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Biomedical subjects

A Biagini

Publications and source records attributed to A Biagini.

At least 55 records · Page 3Linked to original sources

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).

Adult↗

Altered tissue degradation and distribution of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy and its relationship with clinical severity of the disease and sodium handling.

BACKGROUND: Atrial natriuretic peptide (ANP) has been suggested to play an important role in heart failure, preserving cardiorenal homeostasis through maintenance of the sodium balance and inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether there is a disturbed renewal and distribution of ANP in patients with idiopathic dilated cardiomyopathy (IDC) with differing clinical severity of disease. METHODS AND RESULTS: We used a tracer method to perform a cross-sectional study of 15 IDC patients with differing clinical severity (New York Heart Association functional class I to III), prospectively divided into two groups according to their functional class (group 1, classes I and II; group 2, classes II-III and III). Eleven normotensive, nonobese male volunteers also were studied as a control group. Main ANP kinetic parameters were derived from the disappearance curve of the labeled hormone after the bolus injection of [125I]-labeled ANP. A high-performance liquid chromatography technique was used to separate the radiolabeled hormone in each plasma sample. Patients in group 1 showed higher ANP metabolic clearance rate (MCR) (2731.9 +/- 726.2 mL.min-1.m-2) than patients of group 2 (1718.4 +/- 621.2 mL.min-1.m-2) and control subjects (1873.1 +/- 551.2 mL.min-1.m-2). ANP disposal (MCR) positively correlated with biological hormonal effect (urinary sodium excretion) both in control subjects and in patients. In IDC patients of both groups, however, MCR values were always higher (approximately doubled) than the values found in control subjects at the corresponding sodium excretion. This finding indicates that a reduced ANP biological activity is associated with hormone degradation in patients. Moreover, patients of group 2 showed significantly higher ANP production rates (395.6 +/- 183.8 ng.min-1.m-2) than group 1 (166.0 +/- 139.0 ng.min-1.m-2) and control subjects (130.7 +/- 105.4 ng.min-1.m-2) despite a marked reduction in sodium excretion. Patients with IDC showed a progressive reduction in the total distribution volume (group 1, 19.8 +/- 5.8 L/m2; group 2, 12.7 +/- 6.9 L/m2; control subjects, 27.0 +/- 11.6 L/m2) of the hormone; this probably was due to a reduction in exchanges of ANP with peripheral tissues. CONCLUSIONS: Our study demonstrates a markedly altered degradation and distribution of ANP in patients with IDC, even in those at the early stage of clinical disease (classes I and II, group 1) who have ANP plasma levels in the normal range.

Adult↗

Thyroid hormones homeostasis in pediatric patients during and after cardiopulmonary bypass.

The concentrations of thyroid hormones were measured in 14 pediatric patients before, during, and after cardiopulmonary bypass. The ages of the patients ranged between 18 months and 14 years. Patients were kept normothermic, or moderate or deep hypothermia was induced depending on the specific pathologic condition involved. A marked reduction in the levels of total triiodothyronine, total thyroxine, free triiodothyronine, and thyroid-stimulating hormone, and in the ratio of free triiodothyronine to free thyroxine was detected during the time frame of the study. The minimum levels of each hormone were reached between 12 and 48 hours after cardiopulmonary bypass, indicating that changes in thyroid function and in the conversion of thyroxine to triiodothyronine are triggered by cardiopulmonary bypass and represent specific phenomena, and that these changes are progressively exacerbated during the post-operative period. The thyroid-stimulating hormone level was markedly reduced versus its baseline values (24% +/- 0.13%), despite low levels of both total (40% +/- 18%) and free (39% +/- 20%) triiodothyronine: it returned to its preoperative level by the third postoperative day, but both the total (75% +/- 10%) and free (74% +/- 3%) triiodothyronine levels remained below their baseline values for 7 days postoperatively. Neither hemodilution nor hypothermia was responsible for the alteration observed. We conclude that pediatric patients undergoing cardiopulmonary bypass manifest changes in hormone metabolism similar to those seen in adult patients. These changes increase progressively during the postoperative period, and are still present 7 days postoperatively. The exact mechanism responsible for causing these changes is not thoroughly understood. Whether triiodothyronine replacement therapy is beneficial or deleterious remains controversial.

