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Biomedical subjects

A Biagini

Publications and source records attributed to A Biagini.

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

Distribution and subcellular localization of acylpeptide hydrolase and acylase I along the hog gastro-intestinal tract.

The distribution of acylase I and acylpeptide hydrolase along the hog small intestine was investigated. No significant changes in their respective specific activity was found when the intestine was cut off and divided into eight segments (taken every 200 cm) so as to specifically study the duodenum, jejunum and ileum. Upon performing subcellular fractionation of hog enterocytes, it was observed that acylpeptide hydrolase is a soluble enzyme, while acylase I is essentially a soluble protein accounting for only 5% of the activity associated with the whole membrane fraction. The membrane-bound acylase I was neither solubilized by phosphatidylinositol-specific phospholipase C from Bacillus cereus nor by detergents which are commonly used to solubilize alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein. When a phase separation was carried out in Triton X-114, all the anchored-membrane proteins of the intestinal membranes were located in the detergent-rich phase, while acylase I was present in the detergent-poor phase. Finally, the immunolabeling of intestinal cells with specific antibodies definitively established the cytoplasmic localization of acylase I. Acylpeptide hydrolase and acylase I therefore both are located in the enterocyte cytoplasm.

Amidohydrolases↗
PubMed1999

The flow-function relationship in patients with chronic coronary artery disease and reduced regional function: a Doppler transesophageal and bidimensional transthoracic echocardiography study.

BACKGROUND: Infra-low dose dipyridamole allows one to selectively explore myocardial viability. Transesophageal echocardiography Doppler measurement of left anterior descending coronary artery flow at baseline and following dipyridamole is an efficient tool to assess coronary flow response. Aim of this study was to determine the flow-function relationship during coronary vasodilatory stress in patients with coronary artery disease and baseline dysfunction. METHODS AND RESULTS: Twelve patients with resting dyssynergies and 6 controls underwent assessment of regional function and of left anterior descending blood flow velocity. Flow and function were evaluated at rest and following infra-low dose dipyridamole (0.28 mg/Kg over 4 min). Controls showed a normal function at rest and after dipyridamole. Six patients ('Responders') with resting dyssynergies showed an improvement in segments of left anterior descending artery territory, whereas the other six ones ('Non-responders') showed no functional change. Controls and 'Responders' had similar values of resting peak diastolic left anterior descending artery flow velocity both at rest and after dipyridamole, whereas 'Non-responders' showed a blunted flow response to dipyridamole. CONCLUSION: Myocardial segments with a resting dysfunction and a contractile reserve more often exhibit a residual flow response, whereas segments with fixed pattern show a flat flow response during coronary vasodilator stress.

Blood Flow Velocity↗
PubMed1998

Acute hemodynamic effects of endogenous adenosine in patients with chronic heart failure.

OBJECTIVE: The objective of this study was to assess the acute hemodynamic effects of endogenous adenosine accumulation in patients with chronic heart failure. Exogenously administered adenosine has been shown to reduce pulmonary vascular resistance and to increase cardiac index in normal subjects and in patients with pulmonary hypertension or end-stage biventricular heart failure. Endogenous adenosine accumulation can be provoked by dipyridamole. METHODS AND RESULTS: Ultra-low-dose dipyridamole (0.07 mg/kg/min for 4 minutes) was administered in 20 patients with either symptomatic idiopathic (n = 12) or ischemic (n = 8) dilated cardiomyopathy and reduced left ventricular ejection fraction (mean 25%+/-5%). Hemodynamic variables were measured before and within 1 minute from the end of dipyridamole infusion. After dipyridamole administration, a mild but significant increase in heart rate (4.5%; p = 0.03) and reduction in mean blood pressure (6.8%; p < 0.001) without changes in right atrial pressure (p = NS) were detected. Dipyridamole increased cardiac output by 26.6% (p < 0.001), cardiac index by 24% (p < 0.001), and stroke volume by 19.8% (p < 0.001), with concomitant 24.6% reduction of systemic vascular resistance (p < 0.001). Moreover, dipyridamole reduced mean pulmonary artery pressure by 8.3% (p < 0.01) and pulmonary vascular resistance by 33.3% (p = 0.001), without changes in pulmonary wedge pressure (p = NS). A significant correlation between percent decrease from baseline in pulmonary and systemic vascular resistance (r = 0.66; p = 0.002) was found after administration of dipyridamole. CONCLUSIONS: Endogenous adenosine accumulation induced by ultra-low-dose dipyridamole infusion acutely improves the hemodynamic profile, decreasing pulmonary and, to a lower extent, systemic vascular resistance and increasing cardiac index in patients with severe chronic heart failure.

