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Biomedical subjects

S Lévy

Publications and source records attributed to S Lévy.

At least 37 records · Page 2Linked to original sources

Plasma beta-endorphin and adenosine concentration in pulmonary hypertension.

To determine whether beta-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and beta-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 +/- 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 +/- 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 +/-5 mm Hg). Plasma beta-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher beta-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (-60% in COPD [p <0.005] and -70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and beta-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between beta-endorphin and adenosine concentrations (r = -0.751, p <0.001): the higher the adenosine, the lower the beta-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased beta-endorphin release.

Adenosine↗

Spontaneous episodes of atrial fibrillation after implantation of the Metrix Atrioverter: observations on treated and nontreated episodes. Metrix Investigators.

OBJECTIVES: We sought to evaluate the number and duration of device-treated and self-terminating, nontreated episodes of atrial fibrillation (AF) after implantation of the Metrix Atrioverter. BACKGROUND: A recent study has shown that the Atrioverter can rapidly restore sinus rhythm in patients with AF; however, the effect of the device on the clinical course of the arrhythmia in these patients is unknown. METHODS: The Atrioverter was implanted in 51 patients with symptomatic, recurrent, drug-refractory AF. The device was programmed to periodically monitor the cardiac rhythm. Defibrillation of AF episodes was performed under physician observation. RESULTS: During a mean follow-up of 260 +/- 144 days, 1,161 episodes of AF were observed during valid monitoring periods in 45 of 51 patients. Forty-one patients experienced 231 episodes for which they sought defibrillation therapy. The average duration of the treated episodes during valid monitoring periods (190 of 231 episodes in 39 of 41 patients) was significantly longer than that of the nontreated episodes (38 +/- 44 vs. 10 +/- 8 h; p < 0.05). The time between episodes requiring Atrioverter therapy increased, and the risk of having an episode requiring treatment decreased. No changes were observed in the number and duration of the short-lasting, nontreated episodes as time since implantation of the device increased. CONCLUSIONS: In patients with symptomatic, recurrent, drug-refractory AF, the frequency of long-lasting episodes, which were treated under observation with repeated defibrillation using the Atrioverter, decreased. The number and duration of short-lasting, nontreated episodes did not change during the 20-month study period. The effect of ambulatory use of the device on the recurrence of short-lasting episodes needs to be evaluated.

Adult↗

Classification system of atrial fibrillation.

A number of publications and clinical trials on the management of atrial fibrillation (AF) deal with this arrhythmia as if it represents a single entity. As a result, advances made in recent years have not affected the way AF patients are treated in general practice except, perhaps, for the use of warfarin in anticoagulation. Therefore, there is a need for a classification system and for uniformity in the nomenclature used. The two terms currently used to describe AF, paroxysmal and chronic, require a time frame. It is proposed that if an AF episode lasts longer than 7 days, the condition should be considered chronic. For the first symptomatic, non-self-terminating episode that is fewer than 7 days long, the term recent onset AF may be used, or recent discovery if the AF is asymptomatic or if the duration cannot be determined. Attacks of paroxysmal AF may differ in their duration, frequency, and functional tolerance. In the classification system described, three clinical aspects of paroxysmal AF were isolated in such a way as to have implications for therapy. This classification system was found to be useful for characterizing different subsets of patients with AF.

Anti-Arrhythmia Agents↗

Specific up-regulation of mitochondrial F0F1-ATPase activity after short episodes of atrial fibrillation in sheep.

INTRODUCTION: Ventricular fibrillation induced by either digitalis intoxication or electrical stimulation is reported to alter myocardial energy by impairing the sarcolemmal Na,K-ATPase or the receptor for digitalis and the mitochondrial ATPase synthase or F0F1-ATPase. However, little is known about these membrane functions during atrial fibrillation (AF). METHODS AND RESULTS: We analyzed the effects of electrically induced AF on biochemical activities of atrial F0F1-ATPase and Na,K-ATPase in sheep. A group of six sheep was subjected to direct short electrical stimulation of the right atrium to induce AF. Sham-operated sheep served as a control group. Microsomal and mitochondrial membranes of atrial muscle were isolated and tested for enzymatic activity. All paced sheep developed multiple episodes of sustained AF, with a mean total duration of 110 minutes over a 2-hour period. Data showed that short-term pacing-induced AF significantly activated membrane F0F1-ATPase activity (P < 0.05) without changes in cytochrome-c oxidase activity, Na,K-ATPase activity, ouabain sensitivity, and alpha1-subunit expression. CONCLUSION: Specific activation of F0F1-ATPase activity is an early molecular consequence of sustained AF in sheep.

Animals↗

Inhibition of Na,K-ATPase by external electrical cardioversion in a sheep model of atrial fibrillation.

