PubMed Health⌕ Search

Biomedical subjects

G Iervasi

Publications and source records attributed to G Iervasi.

At least 19 recordsLinked to original sources
PubMed2006

Serum thyroglobulin measurement: clinical background and main methodological aspects with clinical impact.

It is worldwide recognized that circulating thyroglobulin (Tg) measurement represents a fundamental tool in the follow-up of patients affected by differentiated thyroid cancer (DTC). In the last American and European Consensus Conferences, a surveillance guideline has been extended to the use of thyrotropin (TSH)-stimulated Tg levels for thyroidectomized patients without clinical evidence of residual tumor with Tg below 1 microg/l during TSH suppression. Therefore, sensitivity of the methods is critical to detect small amounts of Tg and/or to observe minimal changes in Tg concentration in the management of DTC patients. It has been proposed that only methods providing the greatest distinction between the lower limit of euthyroid reference range (approximately 3.0 microg/l) and the functional sensitivity limit (at least 1 microg/l) of the assay may offer a suitable clinical sensitivity for detecting small amounts of functioning thyroid tissue in TSH-suppressed state (1 g of normal thyroid tissue results in a serum Tg of approximately 1 microg/l when TSH is normal and about 0.5 microg/l when TSH is suppressed). In the last 30 years sensitivity of Tg measurements has been greatly improved, nowadays methods can achieve very good analytical and functional sensitivity to give reliable results also in the very low concentration range (between 0.1 and 1 microg/l). In addition, with the introduction of fully automated assays, results can be readily available to the clinician while patients are still in the ambulatory area. However, despite the large clinical use of Tg measurement, wide differences (by threefold) still remain between results produced in different laboratories due to poor standardization, heterogeneity of circulating Tg, interference from auto-antibodies, differences in the epitope recognition by antibodies used in the assays.

Biomarkers, Tumor↗
PubMed2006

Thyroid nodule evaluation: what have we really learned from recent clinical guidelines?

Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic algorithm while also reporting important differences. The performance of fine needle aspiration (FNA) for cytological examination follows serum TSH determination and thyroid ultrasonography. Thyroid scintigraphy is recommended following a low TSH value and/or FNA yielding an indeterminate follicular cytology. The use of thyroid ultrasonography is the source of some controversy: though it is recommended as a principal first test, its real-time use to guide FNA ranges from routine to only following an FNA yielding an inadequate or nondiagnostic cytological result. In clinical practice, the proportion of physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently deviates from recommended guidelines. The development of guidelines is necessary to bring about consistency and optimization to the diagnostic work-up of thyroid nodules. It is likely that novel diagnostic procedures, such as molecular markers, large needle aspiration biopsy and thyroid imaging with tracers beyond conventional radioactive iodine or (99m)Tc pertechnetate, will lead to improved performance and implementation of guidelines.

Biopsy, Fine-Needle↗
PubMed2006

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology.

Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the preoperative characterisation of thyroid nodules but this task is difficult for follicular lesions, which often remain undefined. We propose a strategy for improving the preoperative characterisation of selected follicular thyroid proliferations, which is based on large needle aspiration biopsy (LNAB) and galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA-cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell blocks for both cyto/histo-morphological evaluation and galectin-3 expression analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free immunoperoxidase staining method. Preoperative diagnosis was compared to the final histology. LNAB and cell-block technique allow a preliminary distinction between nodules with a homogeneous microfollicular/trabecular structure, as frequently observed in tumours, and lesions with mixed normo-micro-macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14 galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and three adenomas confirmed at the final histology), whereas galectin-3-negative cases were 71 (one carcinoma and 70 benign proliferations at the final histology). Sensitivity, specificity and diagnostic accuracy of this integrated morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%, respectively. In conclusion, LNAB plus galectin-3 expression analysis when applied preoperatively to selected thyroid nodules candidate to surgery can potentially reduce unnecessary thyroid resections.

Adult↗
PubMed2004

Effects of tetraiodothyronine and triiodothyronine on hamster cheek pouch microcirculation.

The aim of the present study was to assess the effects of topically applied triiodothyronine (T(3)) and thyroxine (T(4)) on the arterioles of hamster cheek pouch microcirculation in vivo. Microvessels were visualized using a fluorescent microscopy technique. Topical application of T(3) (3.08, 30.8, 61.5, 307, 615, and 6,150 nM/l) consistently induced dose-dependent dilation of arterioles within 2.0 +/- 0.5 min of administration. The application of T(4) (150, 257, 514, and 5,140 nM/l) caused different dose-dependent effects: dilation at the three lower doses within 16 +/- 2 min and rhythmic diameter changes at the highest dose. Aging of hamsters did not alter the arteriolar responses to T(3) and T(4). T(3)-induced dilation was countered by the inhibition of nitric oxide synthase with N(G)-nitro-L-arginine-methyl ester or N(G)-nitro-L-arginine. Iopanoic acid (IPA), which inhibits types I and II 5'-deiodinase, abolished the dilation elicited by 514 nM T(4) but did not affect T(3)-dependent dilation. 6-Propyl-2-thiouracil (PTU), which inhibits type I 5'-deiodinase only, did not affect the dilation induced by T(4). IPA and PTU did not impair arteriolar dilation induced by acetylcholine or sodium nitroprusside. These results indicate that T(3) induces arteriolar dilation, likely through nitric oxide release. The local conversion of T(4) to T(3) appears to be crucial for the dilation induced by T(4).

Animals↗
PubMed2004

Erythrocyte Na/K-ATPase is increased in subjects with subclinical hypothyroidism.

OBJECTIVE: In erythrocytes of patients with overt hyperthyroidism, the number of ouabain-binding sites and the activity of the Na(+)/K(+)-ATPase have been demonstrated to be decreased, whereas the opposite is true in patients with overt hypothyroidism. No information has been reported on the status of the Na(+)/K(+)-ATPase in subclinically hypothyroid (Sub Hypo) patients. DESIGN: We investigated the number of ouabain-binding sites and Na(+)/K(+)-ATPase activity in erythrocytes of chronic Sub Hypo subjects. PATIENTS AND METHODS: We measured (3)H-ouabain-binding sites in erythrocytes from 15 patients with subclinical hypothyroidism, and compared with those found in 17 normal subjects (N), seven with overt hypothyroidism (Hypo) and 10 with overt hyperthyroidism (Hyper). The activity of the sodium pump was assessed by measuring ouabain-sensitive (86)Rb uptake in a subpopulation of the same groups. RESULTS: The number of ouabain-binding sites in Sub Hypo patients (252 +/- 17; mean +/- SEM) was significantly higher (P < 0.02) than in Hyper (135 +/- 12) and N (203 +/- 10) groups, whereas it was not significant different from Hypo (293 +/- 31). There was a positive correlation between the number of ouabain-binding sites and TSH concentrations (P < 0.002) when Sub Hypo and N groups were considered together. There was a negative correlation between the number of ouabain-binding sites and free thyroxine (FT4; P < 0.0001) and free triiodothyronine (FT3) concentrations (P < 0.001) when all subjects were considered. Ouabain-sensitive (86)Rb uptake (picomoles (86)Rb/h 10(6) cells) in Sub Hypo was significantly higher (4.2 +/- 0.5) when compared with N (2.5 +/- 0.2, P < 0.01) and Hyper (2.5 +/- 0.5, P < 0.02). CONCLUSIONS: Erythrocytes of subclinically hypothyroid patients show a significant increase in the number of ouabain-binding sites and in ouabain-sensitive (86)Rb uptake. The state of erythrocyte Na(+)/K(+)-ATPase may therefore represent a biochemical marker of subclinical hypothyroidism.

Adult↗
PubMed2004

Diagnostic performance of a new highly sensitive thyroglobulin immunoassay.

The determination of serum thyroglobulin (Tg) is commonly used for detecting the presence of residual thyroid tissue or cancer recurrence in patients treated for differentiated thyroid cancer (DTC). The aim of the study was to evaluate the performance characteristics of a recently introduced fully automated chemiluminescent immunoassay, based on four monoclonal antibodies and which produces results in 40 min. Analytical sensitivity (0.01 micro g/l) was computed from 20 replicates of the zero calibrator and of the 'Tg-free' sample pool. Functional sensitivity (0.1 micro g/l at 20 coefficients of variation percent) was determined from the imprecision profile obtained by assaying ten serum pools. The reliability of the measurements in the low concentration range (Tg<1 micro g/l) has been checked by progressive dilution with the 'Tg-free' serum of a sample pool at 5.27 micro g/l; measured values were very close to the expected values (recovery 100-133%).Cut-off at the 99th percentile in DTC stage I 'disease-free' treated patients (n=53) was 0.16 micro g/l. Tg measurement in basal conditions during L-thyroxine suppression therapy and 5 days after recombinant human TSH stimulation was performed in 22 patients with DTC. In 80% of patients with basal Tg<0.1 micro g/l (12/15), Tg remained<0.1 micro g/l after stimulation, and in all of these Tg was<1 micro g/l. Our results have indicated the optimal analytical and clinical performance of this Tg immunoassay and encourage further studies on larger populations of patients with DTC.

Adult↗
PubMed2002

Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study.

The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.

Aged↗
PubMed2001

3,5,3'-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i of human cardiomyocytes in culture.

OBJECTIVE: A decrease in plasma T3 concentration is a frequent finding in patients with heart failure. However, the role of this 'low T3 syndrome' on disease evolution has never been clarified. As phenotypic and functional cardiomyocyte impairments are alterations that correlate with the failing myocardium, we studied the long-term effects of T3 deprivation on human cardiomyocyte structure and calcium handling. METHODS: Atrial cardiomyocytes and myocardial tissue were cultured with or without 3 nM T3. Microscopical examination of structural features was followed by analysis of alpha-sarcomeric actinin and sarcoplasmic reticulum calcium ATP-ase (SERCA-2) content. Calcium handling was studied by [Ca2+](i) imaging. RESULTS: When stimulated with cyclopiazonic acid, a SERCA-2 inhibitor, T3-deprived cardiomyocytes showed significantly faster (P=0.03) and more transient (P=0.04) increases in [Ca(2+)](i) than T3-supplemented cells. Moreover, in the T3-free cultures a significantly lower number of cells (P=0.003) responded to caffeine, a typical activator of sarcoplasmic reticulum Ca(2+)-release channel. T3-deprived cardiomyocytes also presented altered morphology with larger dimensions than T3-supplemented cells (P < 0.0001). Additionally, in T3-deprived samples alpha-sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/- 3% (P < 0.0001) and 74.1 +/- 4% (P=0.005), respectively, when compared with the T3-supplemented group. CONCLUSIONS: Our data show that human cardiomyocyte calcium handling and phenotype are strongly influenced by T3 suggesting important implications of the 'low T3 syndrome' on the progression of heart failure.

Blotting, Western↗
PubMed2001

Hyperthyroidism is associated with lengthening of ventricular repolarization.

OBJECTIVE: Lengthened ventricular repolarization, as assessed by the QT interval on electrocardiogram (ECG), can predispose to an increased risk of cardiac dysrhythmias; no data are available on QT corrected for heart rate (QTc) in hyperthyroidism in vivo. DESIGN: QT and RR intervals from 24 h ambulatory ECG Holter recording were measured in patients with hyperthyroidism and again following pharmacological achievement of stable euthyroidism for at least 2 months. PATIENTS: We enrolled a total of 16 hyperthyroid patients with Graves' disease, six males and 10 females (mean age 47 +/- 4 years, mean +/- SEM); 13 healthy age- and sex-matched subjects were utilized as a control group. MEASUREMENTS: The QT analysis was carried out by a computerized algorithm (QTc was corrected by the heart rate by Bazett's formula). Serum total T4, total T3, free T4, free T3 and TSH concentrations were measured by a fully automated immunoenzymometric assay; plasma norepinephrine by automatized high-pressure liquid chromatography, potassium and chloride by a potentiometric method, magnesium and calcium by a colourimetric method. RESULTS: The 24-h average QTc in the hyperthyroid patients was significantly prolonged compared to controls (458 +/- 7 vs. 431 +/- 6 ms, P = 0.01) and it returned to normal after treatment of thyrotoxicosis (432 +/- 6 ms, P < 0.05 vs. time H, NS vs. controls). QTc positively correlated with FT3 (r = 0.63, P < 0.001) and with FT4 (r = 0.481, P < 0.02). Conversely, QTc did not correlate with plasma basal norepinephrine levels, nor with electrolytes. CONCLUSIONS: Hyperthyroidism is associated with prolonged QTc that normalizes once the patient becomes euthyroid. The strong positive correlation between FT3 and QTc supports the hypothesis of an important role of thyroid hormone on modulation of QTc lengthening.

Adrenergic beta-Antagonists↗
PubMed2001

A radioimmunoassay for type I iodothyronine 5'-monodeiodinase in human tissues.

We have developed a sensitive, specific and reproducible radioimmunoassay (RIA) for measurement of human type I monodeiodinase (5'-DI) protein. Anti-5'-DI antibody was produced by immunization of rabbits with a conjugate of bovine serum albumin and a 16 amino acid synthetic peptide, corresponding to a portion of the carboxy-terminal region of the human 5'-DI (PI-99). In a final dilution of 1:500, our anti-5'-DI antibody bound about 30%-35% of a tracer amount of 125I-PI-99. The detection threshold of the RIA approximated 0.4 pmol PI-99 or an equivalent amount of 0.4 pmol 5'-DI. The coefficient of variation averaged 5% within an assay and 14% between assays. Dose-response curves of tissue proteins were essentially parallel to that of PI-99. In a total number of 35 normal human tissue samples, the mean (+/- standard deviation [SD], picomole per milligram of protein [pmol]) 5'-DI content was 25 +/- 6.7 in kidney, it was significantly lower (p < 0.05) in liver at 3.9 +/- 1.1, 2.8 +/- 0.8 in intestine, 2.3 +/- 0.98 in adrenal, 4.2 +/- 2.5 in skeletal muscle, 3.8 +/- 1.4 in heart and 2.6 +/- 2.4 in thyroid; it was 1.4 +/- 0.3 in Graves' thyroid. Our data suggest that (1) 5'-DI is distributed widely among human tissues; (2) kidney is the tissue most enriched with 5'-DI; (3) 5'-DI content in the thyroid is not increased in Graves' disease.

Adult↗
PubMed2000

A study of iodothyronine 5'-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues.

The present study was undertaken to investigate the peripheral iodothyronine 5'-monodeiodination in different human and rat tissues. We studied iodothyronine 5'-monodeiodinase type I (5'-DI) activity in liver, kidney, intestine, right cardiac atrium and skeletal muscle and we compared the results with those in rat tissues. Lodothyronine 5'- monodeiodinase type II (5'-DII) activity was studied in normal and ischemic human heart and in rat normal myocardium and brain. The 5'-DI activity (fmol/min x mg protein) in liver and kidney was significantly higher (p < 0.001, ANOVA) in normal rat tissue than in human. However, no significant differences were observed in 5'-DI activity between normal and tumoral human intestine or between intestinal tissue of man and rat. 5'-DI activity in normal human skeletal muscle was significantly higher than that in rat skeletal muscle (p < 0.05). The 5'-DI activity was lower in human ischemic myocardium when compared to normal myocardium either in humans (p < 0.05) or rat (p < 0.001). The Km of 5'-DI was significantly lower in rat than in human kidney and liver (p < 0.05). We conclude that 1) 5'-DI is distributed widely among extrathyroidal human and rat tissues and 5'-DII activity is detectable both in human and rat heart; 2) 5'-DI activity in liver and kidney is lower in man than in rat; 3) 5'-DI activity in the skeletal muscle is higher in man than in the rat; 4) 5'-DI activity is decreased in tumoral tissues of human liver and kidney and in ischemic myocardium, while no significant difference was found between human and rat cardiac 5'-DII activity.

Aged↗
PubMed2000

Turnover studies on cardiac natriuretic peptides: methodological, pathophysiological and therapeutical considerations.

Cardiac natriuretic peptide hormones (ANP and BNP) are synthesized and secreted by the heart, producing several biological effects, such as natriuresis, vasorelaxation, hypotension, and neuromodulation. Extensive studies conducted in both animals and humans have documented that cardiac natriuretic peptides (CNPs) are secreted into the circulatory system via the coronary sinus into the right atrium, and then rapidly degraded and removed from the blood by plasma proteases and specific clearance receptors. Usually, studies of CNPs kinetics have been carried out following an experimental protocol in which labeled or unlabeled hormone is administered (by constant infusion or bolus injection) and the corresponding concentration of the hormone is measured in peripheral venous blood. However, when a uniform intravascular concentration throughout artero-venous vessels is lacking due to the very rapid clearance of the substance being studied (such as CNPs), the classical compartmental or none compartmental approach may not be suitable for interpreting the experimental data. In this case, a more physiological circulatory model, which does not assume a uniform intravascular distribution of the hormone and comprises several anatomo-functional blocks arranged in a series and supplied by the same flow (cardiac output) should be adopted. Different experimental designs (infusion or bolus injection) as well as multiple sampling sites (aorta and pulmonary artery, inferior vena cava, femoral vein) were used in ANP kinetic studies. Using a circulatory approach, ANP has been demonstrated to be rapidly distributed and degraded; in healthy subjects about 50% of ANP secreted into the right atrium is extracted by the peripheral tissues during the first pass throughout the body. Since CNPs have important fluid-volume regulatory features, it has been postulated that they also play a key role in volume homeostasis in several pathophysiological states, such as congestive heart failure. Indeed, a markedly altered degradation and distribution of ANP in patients with cardiac failure who show a resistance to its natriuretic effects, even in those on the early stage of clinical disease, whose CNPs plasma levels are in the normal range, have been demonstrated. Recent studies indicate that some drugs, by inhibiting the degradation of CNPs by plasma proteases and can thus affect CNP kinetics, may be useful in the treatment of arterial hypertension and cardiac failure.

