Improvement of cardiac performance by intravenous infusion of L-arginine in patients with moderate congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate the hemodynamic effect of L-arginine infusion in patients with congestive heart failure. BACKGROUND: Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. Nitric oxide, which was identified as endothelium-derived relaxing factor, is generated by nitric oxide synthase from L-arginine. Our hypothesis was that administration of L-arginine in patients with congestive heart failure may increase nitric oxide production and have a beneficial hemodynamic effect. METHODS: Twelve patients with congestive heart failure (New York Heart Association class II or III) due to coronary artery disease (left ventricular ejection fraction < 35%) were given 20 g of L-arginine by intravenous infusion over 1 h at a constant rate. Stroke volume, cardiac output and left ventricular ejection fraction were determined with Doppler echocardiography at baseline and at 30 and 60 min and 1 h after the end of infusion. Blood and urinary levels of nitrite/nitrate (NO2/NO3), stable metabolites of nitric oxide, were measured and clearance was calculated. RESULTS: One hour of infusion of L-arginine resulted in a significant increase in stroke volume (from 68 +/- 18 ml to 76 +/- 23 ml [mean +/- SD], p = 0.014) and cardiac output (from 4.07 +/- 1.22 liters/min to 4.7 +/- 1.42 liters/min, p = 0.006) without a change in heart rate. Mean arterial blood pressure decreased (from 102 +/- 11 mm Hg to 89 +/- 9.5 mm Hg, p < 0.002), and systemic vascular resistance decreased significantly. Within 1 h after cessation of L-arginine infusion, blood pressure, stroke volume, cardiac output and systemic vascular resistance were statistically not different from baseline values. Clearance of NO2/NO3 increased significantly during L-arginine administration (from 13.28 +/- 0.42 ml/min to 29.97 +/- 1.09 ml/min, p < 0.001). CONCLUSIONS: Infusion of L-arginine in patients with congestive heart failure results in increased production of nitric oxide, peripheral vasodilation and increased cardiac output, suggesting a beneficial hemodynamic and possibly therapeutic profile.

Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia.

OBJECTIVES: The purpose of this study was to explore interactions between paracrine angiotensin II (Ang-II) and tumor necrosis factor-alpha (TNF-alpha) during myocardial ischemia. BACKGROUND: Ischemic myocardium releases significant amounts of TNF-alpha. This paracrine release correlated with postischemic myocardial injury. Other studies showed myocardial protection obtained by the use of angiotensin-converting enzyme inhibitors (i.e., captopril) and the Ang-II type 1 receptor antagonist losartan after ischemia. The possibility that these agents decrease TNF-alpha synthesis has not yet been investigated. METHODS: Using the modified Langendorff model, isolated rat hearts underwent either 90 min of nonischemic perfusion (control group) or 1 h of global cardioplegic ischemia. In both groups, either captopril (360 micromol/liter) or losartan (182.2 micromol/liter) was added before ischemia. The hearts were assayed for messenger ribonucleic acid (mRNA) expression and effluent TNF-alpha levels. In addition, cardiac myocytes were incubated in cell culture with Ang-II. RESULTS: After ischemia, TNF-alpha mRNA expression intensified from 0.63 +/- 0.06 (control group) to 0.92 +/- 0.12 (p < 0.03), and effluent TNF-alpha levels were 711 +/- 154 pg/ml. The TNF-alpha mRNA expression declined to 0.46 +/- 0.07 (p < 0.01) and 0.65 +/- 0.08 (p < 0.02) in captopril- and losartan-treated hearts, respectively. Effluent TNF-alpha was below detectable levels. Concentrations of TNF-alpha in supernatants of incubated cardiac myocytes treated with 10 and 50 nmol/liter of Ang-II were 206.0 +/- 47.0 pg/ml and 810 +/- 130 pg/ml, respectively (p < 0.004). When pretreated with 700 micromol/liter of losartan, TNF-alpha was below detectable levels. CONCLUSIONS: This study presents an original explanation for previously reported myocardial protection after ischemia, obtained by the use of captopril and losartan. These drugs reduce TNF-alpha synthesis, providing strong evidence of active interactions between paracrine TNF-alpha and Ang-II in the evolution of the ischemic cascade.

The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study.

