losartan-potassium and Arrhythmias--Cardiac

Current evidence suggests that erythropoiesis-stimulating agents (ESAs), including erythropoietin and darbepoetin, may have a direct cardio-protective effect. However, randomized controlled trials (RCTs) assessing the efficacy and safety of ESAs in patients with acute ST-segment elevation myocardial infarction (STEMI) have yielded heterogeneous results. Here, we performed a meta-analysis of RCTs to assess whether the administration of ESAs can improve cardiac functional parameters, such as left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV), and attenuate infarct size in patients with acute STEMI.. The PubMed, EBSCO, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for relevant RCT studies on ESAs published before May 13, 2011. A total of nine RCTs involving 1,244 participants were identified. The original data of these studies were aggregated using fixed effect models. Compared with controls, the administration of ESAs showed a slight but significant improvement in LVEF (1.38%; 95% confidence interval 0.38-2.37%; p = 0.007). However, no significant improvement in LVEDV, LVESV, and infarct size was observed, and no increase in all-cause severe adverse effect was indicated.. Our meta-analysis indicates that the superiority of ESAs over conventional therapy in patients with acute STEMI is limited using current procedures. However, there is evidence to suggest that the timing and dosing of ESA administration may be optimized. Moreover, the long-term cardio-protective effect of ESAs in this patient population may be beneficial and worth exploring.

Topics: Arrhythmias, Cardiac; Cardiac Output; Cardiotonic Agents; Darbepoetin alfa; Electrocardiography; Erythropoiesis; Erythropoietin; Hematinics; Humans; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Recombinant Proteins

Arrhythmia is the foremost cause of sudden death after myocardial infarction (MI). Animal models have recently shown that erythropoietin (EPO) can reduce the incidence of arrhythmia after MI.. We investigated the effects of administrating 33,000 IU EPO on the occurrence of post-MI arrhythmia in 40 patients with ST-elevation MI who were randomly assigned in either EPO or placebo groups. Arrhythmias were blindly documented using full 12-lead configuration during 24 hours after percutaneous coronary intervention (PCI) by a cardiologist. Afterward, CK-MB, hematologic, and hemodynamic data were examined within 2 weeks after MI.. A comparison made between the 2 groups showed significant differences in the incidence of arrhythmias (20% in EPO group and 35% in placebo group, P = 0.043). However, no significant differences in type of arrhythmias were observed between the groups. There was no significant difference between levels of CK-MB in the 2 groups during 24 hours (P = 0.186). Hematologic and hemodynamic data showed no significant changes 2 weeks after PCI.. High-dose administration of EPO in patients with ST-elevation MI who have been treated by primary PCI and standard antiplatelet therapy reduces the occurrence of arrhythmias. For clinical interpretation of the results, further well-designed trials are required.

Topics: Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Biomarkers; Creatine Kinase, MB Form; Electrocardiography; Erythropoietin; Female; Hemodynamics; Humans; Iran; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

Topics: Animals; Apoptosis; Arrhythmias, Cardiac; Erythropoietin; Male; Mitochondria; Mitochondrial Dynamics; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Rats, Wistar

Erythropoietin (EPO) is a potent cardioprotective agent in models of myocardial ischemia and reperfusion (I/R). It has been suggested recently that EPO may also reduce ventricular arrhythmia after I/R. The present study investigated the role of neuronal nitric oxide synthase (nNOS) on the antiarrhythmic effects of EPO. EPO treatment increased nNOS expression in isolated neonatal mouse ventricular myocytes. Cotreatment with the phosphatidylinositol 3 (PI3)-kinase inhibitor, LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride], or treatment of cardiomyocytes infected with a dominant negative adenovirus targeted to Akt1 (ADV-dnAkt1) blocked the effects of EPO on nNOS expression, suggesting that EPO regulates nNOS expression via PI3-kinase and Akt. To examine the in vivo antiarrhythmic effects of EPO, wild-type (WT) and nNOS(-/-) mice were anesthetized and, after a baseline measurement, subjected to myocardial I/R to provoke ventricular arrhythmias. Pretreatment with EPO 24 h before ischemia increased nNOS expression and significantly reduced the number of premature ventricular contractions (PVCs) and the incidence of ventricular tachycardia (VT) in WT mice. In contrast, treatment with EPO had no effect on PVCs or the incidence of VT in nNOS(-/-) mice. Furthermore, EPO treatment after ischemia significantly reduced the threshold dose of cesium chloride (CsCl) to induce VT. We conclude that EPO via nNOS protects the heart from spontaneous and CsCl-induced ventricular arrhythmia during myocardial I/R.

