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Biomedical subjects

L Rochette

Publications and source records attributed to L Rochette.

At least 109 records · Page 6Linked to original sources
PubMed1995

Modification of vitamin E during ischemia-reperfusion in rat retina.

PURPOSE: To determine the variations of vitamin E in rat retinas after transient ischemia and reperfusion. METHODS: Male Wistar rats 11 to 12 weeks of age were used in all experiments. Ischemia was induced by ligation of the optic nerve and vessels, then reperfusion was obtained by removing the ligature. Retinas were dissected, and vitamin E was analyzed by a modified high-performance liquid chromatography assay. RESULTS: There was an insignificant rise in vitamin E during ischemia and a dramatic decrease after reperfusion. No changes were dependent on the period of ischemia (30, 60, or 90 minutes) or reperfusion (15 or 120 minutes). CONCLUSION: Vitamin E decreased only in the reperfused groups, demonstrating a depletion of defenses against free radical production occurring during reperfusion. Vitamin E changes may represent an indirect measure of lipoperoxidation during ischemia-reperfusion and, thus, a potential parameter to evaluate drugs in vitro.

Animals↗
PubMed1995

Temporal relationships between levels of circulating NO derivatives, vascular NO production and hyporeactivity to noradrenaline induced by endotoxin in rats.

OBJECTIVE: Lipopolysaccharide (LPS) induces early (within 1 h) and delayed (after several hours) impairment of vascular reactivity to catecholamines whose mechanisms are different, although they probably both involve nitric oxide (NO). Temporal and quantitative relationships between hyporeactivity to noradrenaline and NO production were investigated in a rat model of endotoxaemia allowing to clearly distinguish the two phases of hyporeactivity. METHODS: Anaesthetised rats were infused with LPS (14 mg kg-1 h-1) for 1 h. Pressure responses to noradrenaline (NA) and circulating NO derivatives (nitrosyl haemoglobin, NO2-, NO3-) were monitored for 5 h after the onset of infusion. Reactivity to NA and tissue cyclic GMP level were also assessed ex vivo, in aortic rings taken at different experimental times. RESULTS: LPS-induced early hyporeactivity to NA was associated with a moderate but significant increase in plasma NO3- level, without any significant change in concentration of the other circulating NO derivatives. Neither reactivity ex vivo nor cyclic GMP content were modified in aortae taken after 1 h of LPS infusion. By contrast, delayed hyporeactivity (5 h after the onset of LPS infusion) was associated with a large increase in all circulating NO derivatives (up to 2.5 fold), enhanced aortic cyclic GMP level and aortic hyporeactivity ex vivo. Pre-treatment of rats with NG-nitro-L-arginine methyl ester (1 mg kg-1 i.v.) entirely prevented early hyporeactivity and rise in NO3- concentration. In addition it attenuated in comparable proportion both delayed hyporeactivity to NA in vivo and circulating levels of NO derivatives. CONCLUSION: The results confirm the involvement of NO in the two phases of hyporeactivity to NA induced by LPS. They strongly support the view that a circulating factor is involved in triggering endothelial NO release during the early phase, whereas the delayed phase is associated with a high production of NO in vascular smooth muscle resulting from the induction of NO synthase.

Animals↗
PubMed1994

Benzoselenazolinone derivatives designed to be glutathione peroxidase mimetics feature inhibition of cyclooxygenase/5-lipoxygenase pathways and anti-inflammatory activity.

Two series of compounds, substituted benzoselenazolinones and their opened analogs, diselenides, were prepared. The diselenides were designed according to the available SAR about glutathione peroxidase mimics and were expected to have activity. An initial series of tests was performed in order to assess the glutathione peroxidase and antioxidant activity of the diselenides compared to their cyclized analogs. The diselenides were shown to be very potent (up to 3 times the activity of ebselen), whereas the benzoselenazolinones were inactive, thus confirming our hypothesis. A second series of tests was done to determine the anti-inflammatory potency of the two series. Both were found to be potent on cyclooxygenase and 5-lipoxygenase pathways (up to 95% inhibition at 10(-5) M). Some compounds were selective, and the variations in the activity allowed us to draft some structure-activity relationships. The most interesting compound of each series, 6-benzoylbenzoselenazolinone and bis[(2-amino-5-benzoyl)phenyl] diselenide, was tested in vivo on the rat foot edema induced with different phlogistic agents and was shown to have some anti-inflammatory properties.