OBJECTIVES: This is a randomized controlled study of anemic patients with severe congestive heart failure (CHF) to assess the effect of correction of the anemia on cardiac and renal function and hospitalization. BACKGROUND: Although mild anemia occurs frequently in patients with CHF, there is very little information about the effect of correcting it with erythropoietin (EPO) and intravenous iron. METHODS: Thirty-two patients with moderate to severe CHF (New York Heart Association [NYHA] class III to IV) who had a left ventricular ejection fraction (LVEF) of < or =40% despite maximally tolerated doses of CHF medications and whose hemoglobin (Hb) levels were persistently between 10.0 and 11.5 g% were randomized into two groups. Group A (16 patients) received subcutaneous EPO and IV iron to increase the level of Hb to at least 12.5 g%. In Group B (16 patients) the anemia was not treated. The doses of all the CHF medications were maintained at the maximally tolerated levels except for oral and intravenous (IV) furosemide, whose doses were increased or decreased according to the clinical need. RESULTS: Over a mean of 8.2+/-2.6 months, four patients in Group B and none in Group A died of CHF-related illnesses. The mean NYHA class improved by 42.1% in A and worsened by 11.4% in B. The LVEF increased by 5.5% in A and decreased by 5.4% in B. The serum creatinine did not change in A and increased by 28.6% in B. The need for oral and IV furosemide decreased by 51.3% and 91.3% respectively in A and increased by 28.5% and 28.0% respectively in B. The number of days spent in hospital compared with the same period of time before entering the study decreased by 79.0% in A and increased by 57.6% in B. CONCLUSIONS: When anemia in CHF is treated with EPO and IV iron, a marked improvement in cardiac and patient function is seen, associated with less hospitalization and renal impairment and less need for diuretics.

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Proximal renal tubular acidosis: association with familial normaldosteronemic hyperpotassemia and hypertension.

Further investigation of a family with normaldosteronemic hyperpotassemia and low-renin hypertension showed seven members from three generations, who ranged in age from 4 to 56 years, to be affected. Results of earlier studies had established a normally functioning renin-aldosterone system and normal renal handling of potassium. Constant, albeit mild and asymptomatic, metabolic acidosis in all those affected prompted bicarbonate loading in both the propositus and his brother, which revealed a maximal renal tubular excretory capacity for bicarbonate reabsorption at serum levels of 18 mmole/liter and proved proximal renal tubular acidosis (PRTA). Further, a linear increase in urinary fractional potassium excretion accompanied that of bicarbonate in both, as in normal individuals. Dextrose-insulin infusion in the brother failed to reduce hyperpotassemia. These data support the hypothesis that a generalized cell membrane defect that specifically impedes potassium influx (as opposed to an isolated renal tubular defect) underlies this autosomal dominant disorder.

Familial hyperpotassemia and hypertension accompanied by normal plasma aldosterone levels: possible hereditary cell membrane defect.

Hypertension and hyperpotassemia that were accompanied by normal plasma aldosterone and low renin levels and were responsive to chlorothiazide administration were found in a 29-year-old patient and two decades later in his 21-year-old son. Their renal function is normal, including response to sodium sulfate, mannitol, and aldosterone infusions. Adrenal insufficiency was excluded. The renin-aldosterone system was proved intact by physiological and pharmacologic stress and angiotensin-II infusion. Also normal were values for blood counts, blood volumes, and erythrocyte and exchangeable body potassium. The postulation of a defective cell membrane impeding potassium influx is supported by the failure of glucose and insulin infusions to substantially reduce hyperpotassemia. In the context of a hereditary disorder (the pedigree, compatible with autosomal dominant inheritance, includes five affected in two generations), hypertension is a second phenotypic character of a single defective pleiotropic gene although its pathogenesis remains unclear.

Metformin enhances clearance of chylomicrons and chylomicron remnants in nondiabetic mildly overweight glucose-intolerant subjects.

OBJECTIVE: To assess the effect of metformin on the metabolism of intestinally derived lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant. RESEARCH DESIGN AND METHODS: A total of nine subjects with a BMI > or = 25 kg/m(2) and fasting serum glucose < or = 6.1 mmol/l and who were glucose intolerant were studied. The subjects underwent a vitamin A fat-loading test before and after a 3-month treatment with 850 mg metformin twice a day. The metabolic behavior of the postprandial lipoproteins was compared with that found in a group of 19 healthy normolipidemic individuals who participated in a previous study. RESULTS: Mean total plasma, chylomicron fraction, and nonchylomicron fraction retinyl palmitate (RP) pretreatment levels were 3.4-fold, 3.59-fold, and 3-fold higher, respectively, in the study group than in the normolipidemic group and were reduced by 50, 56, and 32%, respectively, after 3 months of metformin treatment. The decrease of chylomicron levels after treatment was positively correlated to the fasting triglyceride values before treatment (r = 0.73, P = 0.039) and to the serum insulin level at 120 min of standard glucose loading before treatment (r = 0.91, P = 0.002). CONCLUSIONS: Metformin was shown to be beneficial in the clearance of postprandial lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant.

Presence of insulin-renin-aldosterone-potassium interrelationship in normal subjects, disrupted in chronic hemodialysis patients.

The factors regulating aldosterone secretion in normals and in patients on chronic hemodialysis were studied by the determination of the circadian rhythm of plasma aldosterone, renin, cortisol, insulin, potassium, sodium, and glucose. Four normal volunteers and eight normotensive patients on regular dialysis treatment (RDT) were studied during prolonged recumbency on low sodium diet. A definite circadian rhythm for renin could not be demonstrated in RDT patients. The significant simple and multiple correlation coefficients found in normal subjects suggest that insulin participates in the regulation of aldosterone together with the other known factors: ACTH, renin, and potassium. In chronic renal failure, however, when basal conditions were maintained during prolonged recumbency, the correlations of insulin and renin with aldosterone were not found, suggesting that in this condition aldosterone secretion is controlled by ACTH and potassium. As a direct influence of insulin on aldosterone could not be demonstrated by multiple variance analysis, it seems that insulin is related to aldosterone indirectly through renin and/or potassium. The presence of significant correlations between insulin-potassium and potassium-aldosterone in RDT patients, without a significant insulin-aldosterone correlation, suggest that in the normals insulin participates in aldosterone regulation through renin secretion and not through potassium. A correlation between potassium and renin was not found in normals or in RDT patients.

Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

Anti-HIV indeterminate western blot in dialysis patients: a long-term follow-up.

In a group of 520 patients undergoing chronic hemodialysis, 23 (4. 4%) were enzyme immunoassay (EIA) positive for human immunodeficiency virus (HIV) and indeterminate by Western blot (IWB) analysis. The antibodies were mostly directed against p24 and p55 antigens. A comparison between hemodialysis patients with and without IWB showed significant differences between the two groups with respect to number of units of blood transfused, history of renal transplant rejection, and Rh status. No significant differences were observed with respect to ethnic group, nature of renal disease, duration of hemodialysis, associated diseases, and ABO blood group. The HIV IWB phenomenon may represent abnormal immune reactivity as a result of transplantation antigens and/or autoantibody formation. Five-year follow-up of the HIV EIA-positive IWB patients showed that none had seroconverted to HIV-positive status.

Sleep related breathing disorders are common contributing factors to the production of essential hypertension but are neglected, underdiagnosed, and undertreated.

There is now strong evidence from animal studies and, in humans, from epidemiological studies as well as from retrospective and prospective intervention studies, that obstructive sleep apnea (OSA) can cause persistent hypertension not only during sleep but during waking hours as well. There is also some evidence that habitual snoring alone, even without OSA, can do the same. Many of the hitherto unexplained epidemiological, clinical, biochemical, hematological, and physiological abnormalities seen in essential hypertension (EH) could be explained by the accompanying sleep related breathing disorders (SRBD). Many cases of resistant hypertension are probably due to SRBD. Recent studies show that SRBD are extremely common in EH but that the vast majority of patients with these sleep disorders are being missed by physicians who are treating the accompanying hypertension, even when the patients already have blatant symptoms of OSA. Recent investigations have shown that the probable reason for this underdiagnosis of OSA is lack of physician knowledge about the condition. This lack of knowledge is prevalent not only among family physicians, but among hypertension specialists and researchers in the field of hypertension as well. OSA is a common, easily diagnosed, and eminently treatable condition that is associated not only with disturbed sleep, loud snoring and excessive daytime sleepiness (which greatly increases the risk of traffic accidents), but also with hypertension, especially resistant hypertension, a broad range of cardiovascular problems, decreased sexual functioning, memory deficits, difficulty concentrating, and changes in personality and mood. It deserves much more attention by physicians treating hypertension than it is currently getting.

Glomerular basement membrane polyanion distribution and nitric oxide in spontaneous hypertensive rats: effects of salt loading and antihypertensive therapy with propranolol.

Cationic colloidal gold (CCG), a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, mainly heparan sulfate proteoglycan in spontaneous hypertensive rats (SHR) with or without salt loading and antihypertensive treatment with propranolol. The changes of mean GBM width and anionic sites distribution were assessed by electron microscopy. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO2) + nitrate (NO3), stable metabolites of NO. SHR had decreased NO production and increased GBM width (27%) compared with the control Wistar-Kyoto (WKY) rats. The chronic high dietary salt intake resulted in a significant increase in blood pressure, proteinuria, and renal function in the SHR rats. The chronic high salt dietary intake resulted in a decrease in NO in the WKY and a further reduction in NO production in the SHR. The GBM anionic sites count was similar in the SHR and WKY nonsalt-loaded groups, 13.5 +/- 0.5 and 12.8 +/- 0.4 CCG counts/microm GBM, respectively, but significantly lower in both salt-loaded SHR and WKY, 9.9 +/- 0.55 (P < .01) and 9.6 +/- 0.55 (P < .01) CCG counts/microm GBM, respectively. Antihypertensive treatment with propranolol in the salt-loaded SHR group resulted in lower blood pressure, a further decrease in NO production, but no significant changes in GBM width and anionic sites count. It is concluded that chronic high salt intake may be deleterious to the permselectivity of the GBM. A low NO production state that results from chronic salt loading in already hypertensive rats will result in more severe organ (renal) damage, most probably by the addition of the loss of GBM permselectivity to the existing pathomorphologic changes.

Postprandial intestinal-derived chylomicron and chylomicron remnants in essential hypertensive patients before and after prolonged captopril therapy.

The metabolism of the postprandial intestinal-derived lipoproteins, chylomicron and chylomicron remnants, is not known in patients with essential hypertension. After a fat meal, using the vitamin A test as a marker, retinyl palmitate was measured in the total plasma, chylomicron, and chylomicron remnant fractions in 14 untreated nondiabetic essential hypertensive patients with normal fasting lipids and lipoproteins. The vitamin A fat loading test was repeated in eight hypertensive patients after 3 months of captopril therapy. Fifteen matched normotensive subjects were used as controls. The untreated essential hypertensive patients had significantly higher chylomicron fraction concentration curves (AUC 17,469 +/- 2553 micrograms/L/h) P < .001 compared with the control group (AUC 13,208 +/- 1245 micrograms/L/h), by two-way analysis of variance with repeated measurements. After 3 months of captopril therapy, the chylomicron fraction (AUC 9701 +/- 1566 micrograms/L/h), and chylomicron remnants fraction (AUC 3487 +/- 580 micrograms/L/h) were much lower (P < .001) than before captopril therapy. Oral glucose tolerance tests were borderline in five of the eight hypertensives before captopril treatment but returned to normal after 3 months of therapy. In summary, postprandial intestinal-derived lipoprotein metabolism is altered in essential hypertensive patients. Captopril therapy caused significant improvement in the postprandial chylomicron metabolism.

Bezafibrate therapy in patients with isolated low high-density lipoprotein cholesterol levels may have a beneficial effect in prevention of atherosclerosis.

Although a low plasma high-density lipoprotein cholesterol (HDL-C) level is a well-accepted risk factor for coronary artery disease (CAD), it is unclear whether pharmacologic agents can effectively increase HDL-C levels and/or reduce the incidence of CAD in patients with isolated low HDL-C levels. An important determinant of HDL levels is the efficiency of postprandial lipoprotein catabolism. The purpose of the present study was to evaluate the efficacy of bezafibrate therapy in increasing HDL-C levels in these patients and to examine its effect on postprandial lipoprotein levels. Fasting and postprandial lipid and lipoprotein levels were studied in 23 patients with isolated low HDL-C levels before and during 3 and 6 months of bezafibrate treatment. Postprandial lipoprotein levels were evaluated using the vitamin A-fat loading test, in which these intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Patients with isolated low HDL had significantly higher levels of chylomicron RP than a control group of 19 normolipidemic subjects. The area below the chylomicron RP curve was 17,773 +/- 6,821 versus 13,936 +/- 6,217 micrograms/L.h, respectively (P < .005). No differences were found in chylomicron remnant levels between the groups. Bezafibrate therapy reduced the chylomicron RP area by 27%, from 17,773 +/- 6,821 to 12,895 +/- 2,576, and the nonchylomicron RP area by 25%, from 6,059 +/- 3,310 to 4,430 +/- 1,963 (P < .0001). It increased fasting HDL-C levels from 35 +/- 3 to 38 +/- 1.4 mg/dL after 3 months (P < .001) and to 40 +/- 2.2 mg/dL after 6 months (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolism of agmatine into urea but not into nitric oxide in rat brain.

