in cardiac function, inhibition of cardiomyocyte apoptosis, reduction of fibrosis, as well as up-regulation of Bcl-2 protein expression.. Our results suggest that EPO exerts preventive cardioprotective effects on DOX-induced cardiomyopathy via anti-apoptotic pathways. The up-regulation of Bcl-2 protein expression may contribute to this.

Topics: Actinin; Animals; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cardiomyopathies; Cardiotonic Agents; Disease Models, Animal; Doxorubicin; Echocardiography; Erythropoietin; Immunohistochemistry; In Situ Nick-End Labeling; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Troponin T

Doxorubicin is a highly effective antineoplastic drug, but its clinical use is limited by its adverse side effects on the heart. We investigated possible protective effects of erythropoietin against doxorubicin-induced cardiomyopathy.. Cardiomyopathy was induced in mice by a single intraperitoneal injection of doxorubicin (15 mg/kg). In some cases, human recombinant erythropoietin (5000 U/kg) was started simultaneously. Two weeks later, left ventricular dilatation and dysfunction were apparent in mice given doxorubicin but were significantly attenuated by erythropoietin treatment. Erythropoietin also protected hearts against doxorubicin-induced cardiomyocyte atrophy and degeneration, myocardial fibrosis, inflammatory cell infiltration, and downregulation of expression of GATA-4 and 3 sarcomeric proteins, myosin heavy chain, troponin I, and desmin. Cyclooxygenase-2 expression was upregulated in doxorubicin-treated hearts, and that, too, was attenuated by erythropoietin. No doxorubicin-induced apoptotic effects were seen, nor were any changes seen in the expression of tumor necrosis factor-alpha or transforming growth factor-beta1. Antiatrophic and GATA-4 restoring effects of erythropoietin were demonstrated in the in vitro experiments with cultured cardiomyocytes exposed to doxorubicin, which indicated the direct cardioprotective effects of erythropoietin beyond erythropoiesis. Cardiac erythropoietin receptor expression was downregulated in doxorubicin-induced cardiomyopathy but was restored by erythropoietin. Among the downstream mediators of erythropoietin receptor signaling, activation of extracellular signal-regulated kinase was reduced by doxorubicin but restored by erythropoietin. By contrast, erythropoietin was ineffective when administered after cardiac dysfunction was established in the chronic stage.. The present study indicates a protective effect of erythropoietin against doxorubicin-induced cardiomyopathy.

Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Caspase 3; Caspases; Cells, Cultured; Cyclooxygenase 2; Cytokines; Doxorubicin; Erythrocyte Count; Erythropoietin; GATA4 Transcription Factor; Heart Failure; In Situ Nick-End Labeling; Mice; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Receptors, Erythropoietin; Sarcomeres; Survival Rate; Ventricular Dysfunction, Left

Topics: Adolescent; Anemia; Anti-Inflammatory Agents; Cardiomyopathies; Epoetin Alfa; Erythropoietin; Fluorescein Angiography; Humans; Injections; Laser Coagulation; Male; Methylprednisolone; Methylprednisolone Acetate; Muscular Dystrophy, Duchenne; Recombinant Proteins; Retinal Neovascularization; Vision Disorders; Vitrectomy; Vitreous Hemorrhage

Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Dox-induced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction.. Wistar rats were either treated with two different doses of Epo (20U or 200U) or PBS (n = 40 in each group) for four consecutive weeks, followed by Dox administration. In a second study, EPC obtained from healthy rats were transfused intravenously (n = 20/group) prior to induction of Dox cardiomyopathy. EPC from healthy subjects were evaluated for their proliferative and migratory properties in the presence or absence of Dox and Epo pre-treatment. Echocardiography demonstrated an improvement in fractional shortening (FS) in Epo-treated rats. Epo treatment was associated with a reduced mortality in both Epo-treated groups. Circulating EPC numbers were three times higher in Epo-treated compared with non-treated animals. Adhesive properties, migration, and tube formation capacity in matrigel of EPCs from both Epo-treated groups as compared with controls were significantly enhanced. EPC transfer to Dox-treated rats led to functional myocardial improvement equivalent to the protection afforded by treatment with Epo. In EPC obtained from humans, pre-incubation with Epo significantly attenuated the anti-proliferative and anti-migratory effects of treatment with Dox.. Epo treatment is potentially protective against myocardial dysfunction induced by Dox. These effects are partially mediated by enhancement in the number of EPC and their functional properties.

Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Cell Movement; Dinoprost; Doxorubicin; Echocardiography; Endothelial Cells; Erythropoietin; Male; Rats; Rats, Wistar; Recombinant Proteins; Stem Cells; Vasoconstrictor Agents

Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Doxorubicin; Erythropoietin; Humans

We describe the case of a 36-year-old woman with hereditary hemochromatosis (HH) resulting in end-stage cardiomyopathy and treated successfully with orthotopic cardiac transplantation. Before and after transplantation, the patient underwent aggressive treatment with frequent phlebotomy. We used erythropoietin concomitantly to maintain adequate hematocrit to support continued phlebotomy. We believe that aggressive use of phlebotomy provided the patient hemodynamic benefit and hastened the return of endocrine function post-transplantation. We also believe that the patient's history of high-dose vitamin C usage may have accelerated iron deposition in the heart and other vital organs.

Topics: Adult; Ascorbic Acid; Cardiomyopathies; Combined Modality Therapy; Contraindications; Erythropoietin; Female; Heart Transplantation; Hemochromatosis; Humans; Phlebotomy

The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required.

Topics: Age Factors; Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Canada; Cardiomyopathies; Cohort Studies; Comorbidity; Diabetes Mellitus; Echocardiography; Erythropoietin; Female; Hematocrit; Humans; Hyperlipidemias; Hyperparathyroidism; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Smoking; Survival Analysis; Systole