Biomedical subjects

J Boczkowski

Publications and source records attributed to J Boczkowski.

At least 19 recordsLinked to original sources

PubMed2006

Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample. Results from the European Community Respiratory Health Survey (ECRHS), France.

Inducible heme oxygenase (HO-1) acts against oxidants that are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD), characterised by impaired lung function. A (GT)(n) repeat polymorphism in the HO-1 gene promoter can modulate the gene transcription in response to oxidative stress. We hypothesised that this polymorphism could be associated with the level of lung function and decline in subjects exposed to oxidative aggression (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced ventilatory capacity (FVC) ratio. We compared long (L) allele carriers ((GT)(n) > or =33 repeats for one or two alleles) to non-carriers. Cross sectionally, in 2000, L allele carriers showed lower FEV1/FVC than non-carriers. During the 8 year period, the mean annual FEV1 and FEV1/FVC declines were -30.9 (31.1) ml/year and -1.8 (6.1) U/year, respectively. FEV1/FVC decline was steeper in L allele carriers than in non-carriers (-2.6 (5.5) v -1.5 (6.4), p = 0.07). There was a strong interaction between the L allele and smoking. In 2000, the L allele was associated with lower FEV(1) and FEV(1)/FVC in heavy smokers (> or =20 cigarettes/day) only (p for interaction = 0.07 and 0.002 respectively). Baseline heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 (29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 (5.4 U/year) (p for interaction = 0.009 and 0.0006). These results suggest that a long (L) HO-1 gene promoter in heavy smokers is associated with susceptibility to develop airway obstruction.

Adult↗

PubMed2005

Carbon monoxide reduces the expression and activity of matrix metalloproteinases 1 and 2 in alveolar epithelial cells.

Matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-2, are involved in the pathophysiology of emphysema. MMPs contain zinc in the catalytic site and its expression is regulated transcriptionally via mitogen activated protein kinases (MAPKs). Carbon monoxide (CO), one of the end products of heme oxygenase activity, has anti-inflammatory properties, which are mediated, at least in part, by activation of p38 MAPK. Furthermore, CO has the unique ability to bind to metal centers in proteins and can affect their specific activity. Therefore, we hypothesized that CO could inhibit MMPs expression and/or activity. Here we show that a recently identified carbon monoxide-releasing molecule, [Ru(CO)3Cl2]2 (or CORM-2) inhibits MMP-1 and MMP-2 mRNA expression in the human lung epithelial cell line A549. The MMPs mRNA expression was unaffected by the p38 MAPK inhibitor SB203580, but in the case of MMP-1 was reversed by the antioxidant N-acetylcysteine. In addition, CORM-2 inhibited both MMP-1 and MMP-2 activities. Interestingly, no effect was observed with (Ru(DMSO)4Cl2), a negative control that does not contain CO groups. To the best of our knowledge this is the first evidence on the effect of CO on MMPs expression and activity. This effect could have important implications in the pathophysiology of emