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Biomedical subjects

P Lechat

Publications and source records attributed to P Lechat.

At least 55 records · Page 3Linked to original sources
PubMed1997

Prognostic value of plasma endothelin-1 in patients with chronic heart failure.

AIMS: Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. METHODS AND RESULTS: Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001). CONCLUSION: Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Atrial Natriuretic Factor↗
PubMed1997

Hemodynamic and neurohormonal effects of flosequinan in patients with heart failure.

In a double-blind, placebo-controlled study, the central and peripheral hemodynamic effects of 100 mg oral flosequinan and the impact of this drug on neurohormonal activation were noninvasively evaluated in 18 patients with congestive heart failure, after the first administration and after 10 days of treatment. No significant hemodynamic and neurohormonal changes were observed after acute administration. After 10 days, flosequinan produced central and peripheral hemodynamic improvement characterized by an increase in left ventricular circumferential fiber shortening velocity (+12%), a decrease in total systemic resistance (-36%), and an increase in leg blood flow (+37%). No significant changes were observed in heart rate and arterial pressure in patients receiving flosequinan, though a slight increase in heart rate (+17%) was recorded. Despite these favorable hemodynamic effects, flosequinan significantly increased plasma norepinephrine (+38%) and plasma renin activity (+13%) after 10 days of treatment. Thus, the beneficial central and peripheral hemodynamic effects of flosequinan are accompanied by activation of the sympathetic and reninangiotensin systems. This might be related to the unfavorable effects of the drug on survival in patients with heart failure.

Adult↗
PubMed1996

Parasympathetic activity in Friedrich's ataxia.

We compared 19 patients with Friedreich's ataxia, a progressive hereditary neuromuscular disorder, with 19 healthy age-matched subjects. During nighttime, patients had shorter mean RR and decreased heart rate variability parameters related to parasympathetic activity than healthy subjects, whereas no difference occurred during daytime.

Adult↗
PubMed1996

Effects of bisoprolol on heart rate variability in heart failure.

Analysis of heart rate variability (HRV) provides a non-invasive index of autonomic nervous system activity. HRV has been shown to be reduced in heart failure. Preliminary data indicate that beta blockers improve clinical status in patients with heart failure, but HRV improvement remains to be demonstrated. Fifty-four patients from the randomized double-blind, placebo-controlled Cardiac Insufficiency Bisoprolol Study were included in the HRV study. The bisoprolol daily dose was 5 mg once daily. We assessed HRV during 24-hour Holter recordings before randomization and after 2 months of treatment. HRV as measured in the time domain by root-mean-square successive differences (rMSSD), the percentage of adjacent RR differences >50 ms (pNN50), and the SD of RR intervals (SDNN), and in the frequency domain by high-frequency (0.16 to 0.40 Hz) and low-frequency (0.04 to 0.15 Hz) power. Most patients were in New York Heart Association functional class III. The mean left ventricular ejection fraction was 27 +/- 7%, and heart failure was idiopathic or ischemic. After 2 months, the patients receiving bisoprolol had a reduced mean heart rate compared with that in placebo patients (p=0.0004). Bisoprolol increased 24-hour rMSSD (p=0.04) and 24-hour pNN50 (p=0.04), daytime SDNN (p=0.05), and daytime high-frequency power (p=0.03) power. Bisoprolol induced a significant increase in HRV parameters related to parasympathetic activity in heart failure. Increased vagal tone may contribute to the protective effect of beta blockers and may have prognostic implications.

Adrenergic beta-Antagonists↗
PubMed1996

Captopril does not acutely modulate plasma endothelin-1 concentration in human congestive heart failure.

