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Biomedical subjects

I Macquin-Mavier

Publications and source records attributed to I Macquin-Mavier.

At least 19 recordsLinked to original sources
PubMed2001

Altered baroreflex gain during voluntary breathing in chronic heart failure.

BACKGROUND: We assessed the behavior of the baroreflex (BR) gain in chronic heart failure (CHF) patients using the spectral analysis method during application of a forcing stimulus, i.e. respiration. METHODS: Simultaneous RR interval and arterial pressure fluctuation recordings were obtained during two random-order periods of voluntary paced-breathing (0.15 Hz and 0.25 Hz) in seven patients with moderate CHF (NYHA class II/III; EF, 30+/-9%; peak VO(2), 18+/-5 ml kg(-1) min(-1)) and six age-matched controls. BR gain was assessed in the time (sequential method) and frequency (cross-spectral gain in the low and high frequency) domains. RESULTS: Slower breathing was associated with a BR gain decrease in CHF patients whereas a BR gain increase was evidenced in controls (BR gain: 6+/-5 ms mmHg(-1) at 0.25 Hz vs. 4+/-3 ms mmHg(-1) at 0.15 Hz, P<0.05 in CHF; BR gain: 12+/-7 ms mmHg(-1) at 0.25 Hz vs. 15+/-7 ms mmHg(-1) at 0.15 Hz, P<0.05 in controls). CONCLUSIONS: Voluntary breathing, which involves cortical centers in the brain, had major effects on cardiovascular system controller gain in CHF patients, indicating an impairment of the central neural regulation of the autonomic outflow.

Adult↗
PubMed2001

Simultaneous analysis of heart rate variability and myocardial contractility during head-up tilt in patients with vasovagal syncope.

INTRODUCTION: The aim of this study was to evaluate simultaneously cardiac autonomic activity, through heart rate variability (HRV) analysis, and cardiac inotropic changes during head-up tilt (HUT) in patients with recurrent vasovagal syncope. METHODS AND RESULTS: Twelve subjects implanted with a permanent dual-chamber pacemaker for recurrent vasovagal syncope characterized by marked bradycardia were studied. The tip of the right ventricular electrode was equipped with a sensor that measured peak endocardial acceleration (PEA) as an index of myocardial contractility. RR interval and PEA signals were acquired simultaneously and processed in the time and frequency (low frequencies [LF] and high frequencies [HF] of RR signal) domain during early HUT (T1), late HUT, or before syncope (T2). In the six subjects with positive HUT: (1) Abnormal heart rate oscillations were evidenced at T1 and discriminated this group from the negative group (LF/HF decreased by 46% from supine to T1, but increased by 55% in the negative group; P < 0.01 positive vs negative HUT). (2) Gradual diminution of the HF component was associated with an increase in PEA index during HUT with a correlation between PEA/RR interval (R = -0.8, P < 0.001), PEA/HF components (R = -0.6, P < 0.05). (3) Sympathetic stimulation responsible for changes in both HRV and PEA parameters occurred immediately before the faint (LF/LF+HF: 0.6 +/- 0.2 to 0.8 +/- 0.09; P < 0.05 T2 vs T1; PEA: 0.62 +/- 0.10G to 0.83 +/- 0.22G; P < 0.01 T2 vs T1). CONCLUSION: Our findings showed that a homogeneous subgroup of patients with recurrent vasovagal syncope and positive HUT exhibited abnormal cardiac autonomic and inotropic responses to an orthostatic stimulus. Continuous changes over time of HRV and PEA parameters highlight the dynamic behavior of the mechanisms leading to syncope.

Adult↗
PubMed1999

Low blood cholesterol and low platelet serotonin levels in violent suicide attempters.

AIM OF THE STUDY: This study investigated the possible connection between serum cholesterol levels and platelet serotonin (5-HT) content in violent suicide attempters and matched controls. METHODS: Blood samples for cholesterol and platelet 5-HT levels were obtained from 17 drug-free patients within 3 days after the suicide attempt. RESULTS: Serum cholesterol and platelet 5-HT levels in the suicide attempters were significantly lower than in the controls; however, we did not find any significant correlation between these two variables. Indeed, three clinical dimensions are present in this patient group: suicidality, violence, and impulsiveness. Because we did not find a difference in cholesterol and platelet 5-HT levels between impulsive and nonimpulsive patients, these two indexes may more reflect the dimension of suicidality and/or violence. CONCLUSIONS: Further investigation is necessary to study the dependence of these two peripheral abnormalities within the context of violent suicidal behavior.

Adult↗
PubMed1997

Repeatability of spectral components of short-term blood pressure and heart rate variability during acute sympathetic activation in healthy young male subjects.

1. Changes in the low-frequency (LF) components of blood pressure and heart rate variability and in the ratio of LF to high-frequency (HF) components of heart rate variability (LF/HF ratio) are used to assess acute changes in sympathetic control of blood pressure or heart rate and in sympathovagal balance that occur in response to physiological or pharmacological stimuli. Before these spectral indexes can be used to assess the effects of drug therapy or other clinical interventions on reflex sympathetic activity, their repeatability must be evaluated. 2. Intra-observer repeatability was studied by analysing changes in the LF components (expressed as absolute or normalized units) of cardiovascular variability and in the LF/HF ratio during sympathetic activation induced by nitroglycerin infusion (n = 10 subjects) or 60 degrees head-up tilt (n = 13 subjects) repeated on two occasions, 2 days and 1 week apart respectively, in healthy young male volunteers. Repeatability was estimated as recommended by Bland and Altman. 3. Bland and Altman's plots of the repeatability of changes in the LF components and LF/HF ratio showed that measurements were sufficiently repeatable to be used over periods of time of up to 1 week in clinical studies. 4. The sample-size tables derived from our results show that expression of spectral components as normalized units, and use of a cross-over design, minimize the number of subjects to be included in clinical studies conducted using similar designs and LF component changes as endpoints.

Adult↗
PubMed1996

Aerosolized tachykinin antagonists inhibit pentamidine-induce bronchoconstriction in guinea pigs.

To investigate the role of tachykinins in pentamidine-induced bronchoconstriction and airway microvascular leakage in the guinea pig, we examined the effects on bronchoconstriction and microvascular leakage of the nonpeptide antagonists of NK1 and NK2 tachykinin-receptors, respectively, CP-96,345 and SR 48968. Respiratory system resistance was measured by the occlusion method in anaesthetized, tracheotomized and mechanically ventilated guinea pigs. Airway microvascular permeability was evaluated by measuring the quantity of Evans blue dye in the trachea and main bronchi. Aerosolized CP-96,345 or SR 48968 partially abolished pentamidine-induced bronchoconstriction (at 5 to 30 mg/mL pentamidine; 60 breaths) whereas the combination of the two prevented it. In contrast, CP-96,345 and SR 48968 did not prevent the increase in airway microvascular permeability induced by pentamidine (50 mg/mL; 90 breaths) whether they were administered separately or together, by aerosol or intravenously. These results demonstrate that in the guinea pig, pentamidine-induced bronchoconstriction is mediated through both NK1 and NK2 tachykinin-receptor activation and that when directly administered into the airways, tachykinin antagonists effectively prevent pentamidine-induced bronchoconstriction.

Aerosols↗
PubMed1996

Airway epithelial damage induced by sulfur mustard in guinea pigs, effects of glucocorticoids.

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a significant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclusion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observations and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.

Animals↗
PubMed1996

Oxidant-antioxidant balance in alveolar macrophages from newborn rats.