Adenosine↗
PubMed1998

Preoperative assessment of coronary artery disease in aortic stenosis: a dipyridamole echocardiographic study.

BACKGROUND: The aim of this study was to establish the feasibility, safety, and diagnostic accuracy of the dipyridamole echocardiography test in patients with severe aortic valve stenosis for noninvasive detection of coexisting coronary artery disease. METHODS: The high-dose dipyridamole echocardiography test was performed in 52 patients with severe aortic stenosis; all patients also underwent coronary angiography, independent of test results, before cardiac operation. RESULTS: The dipyridamole echocardiography test was completed without major complications. One patient had transient atrial fibrillation that was reversed by aminophylline. Thirty-one patients (60%) had a negative test result; all had normal coronary arteries. Ten of the 21 patients (48%) with a positive test result had coexisting coronary artery disease. The positive predictive value of the dipyridamole echocardiography test for detection of coronary disease in patients with severe aortic stenosis was 48%. The negative predictive value was 100%. The sensitivity was 100% and the specificity was 74%. CONCLUSIONS: Dipyridamole echocardiography is a safe and feasible tool in patients with severe aortic stenosis eligible for a cardiac operation. A negative test result reliably rules out a significant stenosis, whereas a positive one is much less accurate in predicting coronary artery disease.

Aortic Valve Stenosis↗
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

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

The hog intestinal mucosa acylase I: subcellular localization, isolation, kinetic studies and biological function.

The soluble acylase I (N-acylamino acid amidohydrolase, EC 3.5.1.14) from hog intestinal mucosa was 11,000-fold purified for the first time using a new four-step procedure involving an immunoaffinity chromatography. The resulting protein, which had an isoelectric point of 5.2 and a M(r) of 90,000 was composed of two apparently identical N-acylated polypeptide chains. Its amino acid composition was comparable to that of hog kidney acylase I. The enzyme had a pH optimum at 8.0 and required Zn2+ or Co2+. The optimal temperature for the acylase reaction was 40 degrees C and the activation energy of thermodenaturation was estimated at 260 kJ mol-1. The enzyme was strongly inhibited when preincubated with chelating agents, by diethyl pyrocarbonate under histidine-modifying conditions as well as by sulfhydryl compounds. The reaction of the purified enzyme with the synthetic substrate furylacryloyl-L-methionine was partly characterized as follows: Km = 0.22 +/- 0.03 mM, kcat = 128.0 +/- 17.8 s-1 and kcat/Km = 5.8 +/- 1.6 x 10(5) M-1 s-1. The L-stereoisomer of methionine competitively inhibited the enzyme reaction with a Ki of 3.4 +/- 0.2 mM. It is suggested that acylase I might not only be involved in the catabolism of intracellular N-acylated protein but also be responsible for the biological utilization of N-acylated food proteins.

Amidohydrolases↗
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

Impact of culprit lesion morphology on prevalence of provoked myocardial ischaemia in patients with old myocardial infarction. A dipyridamole stress echocardiography, exercise electrocardiography and angiographic study.

We have recently shown that in patients with single vessel disease and no myocardial infarction, a complex plaque morphology makes myocardium more vulnerable to ischaemia during dipyridamole echocardiography testing. Whether coronary lesion morphology in the infarct-related artery in a chronic phase may also modulate prevalence of ischaemia in the same territory remains unknown. In order to determine the possible relationship between culprit lesion morphology in the infarct-related artery and the prevalence of homotopic ischaemia during stress tests, data from high dose dipyridamole echocardiography tests (up to 0.84 mg.kg-1 over 10 min), exercise electrocardiography and coronary angiography from 73 in-hospital patients with a previous myocardial infarction and patent infarct-related single-vessel disease (> or = 50% diameter reduction) were analysed. An angiographic culprit lesion was considered complex (Ambrose classification) when irregular borders, ulcers, thrombus and/or intraluminal lucencies were present. According to angiographic lesion morphology, two groups were identified: Group I, with simple-type culprit lesions; Group II, with complex type culprit lesions. Number of patients (I = 36; II = 37), age (I = 57 +/- II vs II = 55 +/- 9 years), ejection fraction (I = 58.8 +/- II 3 vs II = 56.5 +/- 10.2%), number of Q or non-Q wave myocardial infarctions, prevalence of rest angina (I = 9; II = II) or effort angina (I = 10; II = 10), culprit lesion stenosis severity (I = 57.9 +/- 7.2% vs II = 57.7 +/- 6.2% by computer analysis) and degree of infarct artery anterograde flow (I = 2.64 +/- 0.48 vs II = 2.56 +/- 0.50 by Thrombolysis in Myocardial Infarction definition) did not differ between the two groups (P = ns for all intergroup differences). Dipyridamole echocardiography test-induced ischaemia (considered as new or worsening abnormal wall motion) in the infarct-related artery territory was 25% in Group I and 59% in Group II (P < 0.01). Among positive dipyridamole echocardiography tests, low dose (0.56 mg.kg-1 over the 4 min) positivity occurred in two out of nine Group I patients and in 16 out of 22 Group II patients (22 vs 73%, P < 0.05). Exercise electrocardiography was positive in seven out of 32 Group I patients, and in 16 out of 35 Group II patients (22 vs 46%, P < 0.05). The peak rate pressure product tended to be higher in Group I than in Group II patients (282 +/- 65 vs 257 +/- 65 mmHg x beats.min x 10(2), P = 0.07). Thus, in patients with previous myocardial infarction and a patent infarct-related artery, complex culprit lesion morphology is associated with a higher prevalence of ischaemia and a lower ischaemic threshold during both exercise and dipyridamole stress testing. The morphology of culprit stenosis is important in modulating different stress responses in the chronic phase of myocardial infarction.

