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Biomedical subjects

M Landolina

Publications and source records attributed to M Landolina.

13 recordsLinked to original sources
PubMed1992

Identification of propafenone metaboliser phenotype from plasma and urine excretion data.

The aim of the study was to validate a test based on analyses of urine to identify the propafenone metaboliser phenotype during routine chronic therapy. Twenty seven patients chronically treated with propafenone were studied. A debrisoquine test was performed in 10. Propafenone and its metabolites in plasma and urine were measured by HPLC. Propafenone, 5-hydroxypropafenone and N-depropylpropafenone concentrations in plasma were 1.09, 0.182 and 0.101 ng.ml-1, respectively. Total recovery of the administered dose in urine was 30.7%. Two patients were identified as PM, based on the result of the debrisoquine test (log D/4OHD of 1.26 and 1.36). This finding was confirmed by the propafenone metabolic ratio in urine, but the plasma data did not permit clearcut separation of the phenotypes. Propafenone/5-hydroxypropafenone in plasma was not a good predictor of metabolizer phenotype. Although the number of patients who completed all three tests was limited, it is concluded that analysis of propafenone/5-hydroxypropafenone in urine collected between two consecutive doses at steady-state is more practical than the debrisoquine test and more specific than determining the propafenone/5-hydroxypropafenone ratio in plasma, for identification of the propafenone metaboliser phenotypes.

Adolescent↗
PubMed1992

Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease. Antiarrhythmic Drug Evaluation Group.

To assess the spontaneous variability of ventricular arrhythmias after withdrawal of apparently successful antiarrhythmic therapy, we enrolled in a washout protocol 40 patients who had completed a randomized controlled 2-year study of antiarrhythmic drugs (the Antiarrhythmic Drug Evaluation Group [ADEG] study). All of them had heart disease and were first seen with high-grade ventricular arrhythmias (Lown class 4a and 4b) at enrollment. After 2 years all of them had responded to propafenone or flecainide; patients who completed the study on a regimen of amiodarone were not considered for the washout study. A total of 27 patients discontinued flecainide and 13 propafenone. Seven days after withdrawal they underwent 24- or 48-hour ECG testing and were classified as true responders (TR) if the arrhythmias were present at the same level as 2 years previously and false responders (FR) if they were below the ADEG responsiveness level. TR patients had a third 24-hour ECG 7 days later, after rechallenge with the same treatment, and FR patients had a third ECG without drugs. Adherence to the protocol was ascertained by measuring drug plasma concentrations at every 24-hour ECG recording. No differences were found in distribution of heart disease and grade of ventricular arrhythmias between patients in the washout study and the remaining group of the ADEG trial. Twenty-four of 40 patients (60%) were true responders. In 4 of the 17 patients who had a third 24 hour ECG, the responsiveness to the same drug was not confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1988

Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration.

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

Adult↗
PubMed1986

Body surface potential maps in old inferior myocardial infarction. Assessment of diagnostic criteria.

We assessed the accuracy of criteria for diagnosing an inferior myocardial infarction from body potential maps. Body surface potential maps were recorded from 140 lead points on the entire chest surface in three groups of subjects: group A consisted of 15 patients with an old inferior myocardial infarction and typical electrocardiographic signs of necrosis; group B consisted of 15 patients with an old inferior myocardial infarction, but without electrocardiographic signs of necrosis (inferior myocardial infarction was documented during the acute phase); group C consisted of 30 healthy controls. In each subject body surface potential distributions were examined every 2 msec of the QRS complex. Moreover, the potential-time integrals relating to three intervals (QRS, the first 20 and the first 40 msec of the QRS complex) were calculated at each lead point and transferred to diagrams representing the thoracic surface explored (isointegral maps). For each time interval, the mean isointegral map obtained from group C subjects was subtracted from the isointegral map of each patient. The value obtained at each lead point was then divided by the standard deviation of the normal values for that point; the resulting values indicating the standardized differences from normal values were transferred to another map (deviation index isointegral map, DI map). We considered a reliable index of inferior myocardial infarction an area where the time-integral values were at least 2 SD lower than normal, in the inferior half of the thorax. A number of variables relative to instantaneous potential distribution and to isointegral maps were considered. The DI maps of the first 40 msec of QRS gave the most accurate criteria; in fact, an area of negative values 2 SD lower than normal was found in all group A patients and in 11 out of 15 group B patients (sensitivity 100% in group A, 73% in group B and specificity, 83%). Thus our results indicate that body surface potential maps have greater diagnostic information content than the 12 standard electrocardiographic leads and demonstrate the usefulness of the time integral analysis of body surface potentials for diagnostic interpretation.

Adult↗
PubMed1986

Evidence for an inhibition of thyroid hormone effects during chronic treatment with amiodarone.

The effects of chronic amiodarone treatment on several thyroid and cardiac function parameters were studied in 50 euthyroid patients with refractory ventricular arrhythmias, divided in responders and nonresponders according to their sensitivity to the antiarrhythmic action of the drug. No differences in the severity of cardiac disease and blood amiodarone concentrations were found in the two groups. Amiodarone induced a significant inhibition of peripheral T4 monodeiodination, more pronounced in responders compared to nonresponders. On the contrary, only in responsive patients, elevated basal and TRH-stimulated TSH levels were observed (despite serum T3 levels were not different from those in nonresponders) and the indirect indices of cardiac performance, particularly the systolic time intervals, fell in a range usually observed in the hypothyroid states. These findings suggest that amiodarone, besides the well-known inhibition of T4 to T3 conversion, also induces a partial resistance to the thyroid hormones, which is probably involved in the therapeutical effectiveness of the drug.

Adolescent↗
PubMed1984

Side effects during therapy with low dosage amiodarone.

Amiodarone is a very active antiarrhythmic agent, but true incidence of Amiodarone-related side effects is still questionable. In a prospective trial of 400 or 200 mg of Amiodarone day for 56 days in 58 patients, we monitored thyroid and liver function, blood count, chest x-ray, ecg. In addiction we took regularly notice of subjective disturbances and physical signs. Side effects were: conduction disturbances 6%, bradycardia less than 50/min. 2%, gastrointestinal 12%, sleep disorders 12%, hyperthyroidism 4,15% and hypothyroidism 6.25%. Blood levels of Amiodarone and desethylamiodarone were not predictive of side effects. Noteworthy was the absence of cutaneous and pulmonary side effects. On the other hand, thyroid function should be monitored carefully because disfunction is not rare (10.4%) and in the case of hyperthyroidism could be related to worsening of arrhythmias.

Adolescent↗
PubMed1982

Limits of precordial electrocardiographic mapping in assessing anterior myocardial infarction size.

Purpose of our investigation was to ascertain whether the electrocardiographic mapping of the anterior thoracic wall can provide more precise information on the extent of an anterior myocardial infarction (MI) than the 12 conventional leads do. Thirty-seven patients were studied 1 to 72 months after an acute MI of the anterior wall. All patients underwent left heart catheterization which included selective coronary arteriography and left ventriculography, to evaluate the indication for surgery. Electromaps were obtained by means of 71 Ag-AgCl electrodes located at regular intervals on the thoracic wall (between the right midclavicular line and the left posterior axillary line). The following parameters were considered: total number of Q waves, R waves and ST elevations greater than or equal to 0.05 mV (NQ, NR, NST); the sum of Q, R and ST voltages (sigma Q, sigma R, sigma ST); the sum of Q-wave and R-wave areas (sigma aQ, sigma aR). The electrocardiographic data were correlated with the percentage of left ventricular dyssynergy (corresponding to the ratio between the length of the akinetic and/or dyskinetic portion of the left ventricular silhouette and the total enddiastolic perimeter) and with the ejection fraction obtained from the left ventricular angiograms in right anterior oblique projection. A significant but weak correlation was found only between sigma R, sigma aR and percentage of dyssynergy and between NST, sigma ST and ejection fraction. Thus the amplitude and duration values of positive activation potentials (sigma aR, sigma R) were better predictors of dyssynergy extent than the classical direct signs of necrosis (NQ, sigma Q). The poor correlation observed in our patients between ECG and angiographic data can mainly be due: a) to a lack of concordance between the dyssynergic area and the truly infarcted region; b) to the well-known limits of surface electrocardiography in defining the cardiac generator characteristics. In particular, as far as the adequacy of various ECG recording systems in determining infarct size is concerned, our study suggests that exploring a large thoracic area is not definitely more advantageous than using 12 - lead ECG, when only traditional analysis of electrocardiographic tracings is performed.

Adult↗
PubMed1981

Effect of nitroglycerin on ST potentials in the post-acute phase of myocardial infarction.

Thoracic electromaps were recorded before and after sublingual nitroglycerin (NG) in 26 subjects 15 and 30 days after acute myocardial infarction (MI), in order to evaluate the effect of the drug on injury potentials. Ten patients with documented left ventricular aneurysm were also studied 5 to 46 months after acute MI. Fifteen min after NG there was a significant decrease, compared with basal values, of ST segment elevations, blood pressure and rate-pressure product on both the 15th and 30th days. The degree of ST potentials reduction was not strictly related to the decrease of myocardial oxygen consumption, as indicated by the rate-pressure product. The response to NG on the 15th day did not predict accurately the evolution of injury potentials. In fact there was no significant correlation between percentages reduction of ST after NG on the 15th day and amplitudes of ST segment elevations present on the 30th day. In the patients with ventricular aneurysm, ST potential decrease and hemodynamic changes after NG were similar to those observed in the other groups studied. Our data suggest that it is not possible to differentiate between ST segment elevations associated with a dyssynergic area and those merely due to ischemic injury on the basis of NG sensitivity, and that ST segment elevations in the acute and subacute phase and long after MI have, at least in part, a similar electrophysiological significance.

Adult↗