Adolescent↗

Measurement of serum amiodarone and desethylamiodarone by HPLC: its usefulness in the follow-up of arrhythmic patients treated with amiodarone.

Amiodarone is an antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias. Owing to its narrow therapeutical range, monitoring of drug concentration is mandatory. The circulating and tissue levels of amiodarone and of its main endogenous metabolite, N-desethyl-amiodarone, are currently measured by means of HPLC procedures, which are tedious and time-consuming, and often beset with problems and drawbacks. We have developed a new chromatographic assay for the simultaneous measurement of amiodarone and N-desethyl-amiodarone in serum samples, and tested its usefulness in the follow-up of 14 patients (8 men and 6 women, age range 40-65 years) with complex ventricular arrhythmias, treated with amiodarone for at least 5 weeks. This assay uses trifluoperazine dihydrochloride as internal standard and a preliminary extraction of serum samples with isopropyl ether. The assay procedure was the following: 350 microliter patient's serum, to which 1 microgram trifluoperazine was added, were extracted with 280 microliter isopropyl ether. After mixing and centrifugation, 50 microliter of the organic layer were filtered and then injected onto the HPLC system (15 cm x 3.9 mm Resolve 5-micrometer spherical silica column); the elution rate was 1.8 ml/min (mobile phase, 920 ml of methanol and 80 ml of ammonium sulfate buffer) in isocratic condition. The time for a complete assay of each serum sample was less than 20 min, and its working range was 0.1-5.0 microgram/ml of amiodarone. An excellent recovery of the drug from subtherapeutical values up to toxic amiodarone concentration was obtained. The intra-assay precision of amiodarone assay ranged form 5 to 11%, while the between-assay precision administered in all patients, without increasing the amiodarone concentration beyond the toxic threshold level. The plateau of the circulating levels of the drug was generally reached in about 5-12 days, at the acceptable therapeutical range, from 0.5 to 2 microgram/ml. In conclusion, this chromatographic method for the assay of serum amiodarone levels is sufficiently simple, rapid and reliable to be considered a useful tool in the follow-up of arrhythmic patients chronically treated with amiodarone.

Adult↗

Determination of endothelin binding sites in bovine atrium and ventricle membranes: a model for binding studies in human cardiac tissue.

The characterization of the binding sites of endothelin (ET) could constitute a useful tool to better understand its role in different pathophysiological conditions in human myocardial tissue. Crude membrane fractions were prepared from bovine atrium and ventricle for binding-assay assessment; membranes were also prepared from portions of atrium or ventricle < 100 mg each, a size comparable with human surgical fragments, and Scatchard analysis was performed from each single fragment. Portions of cardiac tissue were homogenized in 10 volumes of Tris/HCl buffer, 50 mM, pH 7.4, containing protease inhibitors; the supernatant was centrifuged at 50,000 x g for 30 min and the pellet stored at -80 degrees C. 125-I-ET-1 binding was performed by using 50 micrograms of protein and scalar concentrations of radioligand (8-200 pM), at 37 degrees C for 4 h and was stopped by filtration through a glass-fibre filter. The specific binding was saturable (at 200 pM of 125-I-ET-1 for 100 micrograms/ml of protein); the equilibrium was reached in 4 h at 37 degrees C at a radioligand concentration of 150 pM; a similar pattern, but a lower binding was obtained at 4 degrees C and 25 degrees C; the binding linearly increased with protein concentrations from 12.5 to 150 micrograms, and saturated at higher concentration. Non-specific binding was determined in presence of 0.1 microM unlabelled ET-1 and was about 2% of the total radioactivity added, for 125-I-ET-1 ranging from 8 to 200 pM, at 100 micrograms/ml of protein. By Scatchard analysis Kd proved to be 20.7 +/- 3.9 and 19.9 +/- 0.6 pM, Bmax 42.4 +/- 12.7 and 59.3 +/- 13.0 fmol/mg of protein, for atrium and ventricle respectively. Differential inhibition of binding was observed for the three ET isoforms; IC50 were similar for atrium and ventricle and proved to be 50 nM for ET-1 and ET-2 and > 200 nM for ET-3. This latter finding and the Scatchard analysis suggest the presence of a single class of binding sites in bovine cardiac membranes. No significant differences in absolute values of Kd and Bmax were found when cardiac membranes were obtained by small tissue fragments.

