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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intensive iron therapy is now a generally accepted adjunct for the treatment of renal anemia with recombinant human erythropoietin. However, with the emerging role of iron in cardiovascular disease, carcinogenesis, infectious diseases, and other disorders, it is no longer appropriate to assume that any amount of stored iron is safe until proven otherwise. In this article, the history and current status of the "iron hypothesis" on ischemic heart disease are briefly reviewed, followed by comments on iron management practices for renal patients.
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PMID:Iron therapy and cardiovascular disease. 1008 98

AIDS has created considerable concern among the public regarding being transfused with potentially infectious blood. However, autologous blood donations are still not maximally provided nor utilized. Significant heart disease disqualifies all allogeneic and most autologous blood donors (American Association of Blood Banks (AABB) Standards 1994). Disqualification is based on the widespread belief that donating blood could possibly be detrimental to their health. However, this belief has not been sufficiently documented. Sixty-eight donors (ages 14-84 years), all with histories of significant cardiac diseases, donated 111 units of whole blood (1-3 units). Twenty-eight patients donated 1 unit, 37 donated 2 units, and three patients donated 3 units. Fifty-nine patients had ischemic heart disease, and nine had valvular heart disease (five with mitral stenosis and four with mitral valve prolapse). No patient received erythropoietin, and only one received equal volume replacement with normal saline during donation. All these patients eagerly wished to donate in spite of being informed of the possible complications. No patient wishing to donate has been refused, and none has experienced any adverse consequences from donating. Forty-four patients underwent total hip/knee replacements. Only 56 units (50%) were transfused to 37 patients (54%). Although our experience is limited, it appears that many patients with histories of well established cardiac diseases can easily tolerate donating blood without compromising their health.
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PMID:Should cardiac disease prevent autologous blood donation? 1017 96

Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix transcription factor that plays essential roles in mammalian development and physiology. HIF-1 is a heterodimer composed of HIF-1alpha and HIF-1beta subunits. The expression and activity of the HIF-1alpha subunit are tightly regulated by cellular O2 concentration. Under hypoxic conditions, HIF-1 activates the transcription of genes encoding erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase O2 delivery or facilitate metabolic adaptation to hypoxia. HIF-1 is essential for embryonic vascularization and survival, neovascularization in ischemic myocardium, hypoxia-induced pulmonary vascular remodeling, and tumor vascularization. HIF-1alpha is overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia.
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PMID:Expression of hypoxia-inducible factor 1: mechanisms and consequences. 1060 34

The pathogenesis of hypertension in haemodialyzed uraemic patients is multifactorial. The following are involved: sodium and water retention as a result of the impaired excretory capacity of the kidneys, excessively increased activity of the RAAS and sympathetic nerve, increased levels of the vascular constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and reduced formation of vasodepressor factors. As to other factors in the development of hypertension raised intracellular calcium associated with hyperparathyroidism may participate, the stiffness of calcified arteries, erythropoietin treatment and preexisting essential hypertension. Treatment comprises salt restriction below 5 g/day, systematic control of the volume of extracellular fluid by ultrafiltration during every haemodialysis to the level of so-called dry weight and pharmacological treatment in patients where volume control dos not suffice. All drug groups are used. In their selection contraindications are taken into consideration as well as co-morbidity, the dialyzability of antihypertensive drugs and compelling evidence. In patients with a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta-blockers are indicated in patients with IHD, in particular after IM. Calcium blockers are recommended in ventricular hypertrophy and diastolic dysfunction, when beta-blockers are contraindicated and in elderly patients. ACEI indicated in congestive heart failure and left ventricular hypertrophy with systolic dysfunction. Inhibitors of AT1 receptors are an alternative in case of undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used mainly in combinations. In case of failure the haemodialyzation method can be altered or changing the patients to CAPD may be considered. The relationship between BP and the survival of haemodialyzed patients is bimodal. An adverse effect is exerted by a high as well as low BP and in particular by interdialyzation hypotension. The target BP for the haemodialyzed population has not been defined so far. There is, however, evidence that a high BP is independently associated with the de novo development of IHD and MAP above 106 mm Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes the development and progression of left ventricular hypertrophy and MAP below 106 mm Hg the development of heart failure. Long-term survival for 15 and more years is statistically significantly associated with MAP lower than 99 mm Hg.
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PMID:[Hypertension in hemodialyzed uremic patients]. 1095 54