Agmatine is a guanidino compound abundant in bacteria and plants where it serves as a precursor for polyamine synthesis. It can interfere with several neurotransmission-related functions and can exert neuroprotective effects after brain injury. Agmatine was recently identified in mammalian brain and its synthesis by arginine decarboxylation was characterized. Its metabolism by the brain is, however, unknown. Here we report evidence indicating that agmatine can be selectively metabolized in the rat brain (cerebellum) into urea and thus, may lead to formation of putrescine, the precursor of polyamine synthesis. In addition, while agmatine can inhibit brain nitric oxide synthase, it did not serve as a substrate for nitric oxide formation.

Intravenous iron for the treatment of predialysis anemia.

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.

Low-dose thiazides in the treatment of hypertension: benefits and risks in perspective.

Diuretics in low doses are very effective agents for controlling hypertension either where used alone or in combination. They have a marked cardioprotective effect, are the best tolerated of any anti-hypertensives and are at the same time the least expensive.

Avoiding the supine position during sleep lowers 24 h blood pressure in obstructive sleep apnea (OSA) patients.

Obstructive sleep apnea (OSA), is a common clinical condition affecting at least 2-4% of the adult population. Hypertension is found in about half of all OSA patients, and about one-third of all patients with essential hypertension have OSA. There is growing evidence that successful treatment of OSA can reduce systemic blood pressure (BP). Body position appears to have an important influence on the incidence and severity of these sleep-related breathing disturbances. We have investigated the effect of avoiding the supine position during sleep for a 1 month period on systemic BP in 13 OSA patients (six hypertensives and seven normotensives) who by polysomnography (PSG) were found to have their sleep-related breathing disturbances mainly in the supine position. BP monitoring was performed by 24-h ambulatory BP measurements before and after a 1 month intervention period. We used a simple, inexpensive method for avoiding the supine posture during sleep, namely the tennis ball technique. Of the 13 patients, all had a reduction in 24-h mean BP (MBP). The mean 24-h systolic/diastolic (SBP/DBP) fell by 6.4/2.9 mm Hg, the mean awake SBP/DBP fell by 6.6/3.3 mm Hg and the mean sleeping SBP/DBP fell by 6.5/2.7 mm Hg, respectively. All these reductions were significant (at least P < 0.05) except for the sleeping DBP. The magnitude of the fall in SBP was significantly greater in the hypertensive than in the normotensive group for the 24 h period and for the awake hours. In addition, a significant reduction in BP variability and load were found. Since the majority of OSA patients have supine-related breathing abnormalities, and since about a third of all hypertensive patients have OSA, avoiding the supine position during sleep, if confirmed by future studies, could become a new non-pharmacological form of treatment for many hypertensive patients.

Sector retinitis pigmentosa in juvenile nephronophthisis.

In a patient with juvenile nephronophthisis, sector retinitis pigmentosa was found as an extrarenal manifestation, establishing a hitherto undescribed variety of retinal degeneration occurring in this disorder. The retinal function in this case was identical with that in the classic type of sector retinitis pigmentosa, namely, subnormal ERG amplitudes but normal cone and rod implicit times. The range of the retinal findings and their autosomal recessive transmission are discussed. Paucity of information makes it difficult to elucidate the basic genetic defect operating in this condition.

Correction of anemia in patients with congestive heart failure increases resting energy expenditure.

BACKGROUND & AIM: Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF. PATIENTS AND METHODS: Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls. RESULTS: After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively). CONCLUSION: Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake.