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Biomedical subjects

P Lechat

Publications and source records attributed to P Lechat.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Adrenergic betablockers and heart failure].

Several studies have shown that beta-blockade could provide functional benefit in heart failure, suggesting a deleterious role for the compensatory sympathetic stimulation. Betablockers induced benefit could result from either antagonism of myocardial beta-adrenergic stimulation or, on the contrary a paradoxical increased cardiac beta-adrenergic responsiveness secondary to beta-adrenergic receptor up-regulation. Two recently completed large scale multicentric placebo controlled studies, the MDC trial with metoprolol and CIBIS with bisoprolol, have confirmed that beta-blockade could functionally improve patients with heart failure. The observed survival improvement in non-ischaemic patients was observed only in the CIBIS trial. This result requires confirmation by additional studies.

Adrenergic beta-Antagonists↗
PubMed1995

[Antihypertensive agents: specific molecules with therapeutic combinations].

The main goal of combination therapy in current antihypertensive treatment strategy is to achieve an additive or hopefully synergistic effect at a lower dose, hence with fewer side-effects. In reality, no one antihypertensive has a monolithic action profile: the therapeutic effect is the combined result of one or several individual effects, and the consequence of one of several adaptive mechanisms involved in physiological regulation. The action profiles of beta-adrenergic receptor blockers and converting enzyme inhibitors provide a good example of this complexity. The strategy for therapeutic use of an antihypertensive, including possible combination with another drug, thus depends on the level of impairment in the target structure (beta-adrenergic receptor, converting enzyme, calcium channel etc.), modulation of other target structures by the drug, and on the amplitude of counter-regulatory mechanisms that may be brought into play, whether directly or indirectly. The latter have greatest impact on the long-term outcome of antihypertensive treatment, in terms of myocardial hypertrophy, vascular remodeling, and atherosclerosis. Despite the multiple pharmacological and pharmacokinetic interactions leading to the development of increasingly sophisticated activity profiles and despite the use of increasingly focussed combination therapies, we must not forget that the role of many potential pharmacological targets still awaits investigation.

Adrenergic beta-Antagonists↗
PubMed1995

Evaluation of cryopreserved arteries as alternative small vessel prostheses.

Biologic or synthetic grafts have had limited success in small vessel applications. Studies were initiated to assess the potential use of cryopreserved (CP) arteries as coronary artery bypass conduits. Sheep carotid arteries (internal diameter: 4 mm; length: 10 cm) were cryopreserved in a nutrient media containing 10% DMSO and were stored in a nitrogen vapor at -150 degrees C. After thawing, histological, enzyme-histochemical and functional studies showed slight histological alterations, preservation of enzymal activities and an abolition of the contractile response. In a sheep model, arterial substitution of a 10 cm segment of carotid artery was realised by implantation of fresh autografts ( n = 4); fresh allografts (n = 9) and CP allografts (n = 9). After 3 months, all autografts were patent with slight histological alterations. Fresh and CP allografts showed similar modifications: patency rate was 7/9 in both groups. Intimal thickening with cell proliferation was seen in fresh (3/7) and CP (4/8) arteries; loss of smooth muscle medial cells was constant. Adventitia was always involved by a marked inflammatory reaction. One characteristic of CP allografts was the frequent presence of large dystrophic calcifications. In conclusion, morphologic and functional arterial changes occurred after freezing and thawing. In spite of vascular rejection, the patency rate of allografts after 3 months of implantation in arterial circulation remained high and does not seem influenced by cryopreservation.

Animals↗
PubMed1994

Viability of cryopreserved arterial wall: enzyme-histochemical and physiological markers.

Use of cryopreserved small-caliber arterial allografts for arterial bypass procedures has been suggested. In addition to immunological tolerance, long term in vivo success of these grafts may be dependent on the viability of arterial cells after cryopreservation. Metabolic and functional capabilities of arterial smooth muscle cells were evaluated by studying the enzyme histochemical expressions of sheep carotid arteries after various time of cryopreservation (7 days, 90 to 150 days) and their contractile responses after freezing. The results indicated that cryopreserved arteries exhibited 4 features: (a) the enzyme activities were globally maintained, (b) the spontaneous endogenous oxido-reduction (NitroBT test) was reduced, (c) contractile responses against KCl and norepinephrine were abolished, (d) metabolic status of frozen arteries was independent of the duration of cryopreservation. These data suggest that cryopreserved arterial muscle cells may be depleted in electron donors and/or energy-rich nucleotides substrates. This defect is present after short or long time of cryopreservation.