Animals↗
PubMed1994

Effects of ATP-dependent K+ channel modulators on an ischemia-reperfusion rabbit isolated heart model with programmed electrical stimulation.

The effects of glibenclamide and BRL-38227 were studied in isolated rabbit hearts subjected to ischemia and programmed electrical stimulation. Coronary artery occlusion over 24 min decreased the ventricular effective refractory period in the ischemic zone. BRL-38227 (0.1 microM) showed significant coronary vasodilator effects, but failed to modify the ventricular effective refractory period under these conditions. A higher concentration (5 microM) of BRL-38227 potentiated the ischemia induced ventricular effective refractory period shortening effects. Glibenclamide (0.1 and 1 microM) delayed the onset of the ischemia-induced ventricular effective refractory period shortening. Glibenclamide (1 microM) inhibited the potentiated ventricular effective refractory period shortening effects of BRL-38227 (5 microM) during ischemia, but failed to antagonise the coronary vasodilator effects of BRL-38227 (5 microM). A higher incidence of ventricular fibrillation was inducible when an extra beat was applied in the ischemic zone through programmed electrical stimulation. The incidence of programmed electrical stimulation induced ventricular fibrillation was increased by BRL-38227 (5 microM) and antagonised by glibenclamide (1 microM). The results suggest that high concentrations of KATP-activators can accentuate ischemia-induced decreases in refractory period and increase the susceptibility of hearts to ventricular fibrillation when an extra beat is applied to the ischemic myocardium. These effects did not occur at lower coronary vasodilating concentrations of BRL-38227.

Adenosine Triphosphate↗
PubMed1994

Plasma lipid peroxidation in critically ill patients: importance of mechanical ventilation.

Oxygen free radicals may be implicated in the pathogenesis of both ischemia-reperfusion damage and in circulatory shock. The attack on the cell membrane by free radicals leads to lipid peroxidation, which can be assessed by the plasma malondialdehyde (MDA) level. The aim of this study was to determine the importance of lipid peroxidation in critically ill patients. The MDA level was measured by the thiobarbituric acid test. Nineteen patients at an early stage of circulatory shock, 11 patients in the weaning period of ventilation, 9 gastro-enterological patients without cardio-circulatory distress or sepsis, and 9 healthy volunteers were studied. The MDA level was higher in critically ill patients than in control subjects (61% in patients with shock and 40% in patients on mechanical ventilation). No correlation was found between the MDA level and the outcome: multiple organ failure or acute respiratory distress syndrome. This proposal leads to the question of systematic antioxidant therapy in intensive care patients.

Adolescent↗
PubMed1994

Prolongation by captopril of action potential duration in the normal and hypertrophied rat ventricle: direct action or inhibition of the local angiotensin converting enzyme?

OBJECTIVE: The aims were: (1) to study the acute effects of captopril on the action potential characteristics of ventricular fibres from the normal rat, (2) to compare the effects of captopril with those of perindoprilat, a non-thiol angiotensin I converting enzyme (ACE) inhibitor, (3) to determine the electrophysiological properties of the peptide substrates of converting enzyme, bradykinin and angiotensin I, and (4) to investigate whether the effects of captopril occurring in the healthy heart also occur in two models of ventricular hypertrophy. METHODS: Action potentials were recorded with the standard glass microelectrode technique in right ventricular preparations excised from rat hearts and superfused under baseline conditions and with drug containing or peptide containing Tyrode solution. Ventricular hypertrophy was induced in response to hypertension (unilaterally nephrectomised, DOCA-salt model) or 4 week old left ventricular infarction. RESULTS: In preparations from normal rat hearts, captopril increased action potential duration in a concentration dependent fashion [EC50 = 3.5 x 10(-8) M; maximum effect = 44(SEM 5.1)% prolongation at 10(-5) M for action potential duration at 90% repolarisation, APD90]. Perindoprilat similarly caused a dose dependent increase in action potential duration, but with 100 times greater potency [EC50 = 3.1 x 10(-10) M; maximum effect = 71(11)% prolongation at 10(-5) M for APD90]. SQ 14,534, a stereoisomer of captopril with one hundredth the ACE inhibitor potency, had no significant effect on action potential duration at 10(-5) M. Angiotensin I and bradykinin caused concentration dependent prolongation of action potential, but angiotensin II (10(-6) M) had no effect. Captopril (10(-5) M) had no significant effect in the hypertrophied right ventricle from DOCA-salt hypertensive rats, but significantly increased APD90 [39(4.9)%] in right ventricular preparations from rats with 4 week old anterior left ventricular infarction. CONCLUSIONS: In the rat, captopril prolongs action potential duration, an effect possibly due to local accumulation of bradykinin and angiotensin I.