INTRODUCTION: Electrical external cardioversion commonly used to treat atrial fibrillation (AF) is associated with myocardial membrane damage and disturbances in ionic homeostasis (hemodynamically unstable). The present study was designed to investigate whether alterations in ionic homeostasis observed were due in part to changes in the myocardial activity of Na,K-ATPase. METHODS AND RESULTS: AF was induced by pacing in ten anesthetized sheep divided into two groups. Group I (n = 4) received a single external countershock of 360 J after three episodes of AF lasting 10 minutes. Group II (n = 6) served as controls. Activity, responsiveness to ouabain, and membrane expression of catalytic alpha and beta subunits of Na,K-ATPase in sarcolemmal myocardial membrane fractions were investigated. Membrane fluidity and fatty acid composition, and plasma levels of atrial natriuretic factor (ANF) also were measured. One shock after episodes of AF significantly decreased ventricular Na,K-ATPase activity up to 50% (P < 0.001) without modification of atrial activity at the membrane level. Sites with low affinity to ouabain showed a fivefold lower affinity for ouabain in the cardioversion group than in the control group (IC50 = 7.9 micromol/L vs 40 micromol/L ouabain, P < 0.05). Plasma levels of ANF were significantly increased in the cardioversion group compared with the control group. These changes were independent of membrane modulation in terms of expression of Na,K-ATPase, membrane fluidity, and fatty acid composition. CONCLUSION: This study suggests that left ventricular perturbation of ionic homeostasis subsequent to transthoracic cardioversion could result from inactivation of Na,K-ATPase activity.

Animals↗

Characterization of different subsets of atrial fibrillation in general practice in France: the ALFA study. The College of French Cardiologists.

BACKGROUND: The clinical presentation and causes of atrial fibrillation (AF) in the 1990s may differ from AF seen 2 to 3 decades ago. It was the objective of this prospective study to characterize various clinical presentations and underlying conditions of patients with AF observed in general practice in France. METHODS AND RESULTS: The study population comprised 756 patients (19 to 95 years of age) with electrocardiographically documented AF subdivided into paroxysmal (<7 days), chronic (last episode >1 month) and recent onset AF(persistent >7 days and<1 month). Symptoms were present in 670 patients (88.6%). The relative prevalences of paroxysmal, chronic, and recent onset AF were 22.1%, 51.4%, and 26.4%, respectively. Cardiac disorders, present in 534 patients (70.6%), included hypertension (39.4%), coronary artery disease (16.6%), and myocardial diseases (15.3%) as the most common. Rheumatic valvular disease represented a common cause in women (25. 0%) but not in men (8.0%). The paroxysmal group differed by a high percentage of palpitations (79.0%) and a low percentage of underlying heart disease (53.9%). With a mean follow-up of 8.6+/-3.7 months, 28 patients (3.7%) died, including 6 fatal cerebrovascular accidents. Among the 728 patients who survived, congestive heart failure occurred in 30 patients (4.1%), and embolic complications occurred in 13 patients (1.8%). In the paroxysmal AF group, 13 patients (8.0%) developed chronic AF and 51 (31.3%) had AF recurrences. At the time of follow-up, 53 patients (14.3%) from the chronic AF group and 108 patients (55.7%) from the recent onset AF group were in sinus rhythm. CONCLUSIONS: This large-scale study establishes the current demographic profile of out-of-hospital patients with AF and highlights some of the changes that have occurred in the past decades, including a particular shift in cardiac causes toward nonrheumatic AF. This study also demonstrates significant differences between various subsets of AF.

Adult↗

[Heart perforation following transvenous implantation of a cardiac pacemaker].

OBJECTIVES: We studied the incidence, clinical signs and severity of heart perforations occurring after transvenous pacemaker implantation. PATIENTS AND METHODS: A series of 16 consecutive cases of heart perforation observed in one cardiac pacing unit from 1989 to 1998 were reviewed. RESULTS: Heart perforation occurred after implantation in 9 cases; the verall incidence for all lead implantation was 0.57%. The ventricle was perforated in 6 cases, the atrium in 1, and an undetermined site in 2 cases. Active fixation was involved in 5 cases, passive fixation in 4. A bipolar lead was used in 7 cases and a unipolar lead in 2. Heart perforation occurred after prior external stimulation in 7 cases, including one case with tamponnade requiring emergency pericardial drainage after implantation. Repositioning the lead in the ventricle was sufficient in 6 cases and a thoracotomy for an atrial wound was performed in 1 case. Difficulties in right ventricular catheterism due to kyphoscoliosis in elderly subjects was found to be a risk factor. CONCLUSION: Heart perforation following transvenous pacemaker implantation is an exceptional complication with currently used material. Tamponnade is extremely rare. Besides verifying the mechanical performance of the leads, prevention requires a rigorous protocol for catheterism and wall fixation.

