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Biomedical subjects

A Clerico

Publications and source records attributed to A Clerico.

At least 37 records · Page 2Linked to original sources
PubMed1999

A rapid procedure for the quantitation of natriuretic peptide RNAs by competitive RT-PCR in congenital heart defects.

We report an original application of quantitative reverse transcription-polymerase chain reaction (Q.RT-PCR) for the evaluation of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP) and beta-actin mRNA in small atrial samples (10-15 mg). A fixed amount of total RNA was simultaneously reverse transcribed and amplified with dilutions of a competitor RNA fragment used as a control. We constructed a single synthetic RNA competitor for ANF, BNP and beta-actin. The competitors and targets shared the same primer sequences but yielded PCR products of different sizes. We have investigated ANF, BNP and beta-actin gene expression in patients affected by congenital heart defects (CHD) during the surgical correction of the defect. We collected a right atrial sample from each patient before the start of cardiopulmonary bypass. We studied 14 patients affected by tetralogy of fallot (no. 6), complex CHD (no. 4), and ventricular septal defect (no. 4). The results indicate that the Q.RT-PCR represents a simple, highly specific, non radioactive procedure for the quantification of natriuretic peptide gene expression and is particularly suitable for evaluation of gene expression in small myocardial samples. Our data also suggest that: 1) there is a significant relationship between the levels of ANF, BNP and beta-actin mRNA and the type of CHD; 2) the levels of BNP mRNA are more variable than ANF; 3) the beta-actin seems to be unsuitable for normalising cardiac gene expression in CHD because mRNA basal levels of this protein vary greatly among patients with different type of CHD.

Actins↗
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↗
PubMed1999

[Physiological significance and clinical utility of analytical methods for cardiac natriuretic peptides].

It was well-established that the heart has an endocrine function because it is able to synthesize and secrete a family of related peptide hormones (known as cardiac peptide hormones) with potent diuretic, natriuretic and with complex interactions with the hormonal and nervous systems. 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 as 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. The technical characteristics and the potential clinical usefulness of some of the methods for measuring these peptides are reviewed.

Animals↗
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

Effects on platelet function of combination etoposide and carboplatin chemotherapy in pediatric oncology patients.

The effects of a therapeutic course of the combination of carboplatin and etoposide on platelet function have been evaluated in 10 pediatric patients with brain tumors. Platelet count, in vitro aggregation tests, P-selectin expression and agonist-induced ATP release were evaluated before, and 7 and 15 days after one cycle of chemotherapy. The analysis of the results demonstrated the presence of an in vitro platelet aggregation defect in response to collagen and arachidonic acid in all patients 7 days after therapy. A concomitant decrease of collagen- and arachidonic acid-induced ATP release was also observed. Both platelet aggregation and ATP release returned to baseline values 15 days after chemotherapy administration. Conversely, in vitro platelet aggregation and secretion induced by ADP and epinephrine were unaltered by carboplatin and etoposide administration. Furthermore, P-selectin expression was negative at baseline and did not change after chemotherapy. These results support the hypothesis that combination etoposide and carboplatin chemotherapy in pediatric patients is responsible for possible disturbances in biochemical pathways required for platelet secretion and aggregation.

Journal Article↗
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↗
PubMed1998

Applicability of a circulatory model for determining the parameters of kinetics of endogenously produced compounds.

The applicability of circulatory model approach for determining the kinetic parameters of endogenously produced substances has been demonstrated based on the assumption that the behaviour of newly produced molecules of a compound inside its production spaces is the same as that of the molecules returned due to recirculation of blood. While extraction and transmission parameters can be estimated by using tracer data, total mass cannot be determined without additional information. This information could be obtained from data of some suitable metabolite by using double tracer method. Circulatory model is especially suitable for studies of substances with a fast kinetics and renewal if blood (plasma) flow is measured independently.

Blood Circulation↗
PubMed1998

Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p < 0.001) in the heart rate values in comparison with diabetic patients, in whom a significant decrease (p < 0.001) was found only at the 4th day. A significant (p = 0.0004), more rapid onset of the antiarrhythmic response to the drug was found in nondiabetic patients (6.8 +/- 6.0 h) in comparison with diabetic patients (98.0 +/- 14.8 h). Our findings suggest that the antiarrhythmic effects of amiodarone in diabetic patients with uncontrolled atrial fibrilation or atrial flutter may be delayed in comparison with nondiabetic patients. This altered response may be (at least in part) due to the diabetic autonomic neuropathy. Our study indicates that the presence of diabetes mellitus always must be taken into account when patients are enrolled for large, prospective, randomized trials, planned to evaluate the antiarrhythmic effects of amiodarone given intravenously.

Adult↗
PubMed1997

Successful management with interferon alpha-2a after prednisone therapy failure in an infant with a giant cavernous hemangioma.

A giant cavernous hemangioma of the left arm with severe thrombocytopenia and consumptive coagulopathy was observed in a neonate. Initial treatment with prednisone, platelet transfusions, and clotting replacement failed to control the bleedings. The child was then treated with daily subcutaneous infusions of interferon alpha-2a. Coagulopathy rapidly improved and transfusions were drastically reduced. The hemangioma regressed progressively and disappeared after 4 months of treatment.

Adult↗
PubMed1997

Ganciclovir therapy for cytomegalovirus-associated liver disease in immunocompetent or immunocompromised children.

Ganciclovir therapy was given intravenously to 20 children with cytomegalovirus (CMV)-associated liver disease, of whom 6 were immunocompetent and 14 were immunocompromised (9 had AIDS and 5 had solid tumors). Immunocompetent children had isolated liver disease diagnosed at birth (4 children), or systemic congenital CMV infection including liver disease (2 children). Ganciclovir was used following two regimens: A) 5 mg/kg twice daily for 8 to 86 days (mean 21); B) 7.5 mg/kg twice daily for 14 days followed by 10 mg/kg three times weekly for three months. CMV infection was diagnosed by viral isolation, detection of viral antigens, and/or CMV DNA from blood and urine. All immunocompetent children had negative CMV culture and CMV DNA detection from blood and/or urine after 14 weeks of treatment. However, the three children who were treated with regimen B showed normal ALT levels at the end of the maintenance course, whereas the children who received ganciclovir with regimen A had normal ALT levels only after about 1 year. All children with tumors initiated regimen B, but only three, who had negative CMV detection and markedly decreased ALT levels, received full treatment; of the remaining two children, one recovered after only an initial course, and the other had therapy interrupted because of hepatic failure and died 9 days later. In contrast, the children with AIDS received several ganciclovir courses for different periods at the lower dosage: they generally improved during treatment but did not recover completely, and five children died with active CMV infections. Based on our study, CMV-associated liver disease can be efficiently treated with ganciclovir both in immunocompetent and immunodeficient children. However, a single ganciclovir course including a higher dosage and prolonged therapy appeared to be more effective than several courses with lower dosages.

AIDS-Related Opportunistic Infections↗
PubMed1997

Acute effects of intravenous amiodarone on sulphate metabolites of thyroid hormones in arrhythmic patients.

OBJECTIVES: Factors that contribute to the remarkably rapid decrease in serum T3 and increase in reverse T3 (rT3) levels during illness, fasting, or treatment with some drugs (e.g. amiodarone) are not clear. In order to understand better the effect of acute amiodarone administration on T3 metabolism, especially the sulphation pathway, we performed a prospective study in 8 arrhythmic in-patients treated with a loading dose of amiodarone. DESIGN: Amiodarone was administered by i.v. infusion of 20 mg/kg/day on day 1 and 10 mg/kg/day on day 2, followed by 600 mg/day orally throughout the study. Two serum samples for amiodarone and hormone assays (thyroid hormones, TSH, and the sulphate metabolites of 3'-T1, 3,3'-T2, and T3) were collected before the start of therapy, every 12 h during the first 3 days of amiodarone administration, and then once a day for 2-10 days. SUBJECTS: Eight patients (4 men and 4 women, aged 44-82 years), who were treated with amiodarone because of cardiac dysrhythmia, were enrolled in the study. RESULTS: Serum concentrations of total T4 significantly increased in the last 3 days of the study (ANOVA, P = 0.0002). However, serum total T3 progressively and significantly decreased throughout the study (ANOVA, P < 0.0001). Serum free thyroid hormone concentrations (free T3 and free T4) did not significantly change during the study. Serum rT3 (ANOVA, P < 0.0001) and TSH (ANOVA, P = 0.0009) rapidly and progressively increased throughout the study. Starting from the first 24 h, serum concentrations of T3 sulphate (T3-S) significantly and progressively increased from (mean +/- SD) 0.057 +/- 0.029 nmol/l under basal conditions to 0.089 +/- 0.036 nmol/l after 5 days of amiodarone therapy (ANOVA, P = 0.0011). Since total T3 levels progressively decreased throughout the study, the ratio of the T3-S and total T3 values progressively increased from 4.8 +/- 2.7% under basal conditions to 10.6 +/- 7.3% after 5 days of amiodarone therapy (ANOVA, repeated measures, P < 0.0001). Basal serum concentrations of sulphate metabolites of T2 (T2-S, 2.22 +/- 1.7 nmol/l) and T1 (T1-S, 1.29 +/- 0.74 nmol/l) did not significantly change throughout the study. CONCLUSIONS: Our data indicate that a loading dose of intravenous amiodarone in patients with cardiac dysrhythmias is followed by a very rapid and progressive increase in circulating T3-S levels, possibly due to an inhibition of type 1-iodothyronine de-iodinase. Since T2-S and T1-S, common final metabolites of the thyroid hormone sulphation pathways remained unchanged, our data suggest that the total amount of thyroid hormone degraded by sulphation pathways remains unaltered during amiodarone treatment. Finally our findings are compatible with the view that sulphation represents an important pathway for T3 metabolism in vivo in man.