Animals↗

Kinetic study of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy: evidence for resistance to biologic effects of the hormone even in patients with mild myocardial involvement.

Atrial natriuretic peptide (ANP) kinetics was studied in 12 patients with idiopathic dilated cardiomyopathy at different sodium excretion (30-175 mmol/day) and variable degrees of hemodynamic dysfunction [New York Heart Association (NYHA) class range I-III] to investigate whether differences in renewal and distribution of this hormone (as compared with those of a control group) play a role in pathogenesis and evolution of heart failure. [125I]Labeled ANP was injected as a bolus, and a high-performance liquid chromatography (HPLC) procedure was used to purify the labeled hormone in venous plasma samples collected for < or = 50 min after injection; the main ANP kinetic parameters were then derived from the disappearance curve of the labeled hormone. As in controls, a positive linear regression between ANP metabolic clearance rate (MCR, ml/min/m2) values and daily urinary excretion of sodium (NaUE, mmol/day) was noted in patients. The different linear regression coefficients between normal subjects (MCR = 365 +/- 8.08 NaUE, r = 0.986, p < 0.0001) and patients (MCR = 497 + 18.5 NaUE, r = 0.867, p = 0.001) indicate that in patients a higher peptide clearance rate is needed to obtain the same biologic effect (sodium excretion) and suggest that resistance to biologic effects of the hormone exists in patients at an early stage of disease (NYHA class I). When the efficiency of the ANP system in excreting sodium was expressed as the ratio of NaUE to ANP production rate (PR = MCR x ANP plasma concentration, microgram/day/m2) patients showed significantly lower values (p = 0.0126) than normal volunteers, thus confirming resistance to the hormone effects. Significantly lower values for ANP total distribution volume (16.5 +/- 8.4 L/m2), mean residence time in the sampling space (4.04 +/- 1.14 min), mean residence time in the body (7.25 +/- 2.13 min), and fewer recycles through the initial (sampling) space (0.27 +/- 0.16) were noted in patients, indicating an altered mechanism regulating distribution of the hormone. The positive correlations between ANP MCR (L/min/m2) values and cardiac index (CI, L/min/m2) (MCR = -1.24 + 1.17 CI, r = 0.689, p = 0.0092) and between initial distribution volume (IDV, L/m2) and CI (IDV = -11.2 + 6.85 CI, r = 0.730, p = 0.0046) in all patients indicate that hemodynamic factors contribute to the progressive reduction in MCR and IDV values throughout the progression of myocardial involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Prognostic value of the dipyridamole echocardiography test performed early after aortocoronary bypass surgery.