Congestive heart failure (CHF) is a syndrome characterized by increased levels of angiotensin II (Ang II) and endothelin-1 (ET-1). In vitro, Ang II stimulates ET-1 release. The purpose of the study was to assess the effect of a single dose of an angiotensin-converting enzyme inhibitor (ACEI) captopril versus placebo on plasma endothelin concentration in human congestive heart failure. Captopril (25 mg, given orally) was compared with placebo in a group of 20 patients with systolic dysfunction in a double-blind randomized study. Plasma irET concentration was significantly increased in CHF patients compared with normal subjects (5.59 pg/ml +/- 0.35 vs. 3.58 pg/ml +/- 0.99, p < 0.0002). Despite the decrease in systolic blood pressure and the increase in plasma renin activity, suggesting a significant blockade of the renin-angiotensin system, no difference in plasma irET-1 was observed between captopril and placebo. Our results suggest that captopril does not acutely influence irET-1 plasma concentration in human CHF. These data do not support the hypothesis that the acute vasodilator effect of a single dose of 25 mg of captopril given daily orally involves modulation of the increased plasma concentration of endothelin observed in CHF.

Adult↗
PubMed1996

Persistent transient myocardial ischemia despite beta-adrenergic blockade predicts a higher risk of adverse cardiac events in patients with coronary artery disease.

OBJECTIVES: We evaluated the prevalence and prognostic significance of transient myocardial ischemia despite beta-adrenergic blockade in patients with coronary artery disease. BACKGROUND: Persistence of transient ischemia despite therapy may correspond to a subset of high risk patients with coronary disease. The impact of beta-blocker withdrawal in these patients remains unknown. METHODS: Patients (n = 313) with documented coronary artery disease and beta-blocker therapy, with (group I, n = 84) or without (group II, n = 229) transient ischemia on ambulatory electrocardiographic monitoring, were followed up during 21 +/- 9 months for cardiac events (death, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery and worsening angina). Occurrence of events was compared by log-rank test. RESULTS: The number of coronary stenoses did not differ significantly between groups I and II. Beta-blocker therapy was discontinued more frequently during follow-up in group II (25% vs. 14% in group I, p = 0.04). Cumulative percentage of death or myocardial infarction, or both, tended to be higher in group I a 30 months (17% vs. 5% in group II, p = 0.09). Coronary angioplasty and bypass surgery were significantly more frequent in group I (p = 0.01 and 0.0008, respectively). Transient ischemia was associated with a higher cumulative probability of adverse events (p = 0.004). The number of coronary stenoses, presence of transient ischemia and beta-blocker withdrawal were the only significant prognostic factors of cardiac events in the Cox model. In group I patients, the relative hazard of cardiac events was increased threefold when beta-blocker therapy was interrupted. CONCLUSIONS: These data suggest that 1) the occurrence of transient ischemia despite beta-blocker therapy identifies a subset of high risk patients with coronary artery disease, and 2) the interruption of beta-blocker therapy increases the risk of adverse cardiac events.

Adrenergic beta-Antagonists↗
PubMed1996

Effects of beta-blockade with bisoprolol on heart rate variability in advanced heart failure: analysis of scatterplots of R-R intervals at selected heart rates.

The effect of beta-blockade on heart-rate variability was assessed at different heart rates in 52 patients with heart failure included in the randomized, placebo-controlled, Cardiac Insufficiency Bisoprolol Study (CIBIS). Scatterplots of R-R intervals display beat-to-beat variability by plotting each R-R interval against the preceding interval. Scatterplot dispersion at different R-R intervals provides a measure of beat-to-beat heart-rate variability at different heart rates. A 24-hour Holter tape was performed at baseline and after 2 months of treatment with bisoprolol or matched placebo. Geometric measurements of scatterplots were used to determine beat-to-beat dispersion for different R-R intervals. Bisoprolol and placebo groups were well matched at base-line. After 2 months of treatment, bisoprolol significantly increased beat-to-beat variability at the longest R-R intervals (p < 0.05); however, there was no change in scatterplot dispersion at the shortest R-R intervals. This suggests that beta-blockade increases parasympathetic or decreases sympathetic tone or both in heart failure patients only at the slowest heart rates.

Adrenergic beta-Antagonists↗
PubMed1996

Acute and long-term dose-response study of quinapril on hormonal profile and tissue angiotensin-converting enzyme in Wistar rats.

