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Biomedical subjects

F Chabot

Publications and source records attributed to F Chabot.

At least 37 records · Page 2Linked to original sources
PubMed1998

Reactive oxygen species in acute lung injury.

The acute respiratory distress syndrome (ARDS) in adults is associated with a wide variety of precipitating factors, often not directly involving the lung, and has an associated mortality of 50-80%. ARDS is almost invariably associated with sepsis, either as an initiating factor or as a secondary complication, which increases the expression of a number of cytokines impacting upon several cellular systems. Specifically, activation of neutrophils sequestered in the pulmonary circulation by this process, causes the release of free radicals and reactive oxygen species (ROS), increasingly regarded as key substances modulating the endothelial dysfunction and disruption responsible for the principal clinical manifestations of the syndrome. Here we discuss briefly the pathophysiology of ARDS and its impact upon pulmonary vascular control; the biological origins of free radicals and other ROS involved, the mechanisms of their damaging effects, their contribution to the modification of pulmonary vascular control mechanisms in lung injury and possible therapeutic perspectives.

Adult↗
PubMed1997

Characterization of the vasodilator properties of peroxynitrite on rat pulmonary artery: role of poly (adenosine 5'-diphosphoribose) synthase.

1. The pulmonary vasculature is constantly exposed to oxygen and reactive oxygen species such as nitric oxide (NO) and superoxide anions which can combine at a near diffusion limited rate, to form the powerful, oxidant, peroxynitrite (ONOO-). When formed in large amounts, ONOO- is thought to contribute to tissue injury and vascular dysfunction seen in diseases such as the acute respiratory distress syndrome (ARDS) and septic shock. Recent studies have shown that ONOO- can cause vasodilatation and at higher concentrations can activate poly (adenosine 5'-diphosphoribose) synthase (PARS) leading to consumption of nicotinamide adenine dinucleotide (NAD+) and adenosine 5'-triphosphate (ATP). As the lung represents a prime site for ONOO- formation, we characterized its effects on pulmonary vascular tone and on endothelial function. In addition, we have assessed the role of PARS in producing the vasoactive properties of ONOO- on pulmonary artery rings. 2. Isolated pulmonary artery rings from rats were mounted in organ baths containing warmed and gassed (95% O2: 5% CO2) Krebs buffer. Force was measured with isometric force transducers. After equilibration, ONOO- (10 nM-100 microM) was added in a cumulative manner. In separate experiments designed to assess any vasodilator properties of ONOO-, tissues were pre-contracted with the thromboxane mimetic U46619 (1 microM). Once a stable base-line was achieved, ONOO- was added in a cumulative fashion. ONOO- had no significant effect on resting pulmonary artery tone but caused concentration-dependent relaxations of pre-contracted vessels in the range 1 microM to 100 microM. In some experiments the effects of freshly prepared ONOO- solutions were compared with those allowed to decay at 4 degrees C for 2 days. 3. In some experiments either vehicle or ONOO- (1, 10 or 100 microM) was added for 15 min before U46619 (1 microM). Concentration-response curves to the endothelium-dependent vasodilator, acetylcholine (10 nM-100 microM) were then constructed. In these experiments, ONOO- (1 microM or 10 microM) had no effect on the actions of acetylcholine. However, at the highest concentration tested (100 microM), ONOO- increased acetylcholine-induced relaxations. 4. The vasodilator actions of ONOO- were unaffected by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) or by removal of superoxide anions with superoxide dismutase (SOD) (30 units ml-1). However, the relaxations induced by ONOO- were significantly inhibited by the PARS inhibitor, 3-aminobenzamide (10 microM). In contrast to its effects on ONOO-, 3-aminobenzamide had no effect on the relaxation caused by acetylcholine or sodium nitrite, but actually increased that induced by sodium nitroprusside. 5. These data show that ONOO- causes vasodilatation of rat pulmonary arteries, probably via activation of PARS. Moreover, at concentrations where relaxation was achieved, ONOO- did not affect the ability of pulmonary artery rings to relax to acetylcholine. We propose that ONOO-, but not endothelially derived NO, activates PARS resulting in the rapid depletion of ATP and a consequent reduction in contraction as well as other active processes of vascular smooth muscle. The finding that 3-aminobenzamide inhibited the actions of ONOO- but not acetylcholine, suggests that NO and ONOO- cause relaxation by independent mechanisms. It has been suggested that ONOO- is responsible for the vascular hyporesponsiveness to constrictor agents seen in experimental sepsis. This observation together with our current finding, that 3-aminobenzamide inhibits the relaxation induced by ONOO- but not by acetylcholine, suggests that inhibitors of PARS may reduce the persistent hypotension seen in sepsis without affecting the actions of endothelium-derived NO. Thus, the use of PARS inhibitors may represent a novel therapeutic approach to the treatment of septic shock.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Changes in peripheral pulmonary vascular resistance after ioxaglate infusion in anesthetized dogs.

The pulmonary vascular resistance in a peripheral portion of the pulmonary vascular bed can be determined with a catheter wedged in a peripheral branch of the pulmonary artery, from the pressure increase induced by infusion of mixed venous blood at known flow rates. The volume of the wedged vascular bed can be estimated during fluoroscopy, from the volume of a contrast agent infused until the corresponding pulmonary vein can be seen. The present work was undertaken to determine the possible influence of this maneuver on the peripheral pulmonary vascular resistance (PPVR). In anesthetized dogs, after a control flow run, Hexabrix (meglumine ioxaglate and sodium ioxaglate) was infused, then the catheter was flushed with saline, and another flow run was performed. There was no significant difference between two consecutive control runs in the same site (n = 14). Before Hexabrix (n = 23), PPVR was 162 (+/-24) x 10(3) dyn.s.cm-5 (1 dyn = 10 microN) during the control run; it increased to 339 (+/-33) x 10(3) dyn.s.cm-5 after Hexabrix (p < 0.001). These results show that care should be taken to avoid interference between Hexabrix and the results of physiological or pharmacological interventions with this technique.

Animals↗
PubMed1996

Role of NO in the pulmonary artery hyporeactivity to phenylephrine in experimental biliary cirrhosis.

The aim of this study was to see whether increased activity of nitric oxide (NO) might account for decreased pulmonary vascular tone seen in the hyperdynamic circulation of cirrhosis. We compared the pulmonary vascular reactivity of isolated pulmonary arteries (PA) from control rats (n = 10), and rats with biliary cirrhosis (n = 10) induced by chronic bile duct ligation (4 weeks). The responses of PA rings to cumulative concentrations of phenylephrine, acetylcholine, and sodium nitroprusside were studied, and also the effects of inhibition of synthesis of NO by the L-arginine analogue, N omega-nitro-L-arginine (L-NOARG) in PA rings challenged with cumulative concentrations of phenylephrine and acetylcholine. The contractile response to phenylephrine was significantly reduced in cirrhotic PA rings as compared with controls. Pretreatment with L-NOARG (10(-4) M) significantly increased the contractile response to phenylephrine in PA rings from cirrhotic rats but not in control PA rings. Furthermore, L-NOARG restored the response to phenylephrine in cirrhotic PA rings back to normal. There was no difference in the relaxation of PA rings from both groups in response to acetylcholine and sodium nitroprusside. We conclude that in vitro pulmonary artery ring hyporeactivity to phenylephrine results from increased nitric oxide production in the pulmonary circulation of cirrhotic rats and might account for the hepatopulmonary syndrome.

Acetylcholine↗
PubMed1996

[Fibrosing pneumopathy caused by labetalol].

A diffuse interstitial pulmonary fibrosis occurred in a 74-year-old woman treated for ten years with labetalol for systemic hypertension. Bronchoalveolar lavage (BAL) revealed lymphocytic and neutrophilic alveolitis. The lack of another etiologic factor and the spontaneously favorable course after withdrawal of the drug support the hypothesis of a labetalol induced pulmonary fibrosis.

Adrenergic beta-Antagonists↗
PubMed1995

[Pulmonary arterial hypertension: medical treatment and surgical indications].

Pulmonary hypertension is characterized by a poor prognosis which, therefore, justifies its treatment. Pulmonary vascular endothelium plays a pivotal role in the underlying mechanisms of different forms of pulmonary hypertension. Various paracrine factors, including nitric oxide, prostacyclin and endothelium-1, are synthesized by the endothelium. Nitric oxide and prostacyclin are powerful vasodilators, which also inhibit vascular smooth muscle proliferation and platelet aggregation. Endothelium-1 is probably one of the most potent vasoconstrictor known to date. The net effect of endothelial dysfunction results in increased vasoconstriction, platelet aggregation and occurrence of thrombosis, whereas vasodilatation is impeded. In primary pulmonary hypertension, acute pulmonary vasodilatation is currently sought using inhaled nitric oxide, oral calcium channel blockers or infused prostacyclin to predict the long-term effects of pulmonary vasodilators which might improve the quality of life and survival in some patients. Similar result could be obtained with anticoagulation. The most common cause of secondary pulmonary hypertension is alveolar hypoxia associated with chronic lung diseases. Long-term oxygen therapy improves survival and partially reverses the development of pulmonary hypertension. In chronic thromboembolic pulmonary hypertension, therapy includes anticoagulation and, in the case of lower limb venous thrombosis, inferior vena cava filtration. On the other hand, selected subsets of patients can undergo thromboendarterectomy. If the latter is contraindicated, lung transplantation is the only remaining curative treatment. However, lung transplantation should only be performed in end-stage diseased patients. Inclusion criteria are similar to those applied for primary pulmonary hypertension. The respective indications of heart-lung, double lung, and single lung transplantation, in primary or chronic thromboembolic pulmonary hypertension, remain to be evaluated.

Endothelium, Vascular↗
PubMed1995

Effect of acute hypercapnia on alpha atrial natriuretic peptide, renin, angiotensin II, aldosterone, and vasopressin plasma levels in patients with COPD.

Disturbances in hormonal systems involved in sodium and water homeostasis are common during respiratory insufficiency. To investigate the role of hypercapnia, we designed a study to examine the hormonal response to acute hypercapnia induced at constant cardiac filling pressures and without hypoxemia. Seven sedated patients with COPD receiving mechanical ventilation were studied during five successive periods. Hemodynamics, arterial blood gases, and plasma hormone levels (atrial natriuretic peptide, renin, angiotensin II, aldosterone, vasopressin) were measured three times during 60 min of acute hypercapnia (52 +/- 5 mm Hg) and at control periods, before (36 +/- 4 mm Hg) and after (42 +/- 3 mm Hg) acute hypercapnia. During acute hypercapnia, mean pulmonary arterial pressure and cardiac output were increased without variation of other measured cardiorespiratory data and hormonal levels when compared with control values. After acute hypercapnia, cardiorespiratory variables returned to control values without variations of hormonal levels. Our results show that moderate acute hypercapnia does not significantly influence the hormonal levels when cardiac filling pressures and sympathetic tone remain stable. We suggest that changes in those plasma hormones involved in salt and water homeostasis during acute hypercapnia are secondary to hemodynamic changes induced by acute respiratory failure and not to acute hypercapnia per se.

Aged↗
PubMed1995

[Methotrexate pneumonitis arising during the treatment of non-Hodgkin's lymphomas with the m-BACOD protocol].

We retrospectively studied 32 patients treated with the m-BACOD regimen in a single institution between January 1988 and December 1991. After four to seven courses, four patients presented severe acute pneumonitis (PaO2 < 55 mmHg in room air), with diffuse bilateral interstitial syndrome. Broncho-alveolar lavage displayed increased lymphocyte count (> 45%) with inversion of CD4/CD8 in two cases and no evidence of parasitic, bacterial or viral infection. All patients received methyl-prednisolone (0.5 to 1 mg/kg/d x 1 week) with both complete clinical and radiological recovery within a week. The m-BACOD regimen was continued without bleomycine for four patients and without bleomycine plus methotrexate for two patients, until the completion of eight courses, without recurrence of pneumonitis. Drug-exclusion decisions were made empirically because the exact nature of the pneumonitis was not recognized at the time of diagnostic. Because of the regular administration in the m-BACOD regimen, methotrexate leads to an increased risk of pneumonitis. We concluded that the use of the m-BACOD regimen should henceforth be discontinued.