It has been demonstrated that high dose (up to 0.84 mg/kg over 10 min) dipyridamole echocardiography stress testing is feasible even in the first few hours after coronary artery bypass graft surgery and can be used to assess the beneficial physiological effects of coronary revascularization as well as graft patency. The aim of this study was to assess the role of dipyridamole echocardiography testing performed shortly after myocardial revascularization in the stratification of prognosis during follow-up. We studied 49 consecutive patients (45 males and 4 females; mean age 56 +/- 8 years) referred to our institute for elective myocardial revascularization. Six patients had single, 14 double, and 29 triple vessel disease. Forty-two left internal mammary artery grafts, 16 sequential venous grafts, and 45 single venous grafts were performed. All patients were submitted to dipyridamole echocardiography testing before (range 1-3 days) and shortly after (range 5-7 days) myocardial revascularization, always with the patients off antianginal medication. An arbitrary wall-motion score grading from 0 to 3 (normal, hypokinesia, akinesia, and dyskinesia) was applied to the seven regions into which the left ventricle was divided. Before surgery 48 patients showed wall-motion abnormalities during the test (47 patients also presented ECG changes). Angina occurred in 48 patients. One patient had ischemic ECG changes and angina. The mean wall-motion score was 3.11 per patient before and 6.5 per patient after the test (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake.

125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. 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. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet.

Adult↗

Suitability of Doppler echocardiography for the assessment of right heart hemodynamics after De Vega tricuspid annuloplasty.

Cardiac Doppler Echocardiography is a suitable method for to evaluating right heart hemodynamics. However, the surgical correction of tricuspid valve annuloplasty changes valve geometry and might possibly lead to a technical obstacle to this estimation. The accuracy of Doppler echocardiography in the assessment of tricuspid regurgitation and systolic pulmonary pressure in patients who had undergone De Vega annuloplasty was evaluated in this study. Ten patients (9 females and 1 male), mean age 55.7 +/- 7.8 years, who had a previous De Vega annuloplasty for the treatment of tricuspid regurgitation due to a severe mitral stenosis, underwent a Doppler echocardiography study and, within two hours, right heart catheterization for a direct comparison of parameters calculated by different methods. Right ventricular-atrial maximal pressure gradient was found to be 32.6 +/- 11.07 mmHg by Doppler and 31.4 +/- 11.07 mmHg by catheterization. Pulmonary systolic pressure was 42.6 +/- 9.1 mmHg at Doppler and 39.1 +/- 11.3 mmHg at catheterization, with a highly significant correlation between the 2 techniques (r = 0.98%, p < 0.01). With semiquantitative Doppler evaluation 10 patients showed tricuspid insufficiency, which was mild in 8 and medium in 2. At catheterization all patients were found to have mild tricuspid insufficiency. Cardiac Doppler seems a reliable method in the evaluation of tricuspid regurgitation and of pulmonary systolic pressure even in patients who underwent De Vega annuloplasty.

Blood Pressure↗

Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark. Italian Multicenter Cardiomyopathy Study (SPIC) Group.

Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001).

Adolescent↗

Myocardial vitamin E is consumed during cardiopulmonary bypass: indirect evidence of free radical generation in human ischemic heart.

Although a role for free radicals in myocardial damage during cardiopulmonary bypass for open heart surgery has been postulated, direct evidence of free radical production as well as consumption of tissue antioxidants such as vitamin E is still lacking. Twenty patients (age 26-66 yr, mean 48) undergoing elective open heart surgery with moderate hypothermia, and cold crystalloid cardioplegia, were studied. Cardiopulmonary bypass time was 61.4 +/- 31.2 min. The specimens of atrial tissue collection before and after cardiopulmonary bypass, were immediately frozen in liquid nitrogen. Mean vitamin E atrial content, measured by reverse phase HPLC, was 355 +/- 249 pmol/mg of dry weight basally, 135 +/- 85 pmol/mg (p < 0.05) at the end of the ischemic period and 405 +/- 288 pmol/mg after the reperfusion period (p < 0.01). Microscopic examination of right atrial biopsies ruled out differences in fibrosis or cellular damage as the cause of vitamin E changes. Although a great basal variability in atrial vitamin E content was observed, which was independent of age, sex and clinical status, a reproducible and substantial decrease in atrial vitamin E content after cardiopulmonary bypass occurred (mean reduction 45 +/- 17% and 55 +/- 22%, respectively, after ischemia and after reperfusion). This was directly related to the aorta cross-clamping duration and partially to the minimum temperature achieved. In conclusion, apart from the great variability observed in basal vitamin E tissue content, vitamin E was always reduced during cardiopulmonary bypass, suggesting an oxidative stress on the myocardium during open heart surgery.