Therapeutic response to angiotensin-converting enzyme (ACE) inhibitors was reported to be better related to tissular than to circulating levels of ACE inhibition, especially during chronic therapy. We studied the relations between plasma concentrations of angiotensin I (AI), plasma renin activity (PRA), angiotensin II (AII), and aldosterone (by radioimmunoassay, RIA) and levels of serum and tissue ACE activities during acute and chronic quinapril administration in rats. Forty-eight male Wistar rats received quinapril by gavage for either 1 day (n = 24) or 15 days (n = 24) at different doses (control, 0.1, 1, and 10 mg/kg/day; 6 rats at each dose). Plasma hormonal parameters, serum, and tissue (lung, heart, and aorta) ACE activities were measured 3 h after the last gavage. Significant dose-dependent inhibitions of serum and lung ACE during acute and chronic treatments were observed (p < 0.05). Degrees of serum and heart ACE inhibition (at 0.1 mg/kg/day) were significantly lower with chronic than with acute treatment (p < 0.05). Degree of inhibition in lung, which represents the main source of total ACE, was similar during acute and chronic treatments. Among plasma hormonal parameters, plasma AI was correlated to PRA and showed the best correlation with ACE inhibition. After logarithmic transformation, log AI was significantly correlated to ACE activity in lung during chronic treatment (r = -0.85, p < 0.05). This parameter may provide a useful index for ACE inhibitor dosage adjustment during chronic therapy.

Aldosterone↗
PubMed1996

Muscular blood flow response to submaximal leg exercise in normal subjects and in patients with heart failure.

Blood flow to working skeletal muscle is usually reduced during exercise in patients with congestive heart failure. An intrinsic impairment of skeletal muscle vasodilatory capacity has been suspected as a mechanism of this muscle underperfusion during maximal exercise, but its role during submaximal exercise remains unclear. Therefore, we studied by transcutaneous Doppler ultrasonography the arterial blood flow in the common femoral artery at rest and during a submaximal bicycle exercise in 12 normal subjects and in 30 patients with heart failure. Leg blood flow was lower in patients than in control subjects at rest [0.29 +/- 0.14 (SD) vs. 0.45 +/- 0.14 l/min, P < 0.01], at absolute powers and at the same relative power (2.17 +/- 1.06 vs. 4.39 +/- 1.4 l/min, P < 0.001). Because mean arterial pressure was maintained, leg vascular resistance was higher in patients than in control subjects at rest (407 +/- 187 vs. 247 +/- 71 mmHg.l-1.min, P < 0.01) and at the same relative power (73 +/- 49 vs. 31 +/- 13 mmHg.l-1.min, P < 0.01) but not at absolute powers. Although the magnitude of increase in leg blood flow corrected for power was similar in both groups (31 +/- 10 vs. 34 +/- 10 ml.min-1.W-1), the magnitude of decrease of leg vascular resistance corrected for power was higher in patients than in control subjects (5.9 +/- 3.3 vs. 1.9 +/- 0.94 mmHg.l-1.min.W-1, P < 0.001). These results suggest that the ability of skeletal muscle vascular resistance to decrease is not impaired and that intrinsic vascular abnormalities do not limit vasodilator response to submaximal exercise in patients with heart failure.

Adult↗
PubMed1996

Plasma levels and molecular forms of proatrial natriuretic peptides in healthy subjects and in patients with congestive heart failure.

A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1-30). Plasma concentrations of proANP(1-30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1-30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1-30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1-30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1-30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP.

Adult↗
PubMed1996

[Antithrombotic therapy of atrial fibrillation].

In comparison with the incidence of cerebrovascular accident in the general population, atrial fibrillation increases the risk by a factor of five. Although age is without doubt the main risk factor for cerebrovascular accidents in patients with permanent of paroxysmal non-valvular atrial fibrillation, other independent risk factors have been identified: a previous history of hypertension, cerebrovascular accident, heart failure or diabetes. These factors enable identification of a population at risk in which oral anticoagulation may be recommended with an excellent efficacy/risk ratio. Six large scale randomised controlled multicenter trials of primary prevention have been published with a total of over 2,800 patients with non-valvular atrial fibrillation. The combined results of these trials show that treatment with vitamin K antagonist (INR 2-3) leads to a significant reduction in the risk of an ischaemic cerebrovascular accident of 64% (95% CI [51-74]; p < 0.001) and in the risk of death from all causes of 28% (95% CI [12-47]; p = 0.038) with a slight increase in the risk of cerebral haemorrhage (+ 2.7% NS). Although the benefits of aspirin therapy are not as impressive (reduction of the risk of an ischaemic cerebrovascular accident of 22%; 95% CI [0-39]; p = 0.053), this alternative may be proposed in patients under 75 years of age without the previously mentioned risk factors. The value of combined aspirin-oral anticoagulant therapy, especially in high risk patients, has not yet been established and is under evaluation.

Adult↗
PubMed1995

[Reduction of atrial fibrillation. New concepts, new strategies].

Restoring sinus rhythm is patients with non-valvular atrial fibrillation has two objectives: restore haemodynamic performance and reduce the risk of thromboembolism. Whether the cardioversion is spontaneous or induced with drugs or electroshock, the process itself carries the risk of systemic embolism attributed to the transitory inactivity of the left atrium. Current practice of giving anticoagulants at least 4 weeks before electric cardioversion is a compromise between the embolic risk of cardioversion estimated at 0.4 to 0.8% and haemorrhagic complications related to low blood coagulability estimated at about 1% per year. The advent of transoesophageal echography has made it possible to study the atrium in detail in search of thrombi. The result has been a revolution in our concepts and therapeutic approach to atrial fibrillation and cardioversion. Recent studies have shown that "rapid cardioversion" associated with minimal 48-hour anticoagulation with heparin IV and transoesophageal echography to eliminate a thrombus in the atrium and/or the atrial appendage can be proposed without increasing the risk of embolism. Besides simplifying the therapeutic protocols (but at the cost of the semiinvasive nature of the transoesophageal echocardiography), this method also has the merit of restoring atrial function rapidly, particularly in cases of recent onset arrhythmia.

Atrial Fibrillation↗
PubMed1995

Effect of cold anoxia and cryopreservation on metabolic and contractile functions of human mammary artery.

The ability of human internal mammary artery smooth muscle cells to maintain histoenzymatic activity and contractile response after various times of cold anoxia prior to and following cryostorage was evaluated. The results showed that the enzyme histochemical status of human mammary arteries was largely unchanged after both cold anoxia and cryopreservation. Neither in fresh nor in cryopreserved mammary arteries did cold anoxia for up to 24 h change maximal contractile responses to potassium depolarization and norepinephrine. However, compared to unfrozen controls, the contractile responses were significantly reduced in cryopreserved mammary arteries. In conclusion, after cryopreservation of human mammary arteries, the enzyme activities were globally maintained, whereas the contractile responses were reduced. For up to 24 h after harvesting cold anoxia at 4 degrees C is well tolerated and allows preservation of metabolic and functional properties of these arteries.

Cell Hypoxia↗
PubMed1995

Effects of an endurance training programme on the passive and noradrenaline-activated compliances of rat aorta.

The effects of a 12-week endurance training programme (treadmill) upon the passive and the noradrenaline-activated properties of the aorta were studied in 15 trained and 24 sedentary rats. Aortic compliance was studied by measuring the length-tension curves of rings of the descending aorta without (passive properties) and with noradrenaline (noradrenaline activated) in a bubbling Krebs bath kept at a temperature of 37 degrees. The training effect on aortic volume compliance was studied by transforming the tension-length curves into a cross-sectional area-pressure curve according to Laplace's law. The noradrenaline responsiveness was studied by the dose-effect curve. The mechanical data were correlated with the results of a histomorphometric study which measured the aortic wall thickness and the percentages and amounts of elastic, connective and muscle components. Passive aortic compliance and volume compliance were higher in endurance-trained rats whose tunica media presented a lower percentage of collagen and a larger amount of elastic tissue. The dose-effect curve showed that the maximal aortic response to noradrenaline was stronger in trained rats but that the half maximal effective dose was not different. As a consequence, the length-tension curves of the noradrenaline fully activated aorta were similar in trained and sedentary rats except at the highest tensions where collagen is the main factor determining aortic stiffness. The increased noradrenaline response in trained rats was probably the result of the hypertrophy of the smooth muscle cells as maximal active strain (Newtons per square metre) was similar in trained and sedentary rats.