Age Factors↗

Cholesterol and omega-3 fatty acids inhibit Na, K-ATPase activity in human endothelial cells.

We have investigated the effects of cholesterol and omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexenoic acid (DHA) on Na, K-ATPase activity in human endothelial cells (HUVEC). Cultured HUVEC were incubated for 18 h with pure egg phosphatidylcholine (PC), or cholesterol-enriched liposomes (4 mg PC/ml). EPA and DHA alpha-tocopherol-acetate were emulsified with PC and incubated with HUVEC (10 mM). Na, K-ATPase and 5'-nucleotidase activities were determined using the coupled assay method on microsomal fractions obtained from cultured cells using non treated cells as control. Cholesterol enrichment significantly reduced both Na, K-ATPase and 5'-nucleotidase activities by a similar level (- 40%), whereas pure phospholipid liposomes inhibited this activity only by 22%. The dose-response curves of Na, K-ATPase activity were all biphasic assuming the presence of two independent sites exhibiting different affinities for ouabain of nM and microM respectively. The cholesterol induced inhibitory effect was greater for low affinity sites (-54%) as compared to that of the high affinity sites (-24%) whereas omega-3 fatty acids reduced the activity of both sites by 22%. Short term effects of EPA and DHA on Na, K-ATPase activity were determined by incubating microsomal fractions from untreated cells with various concentrations of free fatty acids (from 1 to 200 microM) for 20 min. Both EPA and DHA significantly reduced Na, K-ATPase activity but inhibition by EPA seems to be more effective than DHA. These results suggest that cholesterol and omega-3 fatty acids reduce Na, K-ATPase activity in HUVEC.

Cell Membrane↗

[Changes in homeostasis during surgical liver resection].

OBJECTIVES: To assess changes in haemostasis during liver resection and to discuss the indications for antifibrinolytic therapy. STUDY DESIGN: Open prospective study. PATIENTS: The study included 39 consecutive non-cirrhotic patients presenting for liver resection under portal triad clamping. METHOD: General anaesthesia was obtained with thiopentone, fentanyl, vecuronium and isoflurane. Transfusion scheme was standardized. Aprotinin (5,000 kIU.kg-1 BW) was administered in case of unexplained bleeding in the operative field. Coagulation pattern was assessed by routine tests and thrombelastrography before surgery, before portal triad clamping, 5 min after reperfusion and at completion of surgery. Patients requiring aprotinin intraoperatively were compared to others. RESULTS: In 32 patients no significant bleeding occurred. Their coagulation pattern was moderately changed and remained within the normal range. In seven patients severe bleeding occurred which was treated with aprotinin. Their coagulation tests were significantly modified, especially after reperfusion, associating an increase in aPTT, TT, FDP, DDim, r + k and a decreased platelet count. CONCLUSION: These changes were more in favour of a dilution coagulopathy or a DIC than hyperfibrinolysis. Therefore substitutive therapy with coagulation factors should be preferred to an antifibrinolytic agent. A systematic administration of the latter for liver resection in non-cirrhotic patients is debatable, considering the allergic risk (reoperation for cancer recurrence), thrombosis facilitation (pedicle clamping) and high cost.

Aged↗

Treatment of hepatitis C patients with normal aminotransferases levels.

An important subset of patients with chronic hepatitis C have normal ALT levels despite having detectable HCV RNA in serum. These patients are typically identified after donating blood and being found positive for antibody to HCV (anti-HCV). A strict definition of this patient population is needed, which should include the presence of anti-HCV, detectable HCV RNA by PCR and persistently normal ALT levels. These patients are usually asymptomatic, but on liver biopsy almost all have histologic evidence of chronic hepatitis. The histologic findings generally are mild, and cirrhosis is rare. The long-term outcome of this group of patients with chronic HCV infection is not known, but the prognosis is probably good. In small, uncontrolled trials of IFN-alpha in patients with normal ALT levels, end-of-treatment virologic responses occurred in 42% of patients, and sustained responses 6 to 12 months afterwards in 13% of patients. These rates of response are not very different from those reported in patients with elevated ALT levels. Importantly, in most studies, serum ALT levels became elevated during IFN therapy in approximately one half of patients, and levels remained elevated in some of these patients after therapy. These findings suggest that IFN-alpha therapy is not usually beneficial and may be harmful in chronic hepatitis C patients with normal ALT levels. Combination therapy with IFN and ribavirin has not been evaluated in this group of patients.

Alanine Transaminase↗

Internal low-energy cardioversion: a therapeutic option for restoring sinus rhythm in chronic atrial fibrillation after failure of external cardioversion.

AIMS: Conventional external cardioversion remains the technique of choice for restoration of sinus rhythm in patients with chronic atrial fibrillation (AF). Recent reports have suggested that internal low-energy cardioversion is efficient and safe in terminating AF in patients with failed external cardioversion. METHODS AND RESULTS: In 20 of 118 consecutive patients with spontaneous chronic AF (>7/days), who underwent low-energy cardioversion, one or more attempts at restoring sinus rhythm with external cardioversion had failed. Low-energy internal cardioversion was performed under light sedation. Shocks were delivered (using an external custom defibrillator) between two nonapolar catheters positioned in the right atrium (cathode) and in the coronary sinus (anode). Heart disease was present in 12 and absent in eight patients ('lone' atrial fibrillation). Atrial fibrillation was established for a period ranging from 12 days to 53 months. Low-energy internal cardioversion restored sinus rhythm in 15 of the 20 patients (75%) with a mean energy of 4.5+/-1.2 J, a mean conversion voltage of 355+/-53 V and a mean impedance of 63+/-8 ohms. No complications were observed. With a mean follow-up of 6+/-7 months, 11 patients (73%) were in stable sinus rhythm. CONCLUSIONS: This study provides evidence in support of low-energy internal cardioversion as a valuable therapeutic option in patients in whom conventional external cardioversion failed. This technique is safe and does not require general anaesthesia.

Adult↗

Dietary fish oil promotes positive inotropy of ouabain in the rat heart.

We tested the hypothesis that a fish oil (FO) diet promotes positive inotropy of ouabain without increased toxicity. For 2 mo, two groups of adult male rats were fed 1) a regular food diet supplemented with dietary long-chain polyunsaturated fatty acid from FO or 2) a regular food diet (control). The responsiveness to ouabain was evaluated for the two groups in Langendorff-perfused hearts, by (31)P nuclear magnetic resonance spectroscopy, and on purified membrane-bound Na-K-ATPase. The maximum positive inotropy achieved with ouabain was nearly two times higher in the FO than in the control group and was not associated with significant changes in energetics. Alteration of function and energetic metabolism and inhibition of Na-K-ATPase in response to 3 x 10(-4) M ouabain were delayed in the FO group. This study demonstrates that dietary FO, by a cardiac membrane incorporation of n-3 polyunsaturated fatty acid, promotes positive inotropy of ouabain without toxicity and changes in cardiac metabolism.

Animals↗

[Hereditary resistance to vitamin K antagonists. Apropos of a case].

Resistance to vitamin K antagonists is a rare phenomenon. In general, it is the result of poor patient compliance, malabsorption, a diet rich in vitamin K, or the use of enzyme inducers. Occasionally, the diagnosis of resistance is made when plasma levels are high. The authors report a case of hereditary resistance to vitamin K antagonists in a 43 year old man admitted for atrial fibrillation. The precise prevalence of this anomaly is unknown. However, the existence should be known to clinicians who often use this important family of drugs.

Adult↗

Relationship of plasminogen activator inhibitor-1 levels following thrombolytic therapy with rt-PA as compared to streptokinase and patency of infarct related coronary artery.

BACKGROUND: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. METHODS AND RESULTS: Fifty five consecutive patients with acute MI were randomized to streptokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5+/-1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p<0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p<0.002, p<0.04 and p<0.05 respectively). The same tendency was observed in the t-PA group without reaching significance. CONCLUSIONS: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

Biomarkers↗

[Implantable ventricular defibrillator. Systematic induction of ventricular arrhythmia is not useful except for implantation].

Checking the efficacy of a defibrillator after its implantation is current practice. This control usually entails induction of ventricular fibrillation (VF). The aim of this study was to assess the utility of this practice in patients with an endovascular system of electrodes. Implantation was acquired when a margin of security of 10 days or more had been obtained. During the postoperative test, the choice of energy was that which reduced VF at implantation. Of the 84 patients included in this study, 59 were implanted with an endovascular electrode system alone and the other 25 patients had endovascular electrodes associated with a subcutaneous patch electrode. The average time from implantation to the postoperative test was 31 +/- 12 days. Arrhythmia sensing was normal and reduction by the defibrillator was observed in all patients. The average energy of the electric shocks was not significantly different to that observed at implantation (18.6 +/- 3.6 J and 19.3 +/- 4.7 J). Fifty patients had antiarrhythmic drugs (amiodarone = 43) at implantation, and 32 at the time of the postoperative test (amiodarone = 17). This study showed that the postoperative test with induction of VF was normal in all patients. Therefore, the authors propose that follow-up should consist of consultation including interrogation of the defibrillator and a chest X-ray to check the position of the electrodes. If one of these tests is abnormal or if the perioperative threshold of defibrillation does not provide an adequate margin of safety, induction of a ventricular arrhythmia is necessary to check the function of the system.

Aged↗