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Biomedical subjects

C Libersa

Publications and source records attributed to C Libersa.

89 records · Page 5Linked to original sources
PubMedDate not supplied

Doppler flow wire evaluation of renal blood flow reserve in hypertensive patients with normal renal arteries.

PURPOSE: To study the vasomotor responses of the renal microcirculation in patients with essential hypertension. METHODS: We studied the reactivity of the renal microcirculation to papaverine, with intraarterial Doppler and quantitative arteriography, in 34 renal arteries of 19 hypertensive patients without significant renal artery stenosis. Isosorbide dinitrate was given to maximally dilate proximal renal arteries. APV (average peak blood flow velocity) was used as an index of renal blood flow. RESULTS: Kidneys could be divided into two distinct subgroups based on their response to papaverine. An increase in APV of up to 55% occurred in 21 kidneys, an increase > 55% in 13 kidneys. Within each group the values were normally distributed. Both baseline APV and the effect of papaverine on mean velocity differed significantly between groups. CONCLUSION: There seems to be a subgroup of patients with essential hypertension that has an impaired reactivity to papaverine, consistent with a functional impairment of the renal microcirculation. Further studies are required to determine whether this abnormality contributes to or results from elevated blood pressure.

Analysis of Variance↗
PubMedDate not supplied

Study of circadian melatonin secretion pattern at different stages of Parkinson's disease.

To explore changes in melatonin secretion patterns and biologic rhythms in Parkinson's disease patients with or without levodopa-related motor complications (LDRMCs), the authors investigated, in an observational study, circadian rhythms of central temperature, motor activity, plasma cortisol, and melatonin in three groups: de novo untreated patients (group I), patients treated with levodopa + dopamine agonist and without LDRMCs (group II), and patients treated with levodopa + dopamine agonist and with LDRMCs (group III). There were no differences among the three groups for the rhythm of temperature, motor activity, or plasma cortisol. There was a significant (p < 0.05) phase advance in plasma melatonin secretion in patients receiving a dopaminergic treatment compared with untreated patients. The daytime area under the curve (AUC) was increased significantly in group III, and the nighttime AUC-to-daytime AUC ratio of melatonin secretion decreased significantly in group III, suggesting that the nychthemeral pattern of melatonin secretion was changed in patients with LDRMCs. Comparison of the three groups suggests a slight but insignificant phase advance and amplitude decrease of circadian melatonin secretion related to both evolution and treatment of Parkinson's disease. Despite the lack of a global desynchronization in other circadian biologic rhythms, the circadian secretion pattern of melatonin is modified in patients with LDRMCs.

Aged↗
PubMedDate not supplied

Electrophysiological effects of dofetilide in an in vitro model of "border zone" between normal and ischemic/reperfused myocardium.

BACKGROUND: To evaluate both class III activity and antiarrhythmic action of dofetilide at the level of the "border zone," we investigated its electrophysiological effects on guinea pig ventricular strips submitted partly to normoxia (normal zone, NZ) and partly to simulated severe ischemia, then reperfusion (altered zone, AZ). METHODS AND RESULTS: Because of the differential class III effects of dofetilide in normal and ischemic regions, the dispersion of the action potential duration at 90% repolarization (APD(90)) between NZ and AZ was reduced by 5 nmol/L of drug during early ischemia (at 10 minutes, APD(90) NZ/APD(90) AZ was 1.68+/-0.22 versus 2.82+/-0.17 in control, P<0.05), whereas 50 nmol/L dofetilide worsened it during late ischemia (at 30 minutes, APD(90) NZ/APD(90) AZ was 4.62+/-0.76 versus 2.57+/-0.21 in control, P<0.05). Concomitantly, dofetilide at 5, 10, and 50 nmol/L abolished the early extrastimulus (ES)-induced arrhythmias, and at 10 and 50 nmol/L, it significantly enhanced the incidence of late spontaneous repetitive responses (in 86% and 75% of preparations treated with 10 and 50 nmol/L, respectively, versus 25% in control, P<0.05). During reperfusion, dofetilide at 5, 10, and 50 nmol/L exhibited concentration-dependent class III effects, as it did in the NZ, and did not modify the incidence of spontaneous arrhythmias. CONCLUSIONS: Dofetilide 5 nmol/L decreased APD(90) dispersion between NZ and AZ and reduced the early ES-induced arrhythmias. However, dofetilide 50 nmol/L increased APD(90) dispersion, and at 10 and 50 nmol/L, it increased the late spontaneous arrhythmias.

Action Potentials↗
PubMedDate not supplied

Adverse cardiovascular effects of anti-arrhythmia drugs. Part I: Proarrhythmic effects.

Antiarrhythmic drugs are able to save patients from emergency dysrhythmic situations or to avoid symptomatic disorders when used in a prophylactic goal. However they can also induce adverse effects. Cardiovascular adverse effects, and especially proarrhythmic effects, are the most dreaded. Analysis of the underlying mechanisms of the onset and perpetuation of sustained arrhythmias could lead to a better understanding of causes of proarrhythmic effects and thus to a limitation of their occurrence. Antiarrhythmic drugs can modulate the three principal factors which are involved in the onset of arrhythmias: individual predisposing factors, trigger mechanisms and environmental factors. This multiparameter modulation will conduct either to suppress the arrhythmic disorders (antiarrhythmic effect) or to impair it (proarrhythmic effect). According to the numerous factors which take part in the onset and perpetuation of arrhythmia, incidence of proarrhythmic effect of antiarrhythmic drugs is very difficult to evaluate.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Adverse cardiovascular effects of anti-arrhythmia drugs. Part II: Inotropic effects and specific pharmacokinetic properties.

The antiarrhythmic drugs are unfortunately not devoid of adverse effects. A good watching of their safety is necessary, according to their cardiovascular adverse effects which are the most dreaded. Among these and beside the proarrhythmic effects, the negative inotropic effects can impair cardiac function. Different mechanisms could explain the negative inotropic effects of antiarrhythmic drugs: reduction of adrenergic sensitivity, decrease of calcium concentration in the cardiac cells. Pharmacokinetic properties of antiarrhythmic drugs can modulate their cardiovascular adverse effects. As a matter of fact the plasmatic concentration of the unbound drug, which could be correlated to the adverse effects, fluctuates according to the protein binding of the drug. In an other way the first pass hepatic effect of a drug can be saturable so that the resulting dose-concentration curve becomes exponential. Drug disposition might also be very different from one patient to another depending on kidney and/or hepatic function and genetically determined metabolic pathways.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Mexiletine metabolism in vitro by human liver.

Human livers were used in investigations of mexiletine biotransformation in vitro. The major metabolic pathways of mexiletine oxidation, to form hydroxymethylmexiletine (HMM) and p-hydroxymexiletine (PHM), were characterized in liver cell preparations. The localization of reactions in the microsomal fraction, their heat lability, NADPH requirement and inhibition by prototype cytochrome P-450 (P-450) inhibitors (CO, SKF 525-A, metyrapone and quinidine) implied that they were catalyzed by P-450. Kinetic studies of reactions were performed in microsomes from five different livers. Eadie-Hofstee plots of data gave no indication of systematic deviation from linearity, suggesting that over the range of mexiletine concentrations examined (3.3-133.3 microM), HMM and PHM were formed by a single enzymatic site. Within a liver preparation, Km and Vmax values for HMM and PHM formation were similar. Between livers, Km values of reactions were similar with only a 1.8-fold range for each reaction, whereas Vmax values showed 7.2- and 7.8-fold ranges for HMM and PHM production, respectively. There was a very strong correlation between Vmax values for both reactions. These results, coupled with a parallel effect of inhibitors (SKF-525A, metyrapone, alpha-naphtoflavone and quinidine) on HMM and PHM formation, argue that both reactions are mediated by a common P-450 or closely related isozymes. In addition, the present in vitro results support the hypothesis that the genetically variable P-450 db 1 isozyme catalyzes the oxidation of mexiletine.

Biotransformation↗
PubMedDate not supplied

[Vascular effects of dihydropyridines].

Dihydropyridines are the most numerous available calcium antagonists. While belonging to the same group these drugs have physical, chemical, pharmacokinetic or pharmacodynamic properties which are sometimes specific and can explain differences in the targets and the vascular selectivity. These properties can be related to lipophilic or hydrophilic characteristics, existence or lack of 'use-dependence', possible liaison to membrane phospholipids, and differences in elimination half lives. Selectivity of dihydropyridines also depends on the nature of the target structure (amount of intra-cellular calcium storage and mechanism of its release, electrophysiological properties of these cells) and of its pathological state (atherosclerosis and/or hypertension). Some of these properties could explain the anti-atherogenic effects, myocardial impact, cerebral and renal vascular flow and action in some pathological situations (Raynaud's syndrome, chronic arteriopathy, migraine...). A better knowledge of these different properties could lead to a more accurate choice of the drugs and to a decrease in the incidence of their side effects.

Blood Vessels↗
PubMedDate not supplied

[Methods of antiarrhythmic drug evaluation in man].

Antiarrhythmic drugs (AA) are useful in some critical situations but their use remains questionable. Evaluation of their efficacy and possible side effects required accurate knowledge of various methods. ECG gives relevant informations on the conduction intervals alterations caused by AA. Holter monitoring allows evaluation of the efficacy and/or proarrhythmic effects throughout 24-48 hour periods provided that spontaneous variability is taken into account. Ambulatory sequential loop ECG allows a longer monitoring of treatment in patients with symptomatic arrhythmias. Provocative electrophysiological testings give good evaluation of AA efficacy in some supraventricular or ventricular arrhythymias but predictivity of efficacy or proarrhythmic effects is sometimes problematical. Use of effort testing is limited to evaluation of antiarrhythmic effects of drugs in major dysrythmias and in some frequency-dependent dysrythmias, but this technique allows also detection of proarrhythmic incidence in those extremely altered autonomic nervous system tone. Other techniques of evaluation (Signal averaged ECG, automatic implantable cardiovecter defibrillator with holter monitoring, drug plasma concentration monitoring) are still under discussion.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

[Antagonists of calcium movements and rhythm disorders].

Since transmembrane myocardiac calcium-exchanges play an important role in myocyte electrogenesis as well as in triggering and maintenance of some cardiac arrhythmias, it might be true that calcium antagonists possess antiarrhythmic properties. However, use of calcium antagonists as antiarrhythmic agents is only possible if the drug is devoid of sympathetic reflex stimulation and possesses use-dependence properties. These drugs are of most efficiency in cardiac arrhythmias (especially of supraventricular origin), caused by reentry phenomena in which part of the circuit is governed by calcicosodic cells. The use of calcium antagonists for ventricular arrhythmias is limited to some specific indications (idiopathic ventricular tachycardia with right bundle branch block and left axis, reperfusion arrhythmias...). Choice of the type and the route of administration of calcium antagonists has to take into account their pharmacokinetic specificities which can alter their antiarrhythmic potency.

Arrhythmias, Cardiac↗