Adult↗
PubMed1995

[Contribution of bronchoalveolar lavage and transbronchial biopsy to diagnosis and prognosis of drug-induced pneumopathies].

This survey reports on 10 case-studies of drug-induced pneumonitis. The drugs under consideration are amiodarone, methotrexate, chlorambucil, sulindac, nilutamide-leuproreline, cyclothiazide, with the possible addition of bleomycin. In each case, one or more bronchoalveolar lavage were carried out and in most cases it was also possible to perform a transbronchoscopic lung biopsy. The results of these tests are analysed in order to ascertain their contribution to diagnosis and prognosis. Regarding diagnosis, bronchoalveolar lavage does not evidence a typical cellular configuration characterizing drug-induced alveolitis. Moreover, transbronchoscopic lung biopsy plays no part in diagnosing this pathology. Both these tests, however, help to eliminate other hypotheses. Regarding prognosis, transbronchoscopic lung biopsy provides no information, unlike bronchoalveolar lavage in which a high rate of neutrophils in the lavage fluid is sometimes associated with the development of pulmonary fibrosis.

Acute Disease↗
PubMed1995

[New imaging techniques in pulmonary embolism].

Acute pulmonary embolism is a medical emergency and diagnostic certitude must be obtained as early as possible. In clinically serious situations, spiral CT is a reliable diagnostic tool. It provides direct signs of embolism with visualisation of thrombi in the pulmonary arteries as far as the segmental branches and its diagnostic value does not change in cases of pulmonary parenchymal involvement. In emergencies, spiral CT should replace pulmonary angiography, which is more costly and associated with greater morbidity and mortality. Other methods, in particular MRI, which is totally innocuous, could play an important role in the diagnostic strategy of acute pulmonary embolism in the near future.

Diagnostic Imaging↗
PubMed1994

Interleukin-6, interferon-gamma, and phospholipid levels in the alveolar lining fluid of human lungs. Profiles in coal worker's pneumoconiosis and idiopathic pulmonary fibrosis.

Cytokines are widely involved in physiologic as well as immunoinflammatory and fibrosing processes of the lung. The aim of this work was to study, by bronchoalveolar lavage, two groups of human interstitial lung diseases (ILD) with fibrosing propensity (ie, idiopathic pulmonary fibrosis [IPF], n = 10; and coal worker's pneumoconiosis [CWP], n = 15). Patients were compared with nonsmoker control subjects (n = 20). Cellularity, proteins, and phospholipids were determined in the alveolar fluids. In addition, two cytokines (interleukin-6 [IL-6] and interferon-gamma [IFN-gamma]), which are presumed to possess respective antifibrotic and profibrotic activities, were measured in the respiratory tract. Compared with control subjects, IPF and simple CWP showed alveolar hypercellularity (p < 0.05) and relative lymphocytosis (p < 0.05). Both exhibited increased alveolar permeability (ie, increased albumin/urea ratio, p < 0.05), with enhanced IL-6 and decreased IFN-gamma in the alveolar spaces (p < 0.05). On the other hand, IPF displayed an associated polymorphonuclear alveolitis, enhanced alveolar epithelial lining fluid (AELF) volume and low surfactant phospholipid levels (p < 0.05 vs control), whereas simple CWP shared an exclusive lymphocytosis, normal AELF volume, and a surfactant lipid overflow (p < 0.05 vs control). Relationships among all of these parameters were found only between alveolar cellularity, neutrophils and IL-6 levels in the AELF of IPF (respectively, r = 0.85, p = 0.0009, and r = 0.89, p = 0.0006). In summary, common alterations of cellular and cytokine turnover were observed in IPF and simple CWP and may reflect activity of the antifibrotic fight in these diseased lungs. Surfactant phospholipid levels are likely to represent a specific disturbance among IPF and CWP, but no clear relationship with respect to the other parameters could be established for explaining the difference in time course outcome.

Adult↗
PubMed1994

Loss of lymphocyte modulatory control by surfactant lipid extracts from acute hypersensitivity pneumonitis: comparison with sarcoidosis and idiopathic pulmonary fibrosis.

Surfactant components are recognized to exert a regulatory control on lymphocytes in physiological conditions, as testified by in vitro studies. However, what happens following lung injury has not been established. As surfactant composition is altered in interstitial lung diseases, this work was carried out to compare the modulatory impact of normal human alveolar fluids on lymphocyte proliferation, with that from inflammatory lung diseases which are characterized by distinct patterns of immunologically-mediated alterations (i.e. sarcoidosis, acute hypersensitivity pneumonitis, idiopathic pulmonary fibrosis). Thymidine incorporation of allogeneic normal human blood lymphocytes was studied in the presence of total alveolar fluids or lipid extracts from 37 subjects, and phytohaemagglutinin (PHA) as T-cell mitogen. The results show that: 1) total alveolar fluids and lipid extracts from normal subjects share a concentration-dependent suppressive activity on T-cell proliferation; 2) total alveolar fluids from diseased patients have lost this property, either by a lack of suppressive activity (i.e. idiopathic pulmonary fibrosis) or even by enhanced activity (i.e. sarcoidosis and hypersensitivity pneumonitis); 3) lipid extracts from diseased patients still retain the suppressive activity of normal subjects, except for hypersensitivity; and 4) an imbalance in surfactant phospholipids with an increase in the inducers to suppressors ratio is more likely to explain this alteration in hypersensitivity pnuemonitis than changes in total lipid content. In conclusion, alveolar lipid extracts from acute hypersensitivity pnuemonitis have lost the modulatory control normally exerted by surfactant lipids on lymphocyte proliferation in vitro. This alteration may contribute to the invasion of the lung by lymphocytes in acute hypersensitivity pnuemonitis in vivo.

Adult↗
PubMed1993

Early effects of short-time cigarette smoking on the human lung: a study of bronchoalveolar lavage fluids.

We investigated the early effects of cigarette smoking in healthy subjects by means of lung lavage, looking at markers of alveolar permeability, the alveolar cell profile, the immunophenotyping of macrophages and lymphocytes, and the level and profile of surfactant phospholipids. Bronchoalveolar lavages (BAL) were performed in 33 healthy subjects [20 nonsmokers (nS), 13 moderate and short-time smokers (S)]. In the acellular supernatants we measured the markers of alveolar permeability (i.e., total proteins, albumin, albumin/urea), the alveolar epithelial lining fluid (AELF), the surfactant amounts and profile, and explored the blood lymphocytes by in vitro exposure. The cell pellet established the alveolar formula and a membrane mapping of macrophages (LFA-1 and HLA-DRII expression) and lymphocytes (CD4, CD8, LFA-1, HLA-DRII expression). We found no significant increase of alveolar permeability in our smokers, but an increased alveolar cellularity (more than 3-fold vs nS, P < 0.05) evenly distributed between sub-populations except for an enhanced number of eosinophils in smokers (P < 0.05 vs nS). Smokers' alveolar macrophages had an overloaded cytoplasm, a decreased percentage of antigen-handling cell expression (HLA DRII: P < 0.05 vs nS) and a low percentage of cell to cell adhesion molecule expression (LFA-1: P < 0.05 vs nS). Smoking history and LFA-1 expression on alveolar macrophages were interrelated. Smokers' alveolar lymphocyte subsets were more often T suppressor cells (CD8+) and had an increased percentage of antigen-presenting cell expression (HLA DRII: P < 0.05 vs nS). Smokers' BAL fluid did not show the inhibitory control of phytohemagglutinin-induced lymphocyte proliferation present in nonsmokers' fluids. Surfactant phospholipid amounts were similar, but phosphatidylethanolamine was raised and the ratio of phosphatidylcholine to sphingomyelin decreased in smokers (P < 0.05 vs nS). We observed specific cellular and biochemical alterations in the lung lavage of short-time smokers. Alveolar macrophage and lymphocyte expression of LFA-1 and HLA-DR II molecules was altered. Smokers' alveolar fluids lost the physiologic regulatory control of T mitogen-induced lymphocyte proliferation. Membrane phospholipids released by cellular damage increased early in tobacco-exposed lung fluids. This profile of alterations may be an early and sensitive marker of smoking-induced lung damage.

Adult↗
PubMed1993

Pulmonary arterial wedge pressure measurement can modify pulmonary haemodynamics in patients with chronic lung disease.

In 20 patients with chronic lung disease in stable condition, haemodynamic values were compared during wedging of a Swan-Ganz catheter, either in a distal branch of the pulmonary artery, or by balloon inflation (with 1 ml) in a proximal branch, mostly excluding right lower lobe perfusion. Average pulmonary arterial wedge pressure, systemic arterial pressure, transcutaneous and mixed venous oxygen saturation, cardiac output and pulmonary blood volume (PBV) were not statistically different during distal and proximal wedging, but systolic pulmonary arterial pressure and pulmonary vascular resistance were slightly higher during balloon inflation (P < 0.05). In four patients, PBV decreased by 20% or more; cardiac output was reduced and mean systemic arterial pressure diminished by 10 mmHg or more in three patients. Of the two patients with the lowest PBV, one did not tolerate the balloon inflation because of dyspnoea, and the other showed dramatically haemodynamic changes. These were more likely to occur when the occlusion lead to the exclusion of a still well perfused area. Our results support optimal matching between ventilation and perfusion in patients with chronic lung disease, although both are inhomogeneous. When pulmonary vascular restriction can be suspected, pressure obtained during catheter wedging by balloon inflation should be interpreted with caution. Monitoring arterial oxygen saturation and systemic arterial pressure before and during the manoeuver could help to diagnose haemodynamic effects of the balloon inflation in a proximal pulmonary artery.

Adult↗
PubMed1993

Right ventricular pressure-volume relations in chronic lung disease.

Thirty-four patients with chronic lung disease in stable condition were studied at supine rest (RS), at rest with the legs raised (LR), and during two levels of exercise: E1, 0 or 20 W, E2, 20 or 40 W. Five patients had normal spirometry (group 1), six patients had normal vital capacity but FEV1/VC below 70% (group 2), and 23 patients had VC below 95% of normal and FEV1/VC below 70% (group 3); group 3 was subdivided into group 3a (n = 14) without, and group 3b (n = 9) with a history of right heart failure (RHF). Right ventricular end-diastolic (RVEDV) and end-systolic (RVESV) volumes were computed from stroke volume and right ventricular ejection fraction (RVEF). RVEF at rest was correlated with lung function variables. Changes in RVEF from LR to E2 were normal, i.e. above 0.05, except for in group 3b, where RVEF did not increase with exercise. Relation between RVESV and pressure, and changes in stroke volume with RVEDV from LR to E2 were also abnormal in group 3b. These results show that in patients with chronic lung disease RVEF at rest reflects lung function, whereas its adaptation to exercise is impaired only in patients who have experienced RHF episodes.

Blood Pressure↗
PubMed1993

Peripheral pulmonary vascular resistance.

The pressure-flow relationship has been studied in a peripheral portion of the lung vasculature in anesthetized dogs with use of a double-lumen catheter wedged in a distal pulmonary artery. One lumen was used to infuse mixed venous blood in the wedged area and the other to measure the corresponding perfusion pressure. Flow ranged from 0 to 9.2 ml/min, and the mean volume of the wedged area (n = 59) was 0.75 +/- 0.05 (SE) ml. In the areas where the distal pulmonary artery was in the same direction as the catheter ("coaxial"), the mean pressure-flow curve showed a negligible gamma-intercept and no significant difference between ascending and descending flow. The slope of the initial part of the ascending limb (peripheral pulmonary vascular resistance) varied from site to site and did not show a significant correlation with the overall pulmonary vascular resistance; it was inversely correlated with the volume of the wedged area (r = -0.35, P < 0.05) and directly, as expected, correlated with the y-intercept (r = 0.78, P < 0.001) and hysteresis (r = 0.48, P < 0.001). The results of two consecutive pressure-flow runs in the same site showed similar results, with no difference exceeding the error of measurement. In contrast, the slope increased by 71% during hypoxia (fraction of inspired O2 was 0.10, n = 5). This procedure seems suitable to determine the effects of physiological or pharmacological interventions on the pulmonary vessels, without interference of the systemic circulation.

Animals↗