Cardiac diseases account for almost 50% of deaths in long-term dialysis patients. Left ventricular dysfunction is present in approximately 80% of these patients and is highly predictive of future ischemic heart disease, cardiac failure, and death. Anemia has been identified as one of several risk factors responsible for cardiac complications. Cardiovascular consequences of renal anemia begin relatively early in the course of renal failure and progress with the decline of renal function and also during dialysis therapy. In chronic renal failure patients with severe anemia (hemoglobin levels <10 g/dL), increased cardiac output, high left ventricular mass, left ventricular end-diastolic and end-systolic diameters, and cardiac symptoms improve after partial correction of anemia (hemoglobin levels >11 g/dL according to the European Best Practice Guidelines). It is disappointing that normalization of hemoglobin levels has only minor effects with respect to regression of left ventricular hypertrophy and left ventricular dilation. There is no benefit of hemoglobin normalization on all-cause mortality of dialysis patients or on survival of end-stage renal disease patients with congestive heart failure or ischemic heart disease. Therefore, prevention of renal anemia may be more efficient than its treatment. Hypertension is one of the major side effects of recombinant human erythropoietin (rHuEPO) therapy. Multiple factors are involved in rHuEPO-induced hypertension. High blood pressure can usually be controlled readily in the majority of the patients.
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PMID:Effect of erythropoietin on cardiovascular diseases. 1157 16

Cardiovascular disease is the major cause of death among patients with end-stage renal disease, accounting for almost half of all fatalities. In recent years much progress has been made in understanding the pathogenesis of cardiovascular disease in the uraemic population. Anaemia is a consistent finding in chronic renal disease, affecting up to 90% of patients, and the central role of anaemia in the development of cardiovascular dysfunction is now well established. A significant proportion of patients have established cardiovascular complications on initiation of dialysis, raising the possibility of early correction of anaemia as a strategy for preventing cardiovascular co-morbidities among renal patients. Randomized, controlled trials have shown that normalization of haemoglobin (Hb) with recombinant erythropoietin (rh-Epo) is of no cardiovascular benefit in haemodialysis patients with symptomatic heart failure, ischaemic heart disease, or severe left ventricular dilatation, although suggestive evidence exists for benefits at earlier stages of cardiac disease. Results from large-scale clinical trials are required to clarify the effects of early anaemia correction on mortality and cardiovascular function, as well as appropriate treatment targets in different patient populations. The potential exists for higher Hb levels to extend patient survival through cardioprotective effects.
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PMID:Anaemia in chronic renal disease: lessons learned since Seville 1994. 1159 Feb 56

Intramyocardial injection of genes encoding angiogenic factors could provide a useful approach for the treatment of ischemic heart disease. However, uncontrolled expression of angiogenic factors in vivo may cause some unwanted side effects, such as hemangioma formation, retinopathy, and arthritis. It may also induce occult tumor growth and artherosclerotic plaque progression. Because hypoxia-inducible factor 1 is up-regulated in a variety of hypoxic conditions and it regulates gene expression by binding to a cis-acting hypoxia-responsive element (HRE), we propose to use HRE, found in the 3' end of the erythropoietin gene to control gene expression in ischemic myocardium. A concatemer of nine copies of the consensus sequence of HRE isolated from the erythropoietin enhancer was used to mediate hypoxia induction. We constructed two adeno-associated viral vectors in which LacZ and vascular endothelial growth factor (VEGF) expressions were controlled by this HRE concatemer and a minimal simian virus 40 promoter. Both LacZ and VEGF expression were induced by hypoxia and/or anoxia in several cell lines transduced with these vectors. The functions of these vectors in ischemic myocardium were tested by injecting them into normal and ischemic mouse myocardium created by occlusion of the left anterior descending coronary artery. The expression of LacZ gene was induced eight times and of VEGF 20 times in ischemic myocardium compared with normal myocardium after the viral vector transduction. Hence, HRE is a good candidate for the control of angiogenic factor gene expression in ischemic myocardium.
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PMID:Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model. 1208 14

Despite the use of recombinant human erythropoietin (rh-EPO, epoetin) for more than a decade in treating renal anaemia, there is still considerable debate over optimal target haemoglobin (Hb) levels. Current European and North American guidelines that are based on decade-old trials aim for partial anaemia correction, with a subnormal target Hb concentration. More recent randomized clinical trials examining the effect of normalizing Hb levels have produced conflicting results. A study in the USA, in patients with existing congestive heart failure or ischaemic heart disease, showed an unexpected rise in cardiac mortality and haemodialysis access failure with higher Hb levels. In contrast, three other studies (in Australia, Spain and Canada) that normalized Hb levels in healthier dialysis patients observed improvements in quality of life and exercise capacity and a slower progression of left ventricular dilatation, without an unacceptable increase in the incidence of adverse effects. These studies indicate that, while higher Hb levels may be detrimental to patients with pre-existing cardiac disease, healthier patients benefit from normalized Hb levels. Thus, there is no clear scientific rationale for setting a single Hb target for all patients, and individualized treatment targets would appear to be a more logical and patient-centred approach.
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PMID:A rationale for an individualized haemoglobin target. 1209 94

Erythropoietin (Epo) is a hormone regulating proliferation and differentiation of erythroid cells. The hypothesis that hematopoietic and endothelial cells share a common hemangioblast progenitor among others is based on the finding that both cell lineages express cell surface antigens like CD31 and CD34. In this study we investigated the angiogenic potential of recombinant human erythropoietin (rHuEpo) on endothelial cells derived from human adult myocardial tissue. In addition, we compared the angiogenic potential of rHuEpo to that of other cytokines (VEGF, aFGF) and combinations of growth factors. Samples of myocardial tissue (cardiac auricle) were obtained during coronary bypass surgery, embedded in a fibrin gel matrix, and cultured for 21 days. Capillary sprouting was measured with an eye-piece graticule under an inverted-phase contrast microscope. Tube-forming endothelial cells were characterized by immunohistochemistry and RT-PCR. Using a concentration of 2.5 U/ml, we found that rHuEpo stimulates capillary outgrowth up to 220%, compared to the nonstimulated physiological outgrowth. Epo therefore exhibits the same angiogenic potential on endothelial cells in our in vitro assay as VEGF(165) (230% increase). Erythropoietin stimulates capillary outgrowth in an in vitro angiogenesis assay using adult human myocardial tissue. This implies a role of erythropoietin in vasoproliferative processes. rHuEpo may serve as a direct angiogenic substance in patients with ischemic heart disease.
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PMID:Erythropoietin and VEGF exhibit equal angiogenic potential. 1220 56

Left ventricular (LV) volume and pressure overload occur frequently in chronic kidney disease (CKD). Anemia is a risk factor for left ventricular hypertrophy (LVH) and dilatation, heart failure, and death. Normalization of hemoglobin with erythropoietin may prevent LVH and dilatation in CKD, but in patients in later phases of their cardiac disease, this intervention is not of benefit. Increased vascular volume causes hypertension, which in turn causes LVH, cardiac failure, and ischemic heart disease (IHD). Manifestations of arteriosclerosis are associated with adverse cardiac outcomes, and angiotensin converting enzyme (ACE) inhibitors may improve LVH and markers of arteriosclerosis. Aortic stenosis in dialysis patients occurs infrequently, but may deteriorate rapidly. The hemodialysis milieu is the quintessential model of LV overload cardiomyopathy.
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PMID:Hemodynamic cardiovascular risk factors in chronic kidney disease: what are the effects of intervention? 1264 77


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