Atrial natriuretic peptide is not degraded by the lungs in humans.

In an attempt to identify and quantify the sites of atrial natriuretic peptide (ANP) degradation, particularly the lungs, a new tracer method to study ANP metabolism in vivo in humans was developed and applied to patients with left ventricular dysfunction. Thirteen male, normotensive, cardiac patients with different degrees of left ventricular myocardial involvement were enrolled in the study. The study protocol required constant infusion (3 patients) or bolus injection (10 patients) of 125I-labeled ANP just upstream of the right atrium and blood sampling from different sites (pulmonary artery, aorta, inferior vena cava, and femoral vein) during the hemodynamic study. Data analysis was based on a kinetic model consisting of three blocks in series (right heart, lungs and left heart, and periphery) supplied by the same plasma flow (plasma cardiac output). Plasma levels of native ANP were measured with a sensitive and specific immunoradiometric assay method. ANP values measured in the aorta (163.9 +/- 144.8 pg/mL, n = 80) were superimposable on those measured in the pulmonary artery (161.8 +/- 136.5 pg/mL, n = 80). Negligible extraction of 125I-labeled ANP was found in the lungs and left heart block (on average 0.08 +/- 3.92%), whereas the peripheral block extraction (46.2 +/- 7.8%) accounted for almost total hormone removal from the blood (whole body extraction was 46.4 +/- 6.6%). ANP metabolic clearance rate (3.11 +/- 1.48, range 1.4-6.8 L/min) declined with the progression of left ventricular dysfunction (plasma cardiac output 3.46 +/- 1.08, range 1.2-5.7 L/min), and a close correlation between metabolic clearance rate and cardiac output was evident. Our data suggest that lungs do not extract, or extract only very small amounts, of labeled ANP administered iv to patients with different degrees of left ventricular myocardial involvement, and whole body extraction of labeled ANP remains relatively stable with the progression of disease, and the large reductions in clearance values observed in our patients can be ascribed mainly to the reductions in cardiac output.

Circulating levels of cardiac natriuretic peptides (ANP and BNP) measured by highly sensitive and specific immunoradiometric assays in normal subjects and in patients with different degrees of heart failure.

Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels increase in patients with heart failure with the progression of clinical symptoms and with the deterioration of hemodynamics; consequently, assay methods for these peptides may be useful in the follow-up of cardiac patients. Non-competitive immunoradiometric assay (IRMA) methods for ANP or BNP do not generally require preliminary extraction and/or purification of the plasma sample, and so may be more suitable than competitive immunoradiometric assay (RIA) methods for the routine assay of plasma peptide concentrations. We evaluated the analytical characteristics and clinical usefulness of two IRMAs for plasma ANP and BNP, to verify whether these methods may be considered suitable for the follow-up of patients with heart failure. Both methods are based on the solid-phase sandwich IRMA system, which uses two monoclonal antibodies prepared against two sterically remote epitopes of peptide molecule; the first antibody was coated on the beads solid-phase and the second was radiolabeled with 125I. Blood samples were collected from a brachial vein in ice-chilled disposable polypropylene tubes containing aprotinin and EDTA after the patient had rested for at least 20 min in the recumbent position. Plasma samples were immediately separated by centrifugation and stored at -20 C until assay. The IRMA methods showed a better sensitivity and a wider working range sensitivity (about 2 ng/l) than those of RIA methods. Moreover, the normal range found with these methods (ANP = 16.1 +/- 8.6 ng/l, 5.2 +/- 2.8 pmol/l, BNP = 8.6 +/- 8.2 ng/l, 2.5 +/- 2.4 pmol/l) was similar to that generally reported using the most accurate methods, such as the other IRMAs or RIAs, using a preliminary extraction and purification of plasma samples with chromatographic procedures. Our results obtained in patients with different degrees of heart failure indicate that plasma ANP and BNP increase with the progression of clinical symptoms (NYHA class) (ANOVA p < 0.0001). Indeed, circulating levels of ANP (R = -0.701, no. = 86) and BNP (R = -0.745, no. = 55) were significantly (p < 0.0001) and negatively correlated with the left ventricular ejection fraction values. Furthermore, a close curvilinear regression (R = 0.960, no. = 215) was found between ANP and BNP values, because plasma BNP progressively increases more than plasma ANP in patients with different stages of heart failure. In conclusion, IRMA methods are preferable for the measurement of plasma ANP and BNP for experimental studies and routine assay because they are more practicable, sensitive and accurate than RIA procedures. Finally, BNP assay appears to be better than ANP for discriminating between normal subjects and patients with different degrees of heart failure.

Evidence that atrial natriuretic peptide tissue extraction is not changed by large increases in its plasma levels induced by pacing in humans.

Atrial natiurectic peptide (ANP) is a cardiac hormone with a very short plasma half-life, which plays an important role in a variety of clinical conditions associated with an increase in pressure and/or volume overload on the heart. The MCR of the hormone is considered to represent a stable parameter, reflecting the uptake and degradation rate of ANP by the periphery, only scarcely affected by rapid oscillations of circulating levels. To evaluate the extent to which MCR is affected by rapid and large variations of circulating levels of the hormone, we measured MCR in five patients with different degrees of myocardial function (from normal to severely impaired), in whom changes in ANP levels were induced by atrial and/or ventricular pacing. Cardiac output was simultaneously measured by thermodilution to calculate whole body extraction of ANP. During constant i.v. infusion of [125I]ANP, the hormone MCR was determined both under basal conditions (at tracer equilibration, 20-30 min after the start of infusion) and during atrial and ventricular pacing. Pacing maneuvers, begun 50 min after the start of infusion, induced a marked and rapid increase in endogenous plasma ANP values in all patients (on the average, 3,7-fold compared to basal values; range, 1.8-5.68), whereas corresponding values of [125I]ANP only minimally changed. The MCR of ANP (3.62 +/- 1.06 L/min, mean +/- SD) slightly decreased (by repeated measures ANOVA, P = 0.0458) during atrial and ventricular pacing procedures (3.35 +/- 1.03 and 3.15 +/- 0.74 L/min, respectively), reaching a mean value of 88.7 +/- 9.0% compared to basal. The small decrease in MCR could be almost completely ascribed to hemodynamic factors; indeed, basal cardiac output (5.76 +/- 1.70 L/min) was found, on the average, to be slightly decreased during atrial and ventricular pacing (5.28 +/- 1.46 and 5.16 +/- 1.33 L/min, respectively), and so whole body extraction of the hormone, measured before pacing (50.0 +/- 12%), remains stable throughout the study period (50.4 +/- 10.6% and 49.6 +/- 10% during atrial and ventricular pacing, respectively). Our findings demonstrate that degradative mechanisms involved in ANP clearance are not saturable at least for acute elevations of ANP plasma levels up to 3-5 times the basal level.

Analytical performance and clinical usefulness of a commercially available IRMA kit for measuring atrial natriuretic peptide in patients with heart failure.

We evaluated the analytical characteristics and clinical usefulness of a commercially available IRMA kit for measuring plasma concentrations of atrial natriuretic peptide (ANP) in healthy subjects and in patients with heart failure. The method uses two monoclonal antibodies prepared against sterically remote epitopes of the ANP molecule; the first antibody is coated on the solid-phase beads, and the second is radiolabeled with 125I. Fifty-nine healthy subjects and 77 patients with heart failure were studied. After subjects had rested 20 min in a recumbent position, blood samples were collected from a brachial vein into ice-chilled disposable polypropylene tubes containing aprotinin and EDTA. Plasma samples were immediately separated by centrifugation and stored at -20 degrees C until assay. The working range (CV <15%) was 10-2000 ng/L. The detection limit (2.13 +/- 0.91 ng/L) was similar to those reported for other IRMAs but was much better than those of RIAs. For healthy subjects, the results of this method (18.0 +/- 10.6 ng/L, range 4.7-63 ng/L, median 16.7 ng/L, n = 59) were similar to those generally reported for the most accurate methods, i.e., those using preliminary extraction and chromatographic purification of plasma samples. Measured plasma ANP was significantly associated with the severity of clinical symptoms, i.e., NYHA class (ANOVA, P <0.0001), and with the left ventricular ejection fraction (n = 62, r = 0.618, P <0.0001). Patients with severe heart failure showed greatly increased values (NYHA III-IV: 257.4 +/- 196.6 ng/L, n = 23).

Preparation of mono-radioiodinated tracers for study of the in vivo metabolism of atrial natriuretic peptide in humans.

In the present paper we evaluate the optimum chemical conditions for labelling atrial natriuretic peptide (ANP) and its metabolites and for preparing highly purified radiotracers which can be used for in vivo kinetic studies of ANP in humans. Synthetic alpha h1-28ANP and some hormone metabolites were iodinated with Na125I or Na131I by means of the lactoperoxidase (ANP) or the chloramine-T (ANP metabolites) technique. The biological activity of labelled ANP was tested by means of a binding study using mouse cardiac membranes. A high-performance liquid chromatography (HPLC) procedure was used to purify the labelled hormone and the principal labelled metabolites in venous plasma samples collected up to 50 min after the injection of 125I-labelled ANP from nine healthy men. The main ANP kinetic parameters were derived from the disappearance curves of the [125I]ANP, which were satisfactorily fitted by a biexponential function in all subjects. The main advantages of this tracer technique are: (1) high accuracy, allowing the identification of the metabolites produced in vivo under steady-state conditions after injection of the precursor (labelled hormone); (2) high sensitivity, allowing the detection of minimal quantities of metabolites (that cannot be identified on the basis of the integrated areas from the ultraviolet-absorbing peaks on HPLC); (3) high specificity, allowing the detection of possible in vitro artefactual generation of cleavage products of ANP using an internal labelled standard. Utilizing this tracer method, it was possible to estimate the principal parameters of ANP kinetics and also to plot the appearance curves of the labelled metabolites produced in vivo after the injection of the labelled precursor.

In vivo measurement of ANP overall turnover and identification of its main metabolic pathways under steady state conditions in humans.

Using a tracer method, we evaluated, in vivo, the main turnover parameters and the main metabolic pathways of ANP in 10 normal subjects. HPLC was used to purify the labeled hormone and the principal labeled metabolites present in venous plasma samples collected at determined times after tracer injection. The main ANP kinetic parameters were derived from the disappearance curves of [125I] ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large, plasma equivalent space (10.9 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this space due to both degradation and to distribution in peripheral spaces. The mean residence time in the body (19.4 +/- 19.8 min) and the plasma equivalent total distribution volume (28.2 +/- 11.5 l/m2) indicate that ANP is also widely distributed outside the initial space in humans (circulating ANP is no more than 1/15 of the body pool). Metabolic clearance rate values were distributed across a wide range (from 740 ml/min/m2 to 2581 ml/min/m2, mean 1849 ml/min/m2), and were shown to strongly correlate (R = 0.962) with the daily urinary excretion of sodium. A complete separation of labeled ANP from its labeled metabolites was achieved by the HPLC technique; at least 3 different peaks due to labeled metabolites in vivo produced from the injected [125I]ANP1-28 were found. The first chromatographic peak eluted showed an identical elution time to monoiodotyrosine. At least two other peaks due to in vivo generated labeled metabolites were well identified in the chromatograms: one peak (coeluting with labeled COOH-terminal tripeptide, H-Phe-Arg-Tyr-OH) was eluted ahead and one (coeluting with labeled peptide fragments ANP7-28, ANP13-28, and ANP18-28) behind the elution peak of the labeled ANP. The peak of labeled tyrosine appearing in the plasma ranged between 3 and 5 min after tracer injection; the other two peaks of radioiodinated metabolites showed their highest activity in the first sample (1.5 min), suggesting an earlier occurrence of their peaks. These labeled metabolites seem to be intermediate peptides, between the intact circulating form of the hormone and the final labeled metabolite (tyrosine), which is the last amino acid of the peptide hormone, produced in vivo after injection of the tracer.(ABSTRACT TRUNCATED AT 400 WORDS)

Critical evaluation of endothelins assay.

Endothelin(s) is (are) generally measured by highly-sensitive RIA (radioimmunoassay) or sandwich-EIA (enzyme immunoassay) methods after preliminary extraction and chromatographic purification using Sep-Pak C18 cartridges; however, there is no general consensus about the range of endothelin circulating levels in healthy subjects and patients. We have evaluated the analytical performance of two commercial RIAs for plasma endothelin-1 assay (supplied by Peninsula Laboratories, Belmont, California, and by Biomedica Gruppe, Biomedica Gesellschaft mbH, Vienna, Austria) in order to verify whether differences in extraction procedures, antibody affinities or standard preparations can explain the different results obtained by these two RIAs. The RIA kits tested in the present study showed some differences in the analytical performance; in particular, different antibody specificities have been observed. The concentration range of endothelin(s) assayed with an imprecision better than 15%, which can be considered the working range, was wider for the Peninsula than for the Biomedica kit (i.e. from 1.6 to 50 fmol/tube vs 0.7 to 10 fmol/tube), whereas the two RIA kits showed similar sensitivity (i.e. about 0.2 fmol/tube). Taking into account the working range and sensitivity of the two RIAs to measure with an acceptable error the samples of normal subjects and the most part of patients, > or = 3-ml volumes of plasma must be extracted by Sep-Pak C18 cartridges and then measured by RIA. Owing to the central role played by the endothelin superfamily in several pathophysiological conditions, it is important to have a reliable assay for the measurement of these peptides in biological fluids and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Performance of a fully automated fluorometric enzyme immunoassay for serum myoglobin measurement.

An automated fluorometric enzyme immunoassay system for the determination of serum myoglobin has been recently developed. This method is based on the sandwich immunoassay and uses two mouse monoclonal antimyoglobin antibodies; the first one is complexed onto glass fiber paper and the second is conjugated to an enzyme alkaline phosphatase which reacts with the substrate 4-methylumbelliferyl phosphate to generate a fluorescent product. Using a dedicated automated apparatus the time to the first result is eight minutes, with additional values being produced at one-minute intervals (about 50 samples/hour). We compared the analytical performance of this fluorometric enzyme immunoassay with that of a RIA set up in our laboratory for the routine assay of serum myoglobin. The automated fluorometric enzyme immunoassay showed lower between-assay variability (CV = 4.7% vs 13.8%) and higher sensitivity (0.3 ng/mL vs 7.2 ng/mL) than the manual RIA. Moreover, the two immunoassays gave similar results when serum samples of normal subjects and patients with coronary artery disease with or without acute myocardial infarction (AMI) were assayed (fluorometric immunoassay = -0.7 + 0.851 RIA, r = 0.991, n = 137). In conclusion, the automated fluorometric enzyme immunoassay tested in the present study produces reliable clinical results with a rapid turnaround time and therefore can be recommended for use in the early detection of AMI in a laboratory of Coronary Care Unit.

Immunoradiometric assay of serum myosin as a marker of myocardial cell damage: methodological and clinical evaluation.

We evaluated the performance and analytical parameters of a one-step magnetic IRMA kit for the measurement of myosin in serum. The method uses two monoclonal antibodies selected for their high affinity to the heavy chains of human ventricular myosin. The first antibody is coupled to a magnetic solid phase and the second one is labeled with 125I. The working range of the IRMA (range of myosin concentrations measured with an imprecision < 10% CV) was 250-3600 microU/L and the sensitivity 20.8 +/- 7.2 microU/L. The between-assay variability, evaluated from replicate measurements in different runs of two serum pools was 14.6 CV% for the first pool (259.1 +/- 37.8 microU/L) and 14.3 CV% for the second pool (442.0 +/- 63.1 microU/L), respectively. To evaluate the clinical usefulness of myosin as a marker of myocardial cell damage, serum myosin was measured in patients with acute myocardial infarction (AMI) (n = 9) or subarachnoid hemorrhage (n = 20). The results obtained with the myosin assay were compared with those of two other markers considered specific for myocardial necrosis (CK-MB and myoglobin). In eight patients with AMI, serum myosin was elevated 24-36 hours after the onset of chest pain and reached a maximum at 4-7 days, returning to control levels at 8-11 days. The one remaining AMI patient showed two subsequent peaks in serum CK-MB and myoglobin concentrations (thus suggesting an extension of myocardial necrosis), the myosin concentrations reaching their peak only after 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous digitalis-like factors in human milk.

We measured the concentration of endogenous digitalis-like factors (EDLFs) in milk or colostrum of women during nursing on different days after delivery. EDLF concentrations were assayed by a solid-phase RIA involving antidigoxin antibodies and by a radioreceptor assay (RRA) involving human placenta Na+/K(+)-ATPase. The mean (SD) EDLF concentrations as measured by RIA were 35.6 (19.4) ng of digoxin equivalents per liter in milk samples (n = 37) and 61.3 (12.5) ng/L in colostrum samples (n = 5); the mean EDLF concentration as measured by RRA in milk samples (n = 11) was 573 (717) ng/L (range 0-2098). EDLF concentration in milk is greater than circulating concentrations in healthy adults but is comparable with serum concentration in the third trimester of pregnancy. In milk and serum samples (n = 8) collected at the same time, heating and (or) extracting with Sep-Pak C18 cartridges before the RIA produced significantly different EDLF values from those in untreated serum (P less than 0.001) and milk (P = 0.035). EDLF in milk appeared to be not bound or weakly bound to milk protein, as indicated by the fact that boiling did not increase the digoxin-like immunoreactivity.

Endogenous digitalis-like factors (EDLF) in obese individuals: preliminary results.

We measured by RIA the serum and urinary digoxin-like immunoreactivity (EDLF) in 8 subjects with severe obesity and in 10 healthy, non-obese individuals (as a control group), to evidentiate whether circulating and urinary levels of EDLF are increased in obesity. For each individual, we measured the mean EDLF on two sera collected consecutively on two successive mornings, between 8-9 a.m. and the daily urinary EDLF excretion. Every subject collected his/her 24 hour urine in 5 different timed fractions. For each urine fraction, we measured the excretion of EDLF, electrolytes (Na and K), and creatinine. In obese people, the mean serum digoxin-like immunoreactivity (no. 8, 27.3 +/- 8.7 ng/L de) was significantly higher (unpaired t test, p = 0.0002) than in the controls (no. 10, 12.0 +/- 7.3 ng/L de), whereas control and obese subjects had superimposable 24 hour EDLF urinary excretion. Urinary excretion of EDLF significantly changed throughout the day in normals, but not in obese people. In a multiple stepwise regression analysis, urinary K+ and Na+ significantly (p less than 0.01) contributed to the regression with urinary EDLF (EDLF = 76.9 + 0.67 K+ - 0.24 Na+; R = 0.601, no. 40) in obese individuals. The in vivo kinetic and metabolic pathways of EDLF are conceivably different in obese and normal subjects. A difference in the production rate, binding to plasma proteins and/or removal mechanisms could explain the findings of higher circulating levels with normal EDLF urinary excretion in obese persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Does a digoxin-like substance participate in vascular and pressure control during dietary sodium changes in patients with primary aldosteronism?