Animals↗
PubMed1993

Beta-adrenoceptor blockade potentiates acute exercise-induced release of atrial natriuretic peptide by increasing atrial diameter in normotensive healthy subjects.

The role of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E) and left atrial diameter at rest, during and after graded bicycle exercise has been studies in 8 healthy male subjects after single doses of placebo, tertatolol 5 mg (a non-selective beta-adrenoceptor blocker), prazosin 1 mg (an alpha 1-adrenoceptor antagonist) and their combination. Systolic and diastolic left atrial diameters were measured before, during and just after exercise by bidimensional echocardiography. Exercise caused an increase in plasma ANP, which was greater after tertatolol alone, and tertatolol plus prazosin, than after placebo or prazosin alone; the mean area under the plasma ANP concentration curve was increased by 35% after tertatolol alone, by 45% after tertatolol and prazosin compared to placebo, and by 82% and 94%, respectively when compared to prazosin alone. The rise in plasma ANP was more marked during the post-exercise period: 80% after tertatolol alone, 67% after tertatolol and prazosin compared to placebo, and 133% and 115%, respectively, compared to prazosin alone. The rise in plasma ANP was accompanied by an increase in both the systolic and diastolic atrial diameter, which was also significantly greater after tertatolol alone and the combination than placebo, or after prazosin alone. beta-Adrenoceptor blockade alone did not affect the plasma catecholamine concentrations, but the exercise-induced increase in plasma norepinephrine was significantly potentiated by prazosin and by prazosin plus tertatolol, and that of plasma epinephrine by the drug combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure.

The aim of this 3-month double-blind, placebo-controlled, multicenter trial was to evaluate the clinical efficacy and safety of perindopril, a new long-acting angiotensin-converting enzyme inhibitor in the second-line treatment of mild to moderate chronic congestive heart failure. After a run-in period of at least 14 days, 125 patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy were randomized to perindopril, 2 mg (n = 61), or placebo (n = 64), once daily. Assessment was at 2-week intervals for the first month and then monthly for the 2 following months. After 2 weeks, active treatment was increased to perindopril, 4 mg once daily, if systolic blood pressure was 100 mm Hg or greater. Apart from sex, the two groups were homogeneous before treatment. As shown by the end-point analysis, the increase in exercise time was greater with perindopril than with placebo for both the ergometric bicycle (+111 +/- 21 versus +16 +/- 20 seconds; p = 0.002) and the treadmill (+171 +/- 39 versus +36 +/- 42 seconds; p = 0.024). Compared with placebo, this increase in exercise tolerance with perindopril was accompanied by an improvement in New York Heart Association functional class (p = 0.009), overall heart failure severity score (p < 0.001), and cardiothoracic ratio (p = 0.05). Of the 12 withdrawals from the study, seven were attributed to adverse events, two in the perindopril group and five, including one death, in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Variations in plasma endothelin concentrations during coronary spasm.

A provocation test using methylergometrine was carried out in patients with a normal coronary angiogram. Patients exhibiting spasm (Group 1, n = 6) were compared with non-spasm patients (Group II, n = 6). The endothelin concentration was determined in all cases at 0800, 1100, 1400, 1600, 1900, 2100, 2300 and 0100 h. The provocation test was carried out at 1700 h and an additional determination was made during spasm if the test was positive. The two groups had similar clinical characteristics and did not differ in terms of risk factors. Apart from the value recorded during spasm, the endothelin plasma level was significantly higher in Group I. A time x measurement interaction was noted in both groups, with a higher endothelin level in the morning. The endothelin level increased significantly during spasm in Group I patients. The plasma concentration of endothelin appeared to be higher in the basal state and during spasm in patients exhibiting spastic angina.

Adult↗
PubMed1993

Tertatolol potentiates exercise-induced atrial natriuretic peptide release by increasing atrial diameter in healthy subjects.