Adult↗
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↗
PubMed1996

Ambulatory follow-up of aortic dissection: comparison between computed tomography and biplane transesophageal echocardiography.

UNLABELLED: Aim of the study was to assess the relative usefulness of transesophageal echocardiography (TEE) and X-ray computed tomography (CT) in the follow-up of patients who survived an aortic dissection. MATERIALS AND METHODS: We evaluated 44 patients (age = 57 +/- 12 years) with treated aortic dissection: 14 had a De Bakey type I, 20 a type II and 1 patient a type III dissection treated surgically: 1 patient had a type I, 1 a type II and 7 a type III dissection treated medically. All entered an outpatient follow-up program with serial evaluations at 1, 6 and 12 months after initial diagnosis by dual noninvasive imaging protocol. A contrast-enhanced CT scan and a TEE with biplane probe were performed on the same day and in random order. RESULTS: A total of 252 evaluations with both CT and TEE were considered. A completely normal study was found in 45 TEE and 48 CT evaluations. The following abnormal findings could be documented by one or both techniques: thrombus in the false lumen (TEE: n = 48; CT: n = 45 evaluations); intimal flap (TEE and CT: n = 68); aortic dilatation (TEE and CT: n = 15); pericardial effusion (TEE and CT: n = 3); aortic pseudoaneurysm (TEE: n = 2; CT: n = 3); isthmic coarctation (TEE and CT: n = 1). Regarding the presence or absence of these abnormalities, which are within the diagnostic domain of both imaging techniques, the results were fully concordant in 245 studies, and discordant in 7, with an overall agreement of 97%. In addition, some abnormal findings could be detected by TEE only: aortic insufficiency (n = 36); intimal tear (n = 25); spontaneous echocontrast effect in the false lumen (n = 39 evaluations). Other abnormal findings could be detected by CT only: a pleural effusion in 4, a truncus anonymous dissection in 1, a pseudoaneurysm due to suture dehiscence of the distal anastomosis of the ascending aorta in 1 evaluation (which yielded ambiguous results by TEE, with turbulent flow departing from the graft). CONCLUSION: Both CT and TEE are atraumatic, safe and accurate techniques for serial follow-up imaging of patients treated for aortic dissection. Information provided by CT is largely redundant, rather than additive, to that provided by TEE. The latter should be probably preferred for shorter imaging time, accuracy and convenience, although CT might still play a role in selected cases of ambiguous TEE results.

Adult↗
PubMed1996

Normalization of peripheral thyroid hormone metabolism induced by successful chronic amiodarone treatment in patients with ventricular arrhythmias.

Amiodarone, an antiarrhythmic agent, is also known to have important effects on the peripheral metabolism of thyroid hormones; the relationship between these two effects of the drug, however, is not well established. We tested the hypothesis that the antiarrhythmic effect of amiodarone might be mediated by its effect on the metabolism of thyroid hormones. Peripheral thyroid hormone metabolism was investigated using a double-tracer ([125I]-T4 and [131I]-T3) procedure in 10 normal volunteers and 10 euthyroid patients with complex ventricular arrhythmias before and during 6 months' amiodarone treatment. The underlying cardiac disease was coronary artery disease in four cases, dilated cardiomyopathy in three and idiopathic arrhythmias in three. In all but one patient with complex ventricular arrhythmias amiodarone treatment resulted in a reduction of > or = 80% of premature ventricular contractions and complete suppression of episodes of ventricular pairs or ventricular tachycardia. In all cases successful treatment with amiodarone was accompanied by normalization of all kinetic parameters: T4 to T3 conversion ratio and T3/T4 molar ratio of production decreased to mean values of 24.7 +/- 17.5% and 0.35 +/- 0.22% respectively, whereas T4 production rate increased (mean value 75.9 +/- 30.0 nmol day-1 m-2). Our kinetic data indicate that long-term therapy with amiodarone, when effective in suppressing cardiac arrhythmias, also reduces peripheral T4 to T3 conversion, hence restoring the normal peripheral thyroid hormone metabolic pattern. In conclusion, our study confirms that the antiarrhythmic action of amiodarone may be (at least partially) mediated by its action on thyroid hormone metabolism, and may justify the hypothesis that an altered peripheral metabolism of thyroid hormones may play a role in the pathogenesis of complex ventricular arrhythmias.

Aged↗
PubMed1996

Mechanisms of regional ischaemic changes during dipyridamole echocardiography in patients with severe aortic valve stenosis and normal coronary arteries.

OBJECTIVE: Vasodilator stress echocardiography can cause myocardial ischaemia in patients with severe aortic valve stenosis and angiographically normal coronary arteries. The aim of the study was to determine the mechanism of ischaemia in this clinical model. METHODS: The study group comprised patients with severe aortic valve stenosis and normal coronary arteries: 25 patients (17 males, eight females; age 63 (SD 11) years) underwent a high dose (up to 0.84 mg/kg over 10 min) dipyridamole echocardiography test both before (2-4 d) and after (10-15 d) aortic valve replacement. Mean aortic pressure gradient was 96 (15) mm Hg, with a left ventricular mass index of 228 (49) g/m2. The dipyridamole echocardiography test was well tolerated and interpretable in all patients. RESULTS: Dipyridamole infusion induced chest pain in seven patients before and in no patient after surgery (28 v 0%, P < 0.01), ST segment depression in 12 patients before and two after surgery (48 v 8%, P < 0.01), and a transient regional dyssynergy in 10 patients before and two after surgery (40 v 8%, P < 0.01). In the preoperative evaluation, patients with an echocardiographically positive dipyridamole echocardiography test were comparable with patients with negative test as far as left ventricular mass index [240 (67) v 230 (64) g/m2, NS] and mean aortic pressure gradient [95 (22) v 92 (21) mm Hg, NS] were concerned. When compared to the preoperative assessment, the resting echo assessment in the postoperative evaluation showed unchanged values of left ventricular mass index [pre 228 (49) g/m2 v post 220 (36) g/m2, NS], but markedly decreased values of mean aortic gradient [pre 95 (15) mm Hg v post 22 (5) mm Hg, P < 0.01] and left ventricular wall stress index [pre 134 (30) g/cm2 v post 89 (19) g/cm2]. CONCLUSIONS: Dipyridamole echocardiography is a suitable clinical technique for assessing the ischaemic vulnerability of the left ventricle in severe aortic valve stenosis with angiographically normal coronary arteries. The frequent disappearance of the ischaemic response early after aortic valve replacement suggests that haemodynamic factors such as compressive diastolic wall stress or afterload reduction are important components of myocardial ischaemic vulnerability under these circumstances.

Adult↗
PubMed1996

Quantitative assessment of coronary atherosclerotic plaque profile by morphometric analysis of angiographic images.

Coronary plaque morphology (simple or complex) has a recognized clinical, pathophysiologic, and prognostic importance, but its routine use is hampered by the subjective and qualitative nature of the assessment. The aim of this study was to assess the feasibility and accuracy of mathematical, objective, operator-independent assessment of plaque morphology, by means of algorithms based on vector and fractal analysis, previously developed for describing continuous curves. Twenty coronary angiograms were analyzed: 10 with "simple-type" stenosis (defined according to Ambrose type I pattern, Group I) and 10 with "complex-type" stenosis (Ambrose type II pattern, Group II). Five morphometric parameters effectively separated simple and complex-type stenosis: peaks/cm (Group I = 0.24 +/- 0.31 vs Group II = 2.46 +/- 1.83, P < .01); summed maximum error/cm (I = 0.94 +/- 1.19 vs II = 4.53 +/- 0.56, P < .01); integrated error/cm (I = 0.22 +/- 0.27 vs II = 2.25 +/- 1.68, P < .01); number of features/cm (I = 0.02 +/- 0.05 vs II = 1.19 +/- 0.65, P < .01); standard deviation curvature (I = 0.07 +/- 0.01 vs II = 0.22 +/- 0.21, P = 0.06). The scaled edge-length ratio-the only parameter based on fractal analysis-was not different between the two groups (I = 1.03 +/- 0.01 vs II = 1.13 +/- 0.10, P = ns). Hence, a quantitative description of plaque morphology is feasible and allows an effective discrimination of simple and complex plaque profiles with morphometric parameters based on vector analysis.

Coronary Angiography↗