To evaluate the importance of an endogenous sodium pump inhibitor in the pathogenesis of low renin human hypertension, the urinary excretion of a digoxin-like immunoreactive substance (DLIS) was measured in eight patients with primary aldosteronism (n = 5, with adenomas) during two sequential 1-week periods of low- (20 mmol/l NaCl) and high- (200 mmol/l NaCl) sodium intake. DLIS excretion increased consistently during high-sodium intake while urinary aldosterone, plasma renin activity, cortisol and adrenocorticotropic hormone did not change. Although blood pressure showed a time-course parallel to that of the urinary DLIS, the blood pressure increments were not accompanied by evidence of vasoconstriction since forearm blood flow (plethysmographic technique) increased and forearm vascular resistances were reduced. Moreover, the reactivity of forearm arterioles to local norepinephrine was unchanged during the period of low- and high-salt intake, despite the fact that an endogenous sodium pump inhibitor should, supposedly, sensitize the responses to an adrenergic agonist. Finally, forearm vasoconstrictor responses to ouabain, a pharmacological Na+,K(+)-ATPase antagonist, were potentiated during the high-salt diet, a result not expected if an increased number of sodium pumps were occupied by an endogenous inhibitor. These results provide unequivocal evidence for a modulation by salt intake of the urinary excretion of a DLIS in patients with primary aldosteronism. This substance might participate in the regulation of body fluid volume in this syndrome and possibly in other physiological conditions. However, no evidence could be found for a cause--effect relationship between blood pressure and DLIS increments during high-salt intake, at least during the short-term course of the study.

Atrial natriuretic peptide during different pacing modes in a comparison with hemodynamic changes.

The study investigates the response of atrial natriuretic peptide (ANP) to different cardiac pacing modes in comparison with hemodynamic changes. Ten patients underwent Swan-Ganz catheterization during pacemaker implant. Atrioventricular and ventricular pacing were performed consecutively at three pacing rate levels (80, 100, and 110 ppm). Blood samples were taken from the pulmonary artery for ANP determination, both basally and at the end of each pacing period. Concomitantly, mean pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (PAP) were measured. Cardiac output (CO) was determined by thermodilution both basally and during the 110 ppm steps. During atrioventricular pacing, whereas no significant changes were observed for ANP, PCWP and PAP, CO increased significantly (P less than 0.0005). At the beginning of ventricular pacing hemodynamic parameters and ANP levels were comparable with those of baseline conditions. During subsequent ventricular pacing PCWP and ANP increased significantly at the 110 ppm rate step (P less than 0.05). PAP did not change significantly, whereas CO decreased in all cases (P less than 0.01). A positive correlation was observed between ANP and PCWP during ventricular (P less than 0.001), but not atrioventricular pacing. The results, while confirming the hemodynamic advantages of atrioventricular pacing, point to a major stimulation of ANP secretion during ventricular pacing. This fact, together with the observed drop in CO and the correlation between ANP and PCWP, suggest that the increase of ANP in ventricular pacing may be the expression of a compensatory mechanism to the hemodynamic disadvantages of atrioventricular asynchrony.

Evaluation and comparison of the analytical performances of two RIA kits for the assay of atrial natriuretic peptides (ANP).