To evaluate the contribution of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E), and left atrial diameter were measured at rest, during, and after graded upright standardised bicycle exercise in 8 healthy male subjects after single-dose administration of placebo, tertatolol (5 mg), prazosin (1 mg), or combination of tertatolol (5 mg) and prazosin (1 mg). Systolic and diastolic left atrial diameters were measured before, during, and just after exercise by bidimensional echocardiography. Exercise raised plasma ANP concentrations. This rise was greater on tertatolol alone and tertatolol and prazosin than on placebo or prazosin alone: mean area under the plasma ANP concentration curve increased by 35% on tertatolol alone, 45% on tertatolol and prazosin when compared with placebo (p < 0.01), and by 82 and 94%, respectively, when compared with prazosin alone (p < 0.01). The rise in plasma ANP was greater during the postexercise period: 80% for tertatolol alone, 67% for tertatolol and prazosin when compared with placebo (p < 0.01) and 133 and 115%, respectively, when compared with prazosin alone (p < 0.01). The rise in plasma ANP was accompanied by an increase in both systolic and diastolic atrial diameters which was significantly greater on tertatolol alone and on the tertatolol and prazosin combination than on placebo or prazosin alone (p < 0.001). Beta-blockade alone did not affect plasma catecholamine concentrations but exercise-induced increase in plasma NE was significantly potentiated by prazosin and the prazosin and tertatolol combination, and that of plasma E by the prazosin and tertatolol combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

[Heart rate and rhythm during flight in civil pilots undergoing aerobatics. A Holter study].

Variations in heart rate and arrhythmic risk were analysed during aerobatic manoeuvres carried out by 23 amateur pilots, affiliated to an air club or in the French national team, during training or competitive flight, by 43 Holter 2-channel continuous electrocardiographic recordings. The maximum, mean and minimum heart rates were raised before the flight started and were observed to attain or even exceed the age-predicted maximum heart rate during the manoeuvres. These values were independent of age, the pilot's experience, the acceleration forces, the duration of the flight or the aerobatic figures performed. On the other hand, the heart rate was much higher during competition than during training and pilot experience modified its variations, indicating that psychological stress played a major role in inducing the tachycardia. Aerobatic flying was only mildly arrhythmogenic, inducing some isolated extrasystoles and one short run of asymptomatic supraventricular tachycardia. Holter recording is a simple and economic method of monitoring aerobatic pilots and could help to improve training methods and our understanding of the physiological changes observed during flight.

Acceleration↗
PubMed1993

[Necrotic lesions, ischemia and reperfusion: effects of beta blockers].

The anti-ischemic properties of beta-blocking drugs have promoted their use during acute myocardial infarction. Beneficial effects are only observed with very early intravenous administration (less than 6 hours). Mortality is reduced by 14% and reinfarction by 18% during the 8 day post-infarction period. The incidence of ventricular fibrillation has been inconstantly decreased. Infarct size reduction is the most probable mechanism of beta-blockade induced protection. The thrombolytic-beta-blocker association seems to provide additional benefits compared with thrombolysis alone, but this remains to be demonstrated in large scale trials.

Adrenergic beta-Antagonists↗
PubMed1993

[Changes in plasma endothelin during coronary spasm].

The role of endothelin, a powerful vasoconstrictor, was studied in coronary spasm. A methylergonovine stress test was performed in patients with normal coronary angiography. Patients who developed spasm (Group I, n = 6) were compared with those who did not (Group II, n = 6). Plasma endothelin was measured at 8, 11 a.m., 2 p.m., 4, 7, 9, 11 p.m. and 1 a.m. The stress test was carried out at 17 hours and an additional endothelin measurement was performed during spasm in positive cases. The clinical characteristics of the two groups were comparable especially with regards to cardiovascular risk factors. Except for the value recorded during coronary spasm, the plasma endothelin levels were significantly higher in the group with coronary spasm. A time-dependent variation was observed in both groups with higher endothelin levels in the morning. In group I the plasma endothelin levels were higher under basal conditions and during spasm in patients with spastic angina.

Adult↗
PubMed1993

[Evaluation of a new cardiotonic agent on human isolated atrium].