Animals↗
PubMed1995

Effects of amlodipine on transient myocardial ischaemia in patients with a severe coronary condition treated with a beta-blocker. Amlor-Holter Study Investigators.

The purpose of this trial was to study the additional anti-ischaemic effects of amlodipine in coronary patients with ambulant ischaemia despite beta-blocker therapy. Beta-blockers are the most effective drug therapy for reducing the frequency and duration of ambulatory ischaemic episodes. However, the therapeutic advantage of combined calcium antagonist-beta-blocker treatment remains questionable. Three hundred and thirteen patients with documented coronary artery disease, a positive exercise test within 6 months before entry and background beta-blocker therapy, were screened. Inclusion criteria (> or = 4 episodes of transient ST segment depression of > or = 1.0 mm and/or > or = 20 min of ischaemia) were demonstrated in a 48 h ECG during the placebo run-in period in 84 (25%) of the patients. Eighty-nine percent of the ischaemic episodes were silent. The eligible patients were then randomized in a 2-week, double-blind, parallel group study comparing placebo to amlodipine 10 mg daily added to the beta-blocker. The anti-ischaemic efficacy of the combination therapy was assessed by 48 h ECG monitoring and exercise tests. Compared to placebo, amlodipine did not significantly reduce either the frequency (3.7 +/- 4.3 vs 4 +/- 4.8 episodes in the amlodipine group) or the duration of ambulatory ischaemia (mean duration: 43.9 +/- 57.1 vs 39.6 +/- 65.7 min, total duration 3.1 +/- 6.7 vs 2.8 +/- 6.1 h). Exercise-induced ST segment depression tended to decrease with amlodipine (58% vs 73% in the placebo group) and the ischaemia-free workload capacity was increased (+1.7 stage vs 0.7 stage in the placebo group, P = 0.08). These results suggest that 2 weeks treatment with amlodipine may not provide any additional anti-ischaemic benefit in patients with ambulant ischaemia resistant to a beta-blocker therapy.

Adrenergic beta-Antagonists↗
PubMed1995

Evaluation of cardiac beta 1-adrenergic sensitivity with dobutamine in healthy volunteers.

1. Evaluation of cardiac beta 1-adrenergic sensitivity in heart failure should provide instructive therapeutic as well as prognostic information. We set up a non-invasive test in healthy volunteers to evaluate beta 1-adrenergic reactivity using dobutamine as a preferential agonist. 2. The range of i.v. bolus doses was 3.2 to 12.2 micrograms kg-1. The test was well tolerated. The parameters that were most sensitive and best correlated to dobutamine doses were systolic blood pressure and the rate-corrected electromechanical systole (QS2i). The reproducibility of the test over 48 h and over 1 month was satisfactory for most parameters, with a mean variation coefficient ranging from 9 to 26%, and was better for QS2i than for heart rate. 3. Slope of log dose-response for heart rate and QS2i was similar with dobutamine and with isoprenaline, corresponding to stimulation of the same type of beta-adrenergic receptors (beta 1-subtype). This result was obtained despite a higher vagal stimulation with dobutamine. We conclude that the left ventricular contractile response assessed by QS2i provided the best parameter for evaluation of beta 1-adrenergic cardiac effects either with dobutamine or with isoprenaline. 4. In heart failure patients such a dobutamine test should allow separation of altered contractility and beta-adrenergic desensitization, since alteration of inotropic response to dobutamine should depend on both altered contractile function and adrenergic desensitization but heart rate response should only depend on the latter phenomenon.

Adult↗