Action Potentials↗
PubMed1994

Early incidence of adriamycin treatment on cardiac parameters in the rat.

To evaluate the early effect of low doses of adriamycin (ADR) on cardiac parameters, male Wistar rats were injected with ADR (1 mg.kg-1.day-1) or saline for 10 days. Seven days later, T1 and T2 relaxation times were determined in left ventricular (LV) free wall, septum, and thigh muscle samples. In another experiment, performed on isolated working hearts of rats pretreated with ADR, LV performance was determined along with an index of myocardial lipid peroxidation in this tissue. Lipid peroxidation was enhanced (p < 0.05). This change was not associated with a reduced LV performance, since both aortic and cardiac flows measured in working heart preparations were similar between control and treated rats. However, the coronary flow was significantly reduced (control group, 21 +/- 1 mL.min-1.g-1, ADR group, 15 +/- 1 mL.min-1.g-1; p < 0.001). T1 increased in the LV free wall (665 +/- 3 to 696 +/- 5 ms, p < 0.001) and in the septum (657 +/- 3 to 696 +/- 5 ms, p < 0.01), while T2 increased only in the LV free wall (50.8 +/- 0.9 to 53.1 +/- 0.6 ms, p < 0.05). Myocardial water content was also significantly increased. No modification was observed in the thigh muscle samples. Thus, modifications of T1 and T2 relaxation times following ADR treatment are associated with biochemical changes implicating lipid peroxidation. These changes in relaxation times appeared earlier than hemodynamic deterioration and could provide a basis for the application of proton nuclear magnetic resonance imaging in the early detection of cardiac ADR toxicity.

Animals↗
PubMed1993

Rat vitamin E status and heart lipid peroxidation: effect of dietary alpha-linolenic acid and marine n-3 fatty acids.

Three groups of sixteen male rats each were fed semi-purified diets containing 15% by weight of lipid for a period of 4 wk. The diets contained the same amount of polyunsaturated fatty acids (PUFA) (20% of total fatty acids) and saturated fatty acids (19% of total fatty acids). Dietary PUFA were represented exclusively by linoleic acid (18:2 diet), or 10% linoleic acid and 10% linolenic acid (18:3 diet), or 10% linoleic acid and 10% long-chain n-3 fatty acids (LCn-3 diet). The overall amount of vitamin E was similar in the three diets, i.e., 140, 133 and 129 mg/kg diet, respectively. Following appropriate extraction, tocopherol levels in heart, liver, brain, adipose tissue (AT) and plasma were measured by high-performance liquid chromatography. The level of vitamin E in the heart decreased with n-3 PUFA diets, most markedly with LCn-3 PUFA. Liver and AT vitamin E contents also decreased with n-3 PUFA diets when expressed as micrograms/mg total lipids and micrograms/mg phospholipids, respectively. Total plasma vitamin E was lower in rats fed the LCn-3 diet, but there was no significant difference when expressed as microgram/mg total lipids. Brain vitamin E was not affected by the various diets. In vitro cardiac lipid peroxidation was quantified by the thiobarbituric acid reactive substances (TBARS) test. Heart homogenates were incubated at 37 degrees C for 15 and 30 min in both the absence (uninduced) or presence (induced) of a free radical generating system (1 mM xanthine, 0.1 IU per mL xanthine oxidase, 0.2 mM/0.4 mM Fe/ethylenediaminetetraacetic acid). TBARS release was time-independent but significantly higher when LCn-3 fatty acids were fed to rats in either the uninduced or induced system. The study demonstrated that n-3 PUFA diets can influence vitamin E status of rats even in short-term experiments and can change the susceptibility of the heart to in vitro lipid peroxidation.

Adipose Tissue↗
PubMed1993

An alpha-tocopherol analogue with antioxidant activity improves myocardial function during ischemia reperfusion in isolated working rat hearts.

Recently, it has been reported that alpha-tocopherol analogues reduce infarct size in vivo in the rat and improve contractility upon reperfusion following global ischemia in isolated rat hearts. In the present study, we have thus investigated the effects of the hydrophilic alpha-tocopherol analogue MDL 74366 on nonenzymatic lipid peroxidation using a tissue homogenate method and reperfusion-induced arrhythmias following a local ischemia in isolated working rat hearts. Lipoperoxide (LPO) production was inhibited in a concentration-dependent manner in spontaneous as well as in induced peroxidations. The concentration resulting in a 50% inhibition (IC50) was around 2 microM. MDL 74366 treatment had no significant effect on baseline heart rate and cardiac output values. However, MDL 74366 decreased the incidence of reperfusion arrhythmias (ventricular tachycardia, VT; ventricular fibrillation, VF). The coincidence observed between the protective effect of MDL 74366 against tissue LPO formation and the preventive effect of this alpha-tocopherol analogue in the heart during the ischemia-reperfusion sequence confirms that vitamin E has beneficial effects against induced oxidative damage.

Animals↗
PubMed1993

Absence of relationship between antiarrhythmic effects of antidepressant drugs and lipid peroxidation.

Tricyclic antidepressant drugs may affect the cardiovascular system, principally in patients with preexisting cardiac disease. The present study was undertaken to compare the effects of amitriptyline and mianserin with those of tianeptine, an atypical tricyclic antidepressant drug, in rat isolated working heart subjected to a local myocardial ischemia. Coronary, aortic and cardiac flows, and heart rate remained stable during the whole preischemic period in control hearts. Ligation of the left main coronary artery induced a 50% decrease in coronary, aortic and cardiac flow without any change in heart rate. Reperfusion was characterized by the occurrence of ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) and by a marked reduction in cardiodynamic parameters. Amitriptyline (1 and 10 mumol/l) and mianserin (1 and 10 mumol/l) exhibited an antiarrhythmic activity against reperfusion arrhythmias. Tianeptine (1 and 10 mumol/l) was not able to reduce the incidence of reperfusion arrhythmias. Although tianeptine did not change heart rate, mianserin and amitriptyline induced a bradycardia. Mianserin and amitriptyline improved the cardiac recovery of cardiac function during reperfusion. The cardiodynamic parameters (coronary, aortic and cardiac flows) were not altered by tianeptine during the preischemic period. Furthermore, these parameters were similar to those observed in the control group both during ischemia and reperfusion. The beneficial effects of amitriptyline and mianserin observed in the setting of myocardial reperfusion were not associated with a reduced lipoperoxidation investigated by using an in vitro model in the presence or absence of a free-radical-generating system. The results of the present study indicate that the pronounced antiarrhythmic activities of mianserin and amitriptyline cannot be explained by an antiperoxidative action of these drugs.

Amitriptyline↗
PubMed1993

[From ischemia to reperfusion lesions].

It is well established that early reperfusion of ischemic myocardium limits or even prevents necrosis. However, sometimes restitution of coronary flow to the ischemic myocardium may precipitate a sequence of events that would have occurred either later or not at all. To prove the existence of reperfusion-induced injury, it is necessary to show that cells, potentially viable before reperfusion, are killed by the onset of reperfusion. The consequences of reperfusion are reperfusion-induced arrhythmias, myocardial stunning, accelerated necrosis and lethal reperfusion injury. The two main theories explaining the development of reperfusion injury are formation of free radicals and cellular calcium overload. Free radicals produced during early reperfusion may cause oxidant stress to membrane lipids and proteins associated with a potassium loss and a temporary cytosolic calcium overload. Results of experiments with free radical scavengers are contradictory for unknown reasons suggesting that reperfusion injury is a complex event innowing endothelial damage, leukocyte-plugged vessels, microvascular damage and production of heat-shock proteins.

Arrhythmias, Cardiac↗
PubMed1993

[Identification and evaluation of free radicals in the sequence cardiac ischemia-reperfusion].

The role of free radicals (FR) has been suggested in the development of ischaemia-induced myocardial reperfusion. When the equilibrium between the cellular sources and defense system is disturbed, FR may react with cellular components and produce a number of lesions. In general, the action of FR is shown indirectly by studying the effects of substances interfering with the production or the elimination of FR or of systems which produce FR on the physiopathological consequences of ischaemia and reperfusion. A physico-chemical technique, Electronic Paramagnetic Resonance (EPR) has been used in biology. The high reactivity and the very short life span of several types of FR pose methodological problems. A "stabilisation" of FR may be obtained by spin-trapping, a technique which consists of adding a diamagnetic substance to the reaction which forms covalent bonds with FR and forms a stable, detectable radical product. This technique has enabled identification and evaluation of FR liberated in the perfusion fluid of isolated perfused rat hearts and to determine the importance of the different mechanisms of production.