We evaluated the analytical performance of two commercial RIA kits for the assay of plasma atrial natriuretic peptide (ANP), which use different antisera and tracers, in order to verify the most suitable RIA procedure for the assay of ANP in plasma samples. In particular, two different procedures for the purification of plasma were evaluated. The first one uses the extraction of plasma samples with Sep-Pack C18 cartridges and the second immunoextraction (C-terminal ANP-specific antibody bound to solid phase of Sepharose). The sensitivity and precision of the two RIA kits proved inadequate, being unable to provide an acceptably precise measurement of the plasma ANP concentrations in normal subjects. An improvement in precision and sensitivity was obtained by using "fresh" (or purified) preparations of the tracer and standard solutions, and by adding PEG to the B/F separation step. The direct assay (without preliminary purification) was not possible due to a serious overestimation of plasma levels due to the presence of interferences; on the other hand, the extraction step increased the imprecision and the complexity of the assay. Moreover, the extraction recovery of ANP added to plasma samples in the procedure using Sep-Pak cartridges is about 50-60%, while it was found to be almost complete (about 90%) in the immunoextraction procedure. Moreover, a comparison of the results obtained with the two RIA systems indicated that the antisera have comparable sensitivities, but quite different specificities; however, neither of the two RIA kits showed a completely satisfactory degree of sensitivity, precision and practicability.

Radioreceptor assay for the measurement of endogenous digitalis-like factors using membrane particulate fraction of human placenta and 125I-digoxin: comparison with RIA method.

We measured purified extracts of serum (plasma) or urine samples of newborns, pregnant women, normal adults, and uremic patients by a radioreceptor assay (RRA), which uses particulate membrane fractions from human placenta as a binding system, and 125I-digoxin as a tracer. We also measured the digoxin-like immunoreactivity by a sensitive RIA, and results were compared with those found by the RRA. Specific 125I-digoxin binding to placental receptors was competitively inhibited by purified plasma and/or urine extracts of newborns, adult subjects, pregnant women and uremic patients. A linear relationship was found between inhibition of binding and volume of plasma and urine assayed. Moreover, a significant correlation was found between the values obtained by RRA and those found by RIA (n = 17, r = 0.699, p = 0.0012). Our data confirm that increased circulating and/or urinary levels of substances with biological and immunological activity similar to cardiac glycoside drugs are present in newborns, pregnant women and uremic patients compared to healthy adult subjects. In addition, our preliminary study indicates that these endogenous factors are able to bind to the specific receptor of digitalis drugs on the placental membranes.

Ultrafiltration: a rational treatment for heart failure.

Patients with late-stage congestive heart failure with significant fluid overload respond well to ultrafiltration. The response is relatively long-standing and includes enhanced responsiveness to diuretics. Ultrafiltration is simple and highly cost effective. Furthermore, it possesses many advantages over massive or drastic pharmacological therapy. In the following paper, we report our own experience and review the world literature.

Increased urinary excretion of digoxin-like immunoreactive substance by insulin-dependent diabetic patients: a linkage with hypertension?

Excretion of digoxin-like immunoreactivity (DLIS) was measured by RIA in timed overnight urine collections from 91 normotensive nondiabetic subjects and 104 normotensive insulin-dependent diabetic (IDDM) patients. The mean +/- SD DLIS excretion rate for the diabetic patients significantly exceeded that for the controls (73 +/- 41 vs 63 +/- 36 pg/min, P = 0.024). In both groups, the mean DLIS excretion rates for men were significantly higher (P = 0.0014, P = 0.006) than for women. In the controls, the DLIS excretion rate significantly correlated with the urinary excretion rate of creatinine (P less than 0.01), Na+ (P less than 0.05), and K+(P less than 0.05), and with the subjects' body weight (P less than 0.01), body mass index (P less than 0.05), and systolic blood pressure (P less than 0.05). In the diabetics, the DLIS excretion rate was significantly correlated with body weight (P less than 0.05) and with urinary excretion rates for albumin (P less than 0.01), creatinine (P less than 0.01), Na+ (P less than 0.05), and K+(P less than 0.05). Our data indicate that: (a) increased amounts of a cardiac glycoside-like substance (or a group of substances) are excreted in the urine of IDDM patients; (b) the urinary excretion of DLIS seems to depend on glomerular filtration rate and physiocochemical properties of glomerular membrane, as well as on subjects' body mass; and (c) because cardiac glycoside-like substances may increase peripheral vascular resistance, increased urinary excretion of DLIS by IDDM patients may indicate a tendency to develop hypertension.