Topics: Animals; Arrhythmias, Cardiac; Cells, Cultured; Cesium; Chlorides; Electrocardiography; Enzyme Inhibitors; Erythropoietin; Gene Expression; Heart; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Nitric Oxide Synthase Type I; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Tachycardia, Ventricular; Ventricular Premature Complexes

To explore the effect of erythropoietin (EPO) on reperfusion arrhythmias in rats and identify the possible mechanism involved.. Forty-five SD rats were randomized into a sham-operated group and 4 cardiac ischemia/reperfusion (IR) injury groups, which were further divided into IR group, LY294002 group, EPO group, and EPO+LY294002 group. Cardiac IR injury was induced in the 4 IR injury groups by ligating the left anterior descending branch of the coronary artery (LAD) for 30 min followed by reperfusion for 3 h, with subsequent treatments accordingly. The occurrence of arrhythmias was monitored and scored during experiment, and the levels of serum CK-MB and cTnI were detected. The content of MDA in the myocardium was determined by thiobarbituric acid (TBA) method, and the content of SOD by xanthine oxidase method.. The arrhythmia score in EPO group was significantly lower than those in IR, LY294002 and EPO+ LY294002 groups (P<0.05). The levels of serum CK-MB and cTnI were significantly lower in EPO group than in the other 3 IR groups (P<0.001). The EPO group showed also significantly lower MDA content (P<0.001) and higher SOD content than the other 3 IR groups (P<0.001).. EPO at the dose of 1000 mg/kg decreases the incidence of reperfusion arrhythmias in rats, and this effect can be attenuated by LY294002 pretreatment, suggesting that the cardioprotective effect of EPO involves antioxidation mediated by the phosphoinositide 3-kinase (PI3K) pathway.

Topics: Animals; Arrhythmias, Cardiac; Chromones; Coronary Occlusion; Erythropoietin; Female; Male; Morpholines; Myocardial Reperfusion Injury; Phosphatidylinositol 3-Kinases; Random Allocation; Rats; Rats, Sprague-Dawley

Topics: American Heart Association; Anemia; Arrhythmias, Cardiac; Catheter Ablation; Chicago; Darbepoetin alfa; Erythropoietin; Heart Failure; Hematinics; Humans; Mesenchymal Stem Cell Transplantation; Myoblasts, Skeletal; Myocardial Infarction; Quality of Life; Stroke Volume

Juvenile hemochromatosis is a rare genetic disorder that causes iron overload. Clinical complications, which include liver cirrhosis, heart failure, hypogonadotropic hypogonadism and diabetes, appear earlier and are more severe than in HFE-related hemochromatosis. This disorder, therefore, requires an aggressive therapeutic approach to achieve iron depletion. We report here the case of a young Italian female with juvenile hemochromatosis who was unable to tolerate frequent phlebotomy because of coexistent ss-thalassemia trait. The patient was successfully iron-depleted by combining phlebotomy with recombinant human erythropoietin.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Arrhythmias, Cardiac; beta-Thalassemia; Chelation Therapy; Chromosomes, Human, Pair 1; Deferoxamine; Erythropoietin; Estrogen Replacement Therapy; Female; Hemochromatosis; Hemosiderosis; Hormone Replacement Therapy; Humans; Hypogonadism; Liver Cirrhosis; Phlebotomy; Progesterone; Recombinant Proteins

Topics: Adult; Aged; Aged, 80 and over; Anemia; Angina Pectoris; Arrhythmias, Cardiac; Drug Evaluation; Erythropoietin; Female; Follow-Up Studies; Humans; Immunologic Factors; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Arrhythmias, Cardiac; Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Pericarditis; Quality of Life; Renal Dialysis; Sick Sinus Syndrome