An oxidant-antioxidant imbalance in neonatal alveolar macrophages (AMs) may contribute to the increased susceptibility to lung injury described in the neonatal period. We therefore evaluated oxygen radical production by rat AMs at various postnatal ages, and measured in parallel cellular antioxidant enzyme activities. AMs were obtained by bronchoalveolar lavage from rats aged < 24 h, 21 days and 5 weeks, and results were compared to those obtained with adult rat AMs. Intracellular production of oxygen radical species, estimated fluorometrically using 2',5'-dichlorofluorescein diacetate as the substrate, was significantly reduced in neonates as compared with adults, both in the presence and in the absence of cell stimulation with phorbol myristate acetate (PMA) or opsonized zymosan. A similar pattern was observed for the extracellular release of oxygen radical species, evaluated by lucigenin-enhanced chemiluminescence (CL) or peroxidase-catalysed CL oxidation of luminol: peak CL values measured after cell stimulation with PMA or opsonized zymosan remained significantly lower for AMs from newborn rats than for AMs from adults. By contrast, high values for antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) in AMs were demonstrated in newborns as compared to adults. We conclude that high antioxidant activity in rat AMs after birth may be at least partly responsible for the low production of oxygen metabolites observed during the same period.

Aging↗
PubMed1995

Tachykinins induce gelatinase production by guinea pig alveolar macrophages: involvement of NK2 receptors.

To determine whether tachykinins induce gelatinase production by guinea pig alveolar macrophages (AM), and to characterize the mechanism involved, we incubated AM with substance P (SP), neurokinin A (NKA), or the NH2-terminal fragment of SP, SP(1-7). The effects of increasing concentrations of selective NK1 and NK2 agonists on tachykinin-induced gelatinase production were also evaluated, as were the effects of a selective NK2 antagonist. Gelatinase activity in conditioned culture media (CCM) was assessed by zymography and quantified by image analysis. SP increased 92-kDa gelatinase activity in CCM of AM in a concentration-dependent manner, with a maximum increase at 10(-4) M. NKA, the NH2-terminal fragment of SP, and an NK1-selective agonist had no effect. In contrast, a selective NK2 agonist induced a concentration-dependent increase in gelatinase activity. The increase in this activity induced by SP and the selective NK2 agonist was inhibited by a selective NK2 antagonist. We conclude that SP induces gelatinase production by AM through NK2 receptor activation. The release of gelatinase may constitute one mechanism through which SP contributes to the epithelial lesions observed in bronchial hyperreactivity and asthma.

Animals↗
PubMed1995

Increased 92 kD gelatinase activity from alveolar macrophages in newborn rats.

The functional immaturity of neonatal alveolar macrophages (AM) may contribute to the increased susceptibility of neonates to lung injury. Because the secretion of proteinases by neonatal AMs may be involved in normal postnatal lung development and in repair after lung injury, we evaluated the capacity of neonatal AMs to secrete 92 kD Type IV collagenase. AMs were obtained by bronchoalveolar lavage from newborn rats at different postnatal ages. Total gelatinase activity was measured by zymography in AM-conditioned media. Spontaneous secretion of gelatinase from AMs varied significantly with age, the highest levels being found immediately after birth. Stimulation of AMs by PMA induced a four- to fivefold greater increase in total gelatinase activity during the first 10 d of postnatal life compared with adulthood. Using [3H]gelatin as the substrate, we found high free gelatinase activity only within 24 h after birth; data obtained after exposing cells to natural surfactant suggested that surfactant may account in part for this increase in free gelatinase activity. No secretion of tissue inhibitor of metalloproteinases (TIMP) by AMs was detectable in newborns within 24 h after birth. We conclude that AMs from newborn rats are able to secrete more gelatinase than AMs from adults, and this enzyme production profile during the neonatal period may contribute to the fact that newborns with lung injury are at high risk for extracellular matrix degradation.

Animals↗
PubMed1995

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗
PubMed1995

Forced oscillation technique vs spirometry to assess bronchodilatation in patients with asthma and COPD.

The forced oscillation technique (FOT) is a noninvasive test used to characterize the mechanical impedance of the respiratory system. The aim of the study was to compare the changes in respiratory conductance (Grs) measured with FOT to those in FEV1 in 22 patients with asthma and 20 patients with chronic obstructive pulmonary diseases (COPD) after salbutamol inhalation. FEV1 and Grs indexes, computed as the ratio of the difference between postbronchodilator and prebronchodilator values over the predicted value, were used to express reversibility of airway obstruction. After inhalation of salbutamol in cumulative doses up to 1,200 micrograms in ten patients of each group, FEV1 and Grs indexes showed parallel changes, and most of the increase was observed after the first dose of 200 micrograms of salbutamol for the two indexes. In all the 42 patients, we found a linear relationship between the two indexes after inhalation of 200 micrograms of salbutamol (r = 0.7, p < 0.0001). We evaluated FEV1 and Grs indexes in terms of sensitivity and specificity for identifying asthmatics among patients with COPD: using a 10% change as the cut-off value, these indexes proved of similar value (sensitivity, 0.91 and 0.95; specificity, 0.95 and 0.85, respectively). We conclude that the use of FOT can be considered as an alternative to forced expiration for detecting bronchodilatation in asthmatics and patients with COPD.

Airway Resistance↗
PubMed1994

Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs.

Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS). The control group was given 0.9% NaCl. 24 h after instillation, a BAL was performed, the BAL fluid was separated from the cells by centrifugation, and AMACs and PMNs were separately cultured for 24 h. In BAL fluid from LPS-treated guinea pigs, we found 1) an increase in free gelatinase activity, tested on [3H]gelatin (0.7 +/- 0.2 micrograms.200 microliters BAL fluid-1.48 h-1 vs. 0.2 +/- 0.1 in controls, P < 0.05), and 2) increased total gelatinase activities, as assessed by zymography. The molecular masses of the major gelatinase species found in BAL fluid by zymography were 92 and 68 kDa. The 92-kDa gelatinase was secreted by both AMACs and PMNs, as demonstrated by zymography of their respective culture media. When tested on [3H]elastin, the elastase activity of BAL fluid of LPS-treated animals exhibited no increase, but when tested on a synthetic peptidic substrate [N-succinyl-(L-alanine)3-p-nitro anilide (SLAPN)], increased elastase-like activity was observed (from 17 +/- 4 nmol of SLAPN.200 microliters BAL fluid-1.24 h-1 in control group to 34 +/- 8 in LPS group, P < 0.05). This increase was attributable to the activity of a metalloendopeptidase that was inhibited by the metal chelator EDTA but not by the specific tissue inhibitor of MMPs.

Animals↗
PubMed1994

Acute and chronic respiratory effects of sulfur mustard intoxication in guinea pig.

Sulfur mustard (SM) has been used as a vesicant chemical warfare agent. To investigate the respiratory damages it causes, we studied the effects on guinea pigs of an intratracheal injection of 0.3 mg/kg of SM 5 h and 14 days after injection. Five hours after SM intoxication, respiratory system resistance and microvascular permeability were increased. These alterations were not prevented by pretreatment with 50 mg/kg sc of capsaicin 2 wk before SM intoxication. Histological studies showed columnar cell shedding all along the tracheal epithelium, bronchoconstriction, and peribronchial edema. Fourteen days after SM intoxication, guinea pigs demonstrated airway hyperreactivity to aerosolized substance P and histamine. Pretreatment with phosphoramidon caused a further increase in airway responsiveness to substance P. Neutral endopeptidase activity in the tracheal epithelium was decreased by twofold in SM-intoxicated guinea pigs. At this stage, the tracheal epithelium was disorganized and atrophic. These results demonstrate that in guinea pigs SM intoxication induces severe lesions to the tracheal epithelium, which might account for the airway hyperresponsiveness observed 14 days after intoxication.

Acetylcholine↗
PubMed1994

Glucocorticoids inhibit sulfur mustard-induced airway muscle hyperresponsiveness to substance P.