Animals↗
PubMed1999

Circulating levels of cardiac natriuretic hormones measured in women during menstrual cycle.

Alterations in fluid and electrolyte balance represent a common complaint by women during different stages of the menstrual cycle; however, conflicting results concerning the possible role of plasma Atrial Natriuretic Peptide (ANP) modifications during the menstrual cycle have been reported. This may be due to differences in assay methods or in the clinical protocol adopted. Moreover, possible variations in plasma Brain Natriuretic Peptide (BNP) levels during the menstrual cycle have not been studied. We measured the plasma levels of ANP and BNP by means of two highly sensitive and specific immunoradiometric assay (IRMA) methods in 19 normal women without premenstrual symptoms, in order to evaluate whether significant modifications of these hormones are present during the menstrual cycle. Because it is well-known that circulating levels of cardiac hormones show great variations in normal subjects due to their rapid plasma half lives, blood samples were collected at 2.5-min intervals over a 15-min period on the 5th and 24th days of the cycle. The mean (+/-SD) values of ANP (follicular phase=15.1+/-8.7 pg/ml; luteal phase=14.8+/-9.5 pg/ml) and of BNP (follicular phase=13.0+/-15.0 pg/ml; luteal phase=11.2+/-11.4 pg/ml) did not show significant variations during the menstrual cycle. Moreover, the variability of ANP values (CV=24.8+/-13.2%) was significantly higher (p=0.0318) than that of BNP values (CV=16.5+/-8.9%), and a significant correlation was found between the mean ANP and BNP values of the individual women studied (R=0.407, p=0.0437). The values of estradiol, progesterone, LH, FSH and prolactin did not correlate with the ANP or BNP values. In conclusion, our results indicate that circulating levels of cardiac hormones do not show any significant modifications during the menstrual cycle in healthy women.

Adolescent↗
PubMed1999

Pathophysiologic relevance of measuring the plasma levels of cardiac natriuretic peptide hormones in humans.

Cardiac natriuretic peptides (ANP, BNP, and biologically active peptides of the N-terminal proANP1-98) are differently regulated in their production/secretion patterns and clearance rates; consequently, the assay for these peptides may provide complementary (or even different) pathophysiological and/or clinical information. The assay for cardiac natriuretic peptides has been utilized in clinical conditions associated with expanded fluid volume. In particular, this assay can be useful in discriminating between normal subjects and patients in different stages of heart failure and can also be considered a prognostic indicator of long-term survival in patients with heart failure and/or after acute myocardial infarction. Non-competitive immunometric assays (such as two-site IRMAs), even if more expensive, seem to be preferable to RIAs for routinary assay of cardiac peptide hormones because they generally have a better degree of sensitivity, accuracy, and precision.

Amino Acid Sequence↗
PubMed1998

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.

Adult↗
PubMed1998

Circulatory model in metabolic studies of rapidly renewed hormones: application to ANP kinetics.

In an attempt to identify and quantify the sites of atrial natriuretic peptide (ANP) degradation, a new tracer experiment has been developed. 125I-ANP was injected as a bolus just upstream from the right atrium, and blood was sampled from two different sites (pulmonary artery and aorta) in eight cardiac patients. Data were analyzed using a physiologically based circulatory model consisting of three blocks in series (right heart, lungs and left heart, and periphery) supplied by the same flow (cardiac output, measured by thermodilution); the extraction coefficients of the three blocks and of the whole body could be determined from the areas under tracer concentration curves in plasma (AUCs). The values for AUCs (means +/- SD) were 64.8 +/- 9.4 and 65.5 +/- 10.7% dose.l-1.min-1 for pulmonary artery and aorta curves, respectively; the area under the pulmonary artery curve could be subdivided into the area under the first-pass curve (30.6 +/- 4.7% dose. l-1.min-1) and the area under the recirculating curve (34.0 +/- 7.7% dose.l-1.min-1). The metabolic clearance rate of 125I-ANP, computed as dose divided by the area under the recirculating curve, was 3.1 +/- 0.7 l/min, and the whole body extraction was 47.6 +/- 6.6%. In our patients with myocardial dysfunction, neither right heart block nor lungs and left heart block significantly extracted ANP, and periphery block accounted for almost all removal of the hormone from the blood.

Adult↗
PubMed1998

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.

Adult↗