Administration, Oral↗
PubMed1997

Ceftriaxone as a single agent in empirical therapy of unexplained fever in granulocytopenic children with solid tumors.

The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis.

Adolescent↗
PubMed1997

Acute effects of amiodarone administration on thyroid function in patients with cardiac arrhythmia.

Because little has been published on early effects of treatment with amiodarone on thyroid function, we studied serum total and free thyroid hormone, reverse T3, and TSH levels in patients with cardiac arrhythmias during the first 10 days of treatment with a loading dose of amiodarone by iv infusion. Twenty-four patients were enrolled in the study. A standardized loading regimen for the i.v. infusion of amiodarone was used. The protocol provided the i.v. infusion of 20 mg/kg per day on day 1, the i.v. infusion of 10 mg/kg per day on day 2, then 600 mg/day per os for 7-10 days, and finally, in patients chronically treated with the drug, the dose was gradually reduced to 400-200 mg/day per os. Total and free concentrations of T4 tended to progressively and significantly increase (P < 0.0001 repeated measures ANOVA) starting from the fourth day of therapy, whereas total T3 decreased from the second day progressively (P < 0.0001) throughout the study; free T3 did not significantly change. TSH levels early and significantly (P < 0.001, by ANOVA) increased throughout the study, starting from the first day of therapy and reaching at 10 days a value 2.7 times higher than the basal value. Reverse T3 levels progressively and significantly (after 2 days of treatment) increased and paralleled the TSH values, reaching at the 10th day a value about 2 times higher than basal value. In conclusion, our data suggest that after i.v. treatment with amiodarone: 1) TSH is the first hormone to change significantly followed by reverse T3, T4, and T3; 2) the progressive fall of T3 levels reflects an inhibition of the peripheral conversion of T4 to T3; 3) the observed later increase of total and free T4 levels may be explained by a contribution of direct thyroidal stimulation by TSH and/or by a reduction in T4 clearance.

Aged↗
PubMed1997

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.

Adult↗
PubMed1996

Acute enoximone effect on systemic and renal hemodynamics in patients with heart failure.

Patients with heart failure generally show improvement in their clinical condition after enoximone infusion over the period of treatment; this effect cannot be ascribed only to the known hemodynamic action of this drug. Thirty-six patients (age range 44-82 years) with heart failure (NYHA class II-IV) underwent 48-hour enoximone infusion to study whether this prolonged improvement might depend on changes in systemic or renal hemodynamics or in neurohormonal balance. All patients underwent Swan-Ganz hemodynamic monitoring; renal plasma flow, glomerular filtration rate, plasma atrial natriuretic factor (ANF), and plasma renin activity (PRA) were all measured at baseline, at the peak of the enoximone action, and 48 hours after drug discontinuation. The main hemodynamic parameters were significantly improved during enoximone infusion and after drug discontinuation. The cardiac index basal value of 2.2 +/- 0.1 l/min/m2 increased to 3.1 +/- 0.1 l/min/m2 after 24-hour therapy (p < 0.01); similarly, pulmonary wedge pressure, mean pulmonary arterial pressure, and right atrial pressure decreased markedly (p < 0.01). Beneficial effects were also observed in renal hemodynamics; indeed, renal plasma flow (basal value 485 +/- 39 ml/min) increased significantly after 24-hour enoximone infusion (575 +/- 35 ml/min; p < 0.01), and this tendency was also observed 48 hours after drug discontinuation. No significant modifications were observed in plasma hormone data; however, the PRA plasma level had a tendency to decrease. We conclude that in patients with heart failure, enoximone infusion has a less marked effect on renal hemodynamics, but this is more lasting than systemic hemodynamic effects. The tendency of PRA to decrease (although not statistically significant), still detectable 2 days after treatment in the presence of steady high plasma ANF concentrations, may also contribute to the paradoxical longlasting benefit despite the short-lived improvement in systemic hemodynamics after brief cycles of enoximone infusion.

Adult↗