The action of a phosphodiesterase inhibitor, RGW 29 38, was analysed experimentally. A preliminary study with guinea pig isolated heart, using Langhendorf's method, revealed a cardiotonic effect, though less than with isoprenaline and dobutamine, with which it was compared. The inotropic action of the compound was then studied using human isolated atrium. The model is described. It consisted of measurement by a strain gauge of the contractions obtained in a stimulated atrial fragment obtained during a surgical procedure. The following parameters were analysed, expressed as percentage increase in relation to baseline conditions: maximum tension developed, positive dP/dt and negative dP/dt. The effect of RGW (n = 6) was compared with that of isoprenaline (n = 7). RGW caused an increase in maximum tension of 195% +/- 91%, in positive dp/dt of 110% +/- 72% and in negative dp/dt of 168 +/- 54%. This increase was, however, less than that seen in the isoprenaline group. Thus RGW had a definite positive inotropic effect on guinea pig isolated heart and human isolated atrium, though less than that of the catecholamines with which it was compared. Isolated human atrium appears to be a useful study model, in particular for analysis of the inotropic action of drugs.

Animals↗
PubMed1992

Cardiomyopathy in Friedreich's ataxia: a Doppler-echocardiographic study.

Heart involvement is frequent in Friedreich's ataxia (FA), the most prevalent of the spino-cerebellar degenerative diseases, which is inherited with an autosomal recessive pattern. However, the pathophysiological link between cardiac and neurological disorders is not yet clearly established. We compared a group of 10 patients with FA to a control group (C) of 16 normal subjects, using Doppler-echocardiography. To see whether cardiac involvement was specific to FA, the data of patients with FA were also compared to those of patients with autosomal dominant olivo-ponto-cerebellar atrophia (OPCA), another spino-cerebellar degenerative disease. There was an increase in left ventricular mass index in FA (154 +/- 9 g.m-2 vs 99 +/- 7 g. m-2 in C, P < 0.001), systolic function was normal, the ejection fraction (EF) slope and E/A ratio were decreased (85 +/- 9 mm.s-1 vs 130 +/- 7 mm.s-1 in C, P < 0.001 and 1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.01, respectively), while the isovolumic relaxation period was increased (96 +/- 3 ms vs 92 +/- 2 ms in C, P < 0.01). Deceleration time and time-velocity integrals of A wave to total mitral flow were not modified. In OPCA only the E/A ratio was decreased (1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.05). These data show the presence of cardiomyopathy in FA with left ventricular hypertrophy and suggest the presence of diastolic function abnormalities. The cardiomyopathy seems specifically associated with FA and not to spino-cerebellar degenerative disease in general.

Adolescent↗
PubMed1992

Plasma calcitonin gene-related peptide decreases in chronic congestive heart failure.

To investigate the role of calcitonin gene-related peptide (CGRP) in cardiac failure, a sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in 37 normal subjects and 41 patients with heart failure (HF). The mean plasma levels of CGRP were 294.3 pg.ml-1 (SEM: 41.4) in normal subjects and 121.2 pg.ml-1 (SEM: 21.2) in HF patients. The significant decrease observed in HF patients suggests that CGRP is involved in the pathogenesis of heart failure via a direct effect or via modulation of sympathetic nervous activity.

Calcitonin Gene-Related Peptide↗
PubMed1992

[Non invasive evaluation of cardiovascular effects of nebivolol in patients with cardiac insufficiency].

The results of several studies, mostly without controls, have suggested that betablockers, administered at progressively increasing doses, may be beneficial in cardiac failure. Based on this hypothesis, betablockers with a peripheral vasodilator effect, such as Nebivolol, could be particularly valuable in this indication. A preliminary study of its tolerance, haemodynamic and neurohormonal effects was carried out with a noninvasive methodology in 12 patients with cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years), all of whom had Class III or IV symptoms according to the NYHA Classification. The protocol had 2 phases: the first was an open phase during which Nebivolol was administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the second phase, the patients were randomly separated into 2 groups, one to receive placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5 remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4 beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5 mg dosage. During the randomised phase, the heart rate remained stable in the Nebivolol group but increased to its initial value in the group given placebo. No aggravation of symptoms was observed in the Nebivolol group. No significant changes in cardiac output, parameters of cardiac loading or contractility could be demonstrated after 6 weeks' treatment. During submaximal exercise testing, plasma concentrations of catecholamines and atrial natriuretic factor tended to be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