Animals↗
PubMed1992

Interpretation of epicardial mapping by means of computer simulations: applications to calcium, lidocaine and to BRL 34915.

The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' construction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit can develop. The experimental study shows that BRL 34915 has both arrhythmogenic and antiarrhythmic effects. A detailed electrophysiological analysis has shown that drug infusion act on normal cardiac cells by decreasing the relative and absolute refractory period. BRL 34915 action is simulated by a decrease in the refractory period showing that the time frequency of the reentrant activity is increased and that the spatial size where the reentry is developing is becoming smaller. These two effects are arrhythmogenic, the simulated data being so in good agreement with the experimental ones.

Animals↗
PubMed1992

[Free radicals, lipid peroxidation and muscular ischemia].

The role of oxygen free radicals in ischemia and reperfusion injury of skeletal muscle has not been well defined, partly because of the relative resistance of this tissue to normothermic ischemia. Under normal conditions small quantities of oxygen free radicals are produced but they are quenched by intracellular free radical scavenging enzymes (superoxide dismutase, catalase and glutathione peroxidase) or alpha-tocopherol. The increase in malondialdehyde suggests increased lipid peroxidation initiated by free radical reactions. Lipid peroxidation is potentially a very damaging process to the organized structure and function of membranes. The results of recent studies indicate that: a) oxygen free-radicals mediates, at least in part, the increased microvascular permeability produced by reoxygenation, b) free radical scavengers can reduce skeletal muscle necrosis occurring after prolonged ischemia. Additional evidence support the hypothesis of the interrelationship between ischemic tissue and inflammatory cells. So capillary plugging by granulocytes and oxygen free radical formation may contribute to the ischemic injury.

Animals↗
PubMed1992

Relations between reperfusion arrhythmias and myocardial norepinephrine and accumulation of calcium in the rat.

The relation between myocardial norepinephrine and reperfusion arrhythmias was examined in isolated rat hearts. The influence of pre-treatment with reserpine on the incidence of reperfusion arrhythmias and on the accumulation of calcium in the myocardium during ischemia and reperfusion was also studied. Ischemia was induced by ligation of the coronary artery and, in some experiments, the cardiac stores of norepinephrine were labeled with 3H-norepinephrine. Reperfusion after an ischemic period of 10 or 15 minutes induced a marked release of radioactivity and reperfusion arrhythmias. The radioactivity liberated after ischemia appeared to have been trapped during ischemia and washed out during reperfusion. Pre-treatment of the hearts with 0.1 mg/kg reserpine 24 hours before the experiment protected against reperfusion arrhythmias and significantly reduced the accumulation of calcium during reperfusion. The results confirm that the nature of reperfusion arrhythmias is highly dependent upon the duration of the ischemic period and sympathetic activity.

Animals↗
PubMed1991

The descriptive epidemiology of hysterectomy, Province of Quebec, 1981-1988.

This study reports the descriptive epidemiology of hysterectomy in the Province of Quebec, Canada, from 1981 to 1988. Data on hysterectomies (n = 150,849) among women 15 years and older were obtained from MED-ECHO, a computerized database of hospital discharge summaries. Hysterectomy rates were established, with denominators consisting of the estimated female populations with a uterus. From 1981 to 1988, the age-adjusted rate for hysterectomy declined from 100.4 to 67.4 per 10,000 women with a uterus. Curves representing age-specific rates of hysterectomy revealed a consistent bimodal pattern over time, a first peak occurring in women aged 40 to 44 years, and a second in women aged 65 to 69. Hysterectomy rates for elective conditions such as leiomyoma, endometriosis, disorders of menstruation, and prolapse decreased consistently over time. The proportion of women who had a hysterectomy and simultaneous bilateral oophorectomy declined from 35% in 1981 to 30% in 1988. Despite the substantial decline in the frequency of hysterectomy over the 8-year period, at rates prevailing in 1988, three of ten women would have had a hysterectomy by the age of 60.

Adolescent↗