To explore the mechanisms of airway hyperreactivity to aerosolized substance P observed in guinea pigs 14 days after intratracheal injection of sulfur mustard (SM), we studied the effects of epithelium removal and inhibition of neutral endopeptidase (NEP) activity on airway muscle responsiveness. Tracheal rings from SM-intoxicated guinea pigs expressed a greater contractile response to substance P than rings from nonintoxicated guinea pigs. After epithelium removal or incubation with the NEP inhibitor phosphoramidon, the contractile responses of tracheal rings to substance P did not differ in guinea pigs injected with SM or ethanol (SM solvent). Treatment of the guinea pigs with betamethasone for 7 days before measurement abolished the airway muscle hyperresponsiveness observed in untreated SM-intoxicated guinea pigs and partially restored tracheal epithelium NEP activity. In addition, the tracheal epithelium height and cell density of SM-intoxicated guinea pigs treated with betamethasone were significantly greater than in those without betamethasone. These results demonstrate that SM intoxication induces airway muscle hyperresponsiveness to substance P by reducing tracheal epithelial NEP activity and that glucocorticoids might inhibit this hyperresponsiveness by increasing this activity.

Administration, Inhalation↗
PubMed1994

Effects of capsaicin on the airway responses to inhaled endotoxin in the guinea pig.

Inhalation of lipopolysaccharide (LPS) has been associated with increased airway responsiveness and inflammation both in humans and in animals. To investigate the contribution of capsaicin-sensitive nerves to these changes, we compared airway responsiveness and inflammation after intratracheal administration of 10 micrograms/kg LPS (Escherichia coli O55:B5 lipopolysaccharide) or saline in guinea pigs treated 10 days previously with 50 mg/kg capsaicin and in those pretreated with the capsaicin vehicle. Four hours after LPS, airway responsiveness and cell counts in the bronchoalveolar lavage were assessed. To determine airway responsiveness, guinea pigs were anesthetized, tracheotomized, and mechanically ventilated before exposure to increasing concentrations of aerosolized histamine (10(-4) to 10(-3) M). Capsaicin pretreatment prevented the LPS-induced increase in airway responsiveness in response to aerosolized histamine. It significantly reduced total cell recovery in the bronchoalveolar lavage after LPS (1,167 +/- 167 10(3) cells/ml in capsaicin-treated guinea pigs versus 2,171 +/- 184 10(3) in vehicle-treated guinea pigs) by reducing the LPS-induced influx of neutrophils and macrophages. Additional experiments demonstrated that the activity of neutral endopeptidase (NEP) in the tracheal epithelium was not significantly different in guinea pigs injected with LPS from that in the saline-treated control animals, and that the pretreatment with the NEP inhibitor phosphoramidon did not increase the LPS-induced influx of neutrophils into the bronchoalveolar lavage. These results demonstrate that in the guinea pig, capsaicin-sensitive nerves are involved in LPS-induced airway hyperresponsiveness and inflammation.

Administration, Inhalation↗
PubMed1993

Bronchoconstriction-induced hyperinflation assessed by thoracic area measurement in guinea pigs.

The changes in end-expiratory lung volume (EELV) accompanying histamine-induced bronchoconstriction were compared for two routes of drug administration in anesthetized, paralyzed, and mechanically ventilated guinea pigs. Changes in EELV were estimated from measurements of thoracic cross-sectional area, assessed from the voltage induced by an external uniform magnetic field in a pickup coil encircling the rib cage. Increasing doses of histamine were administered as bolus injections in Group 1 (n = 7) and as nebulizations in Group 2 (n = 7). After each bronchial challenge, the maximum change in EELV and the associated intrinsic positive end-expiratory pressure (PEEPi) were measured at the same time. In both groups, bronchoconstriction was accompanied by an increase in EELV, which was related to the degree of bronchoconstriction and reached about 70 to 100% of the basal functional residual capacity. The increases in EELV were linearly related to the PEEPi values (p < 0.001) and did not depend on the route of histamine administration. These results indicate that dynamic hyperinflation is not the only mechanism involved in lung volume response to bronchoconstriction and suggest that gas trapping may have occurred in alveolar spaces.

Administration, Inhalation↗