Adult↗

High dose aprotinin to reduce blood loss in patients undergoing redo open heart surgery.

Recently, aprotinin has been demonstrated to be effective in reducing post-operative bleeding after open heart surgery. The aim of this study was to evaluate the effectiveness of high dose aprotinin in patients undergoing redo open heart surgery in whom perioperative bleeding is generally increased. Fifty-eight patients, mean age 55 years, underwent a second open heart surgery for single valve replacement in 37 patients (mitral or aortic), for double valve replacement in 16 patients and for coronary artery by-pass grafting in 4 patients. In 30 of the 58 patients (Group A) aprotinin was infused with the following scheme: 2 million KIU in 30 minutes during induction of anesthesia, 2 million KIU in the priming volume of extracorporeal circulation and 500,000 KIU every hour until the end of the surgical procedure. The remaining 28 patients served as control group (Group B). No adverse reactions to aprotinin were observed. There was no significant difference in cardiopulmonary by-pass time and minimum temperature achieved between the two groups of patients. During the operative day blood loss was significantly lower in group A than in group B (492 +/- 336 ml vs. 628 +/- 273 ml) (p < 0.01). This difference was not significant during the following days. However 3 days after the operation a still significant difference was reported in total blood loss between group A and group B (816 +/- 507 ml vs. 1018 +/- 373 ml) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of dipyridamole-echocardiography test in the evaluation of coronary reserve after coronary artery bypass grafting.

The object of this study was to assess the usefulness of the dipyridamole-echocardiography test in the early evaluation of coronary artery bypass grafting, when the use of an exercise stress test is precluded. We studied 39 consecutive patients (37 men and two women, mean age 57.3 years) referred to our institute for elective coronary artery bypass. Five patients had single, 12 patients double, 20 patients triple vessel disease, and two had left main stem disease. Nineteen left internal mammary artery grafts, 20 sequential grafts, and 39 single vein grafts were performed. All the patients were subjected to the test before (time range 1 to 3 days) and after (time range 6 to 10 days) the operation in the absence of therapy. Dipyridamole was administered intravenously 0.56 mg/kg over 4 minutes (low dose); if no effect was apparent, an additional 0.28 mg/kg over 2 minutes (high dose) was given. During the test, blood pressure and a twelve-lead electrocardiogram were monitored. An arbitrary wall motion score was derived by dividing the left ventricle into six regions and grading from 0 to 3-normokinetic, hypokinetic, akinetic, and dyskinetic zones. Preoperatively the test was positive in 38 patients as evidenced by wall motion abnormalities (36 patients had electrocardiographic changes) and in one patient by electrocardiographic changes and chest pain; 22 tests were positive after the low dose and 17 after the high dose. Angina was present in 33 patients. Mean wall motion score was 1.64 per patient in the basal condition and 4.03 per patient after the test (p less than 0.001). After coronary bypass in three patients the test was positive at the same dosage that was used preoperatively, as shown by wall motion abnormalities (in two patients by electrocardiographic changes, as well). Four patients had symptoms. Furthermore, at 6 months' follow-up, a treadmill stress test performed in these three patients was positive for ischemia and angina. The wall motion score was 1.25 per patient in the basal condition and 1.53 per patient after the test (no significant difference). When the preoperative wall motion score obtained after dipyridamole echocardiography was compared with the postoperative score, a statistically significant difference was seen: 4.03 per patient versus 1.53 per patient (p less than 001). In eight patients we observed an improvement of basal myocardial contractility after the operation, which indicates the reversibility of wall motion abnormalities observed before coronary bypass. In conclusion our data show that the dipyridamole-echocardiography test is a suitable method for the early assessment of bypass grafting when other methods, exercise dependent, are not indicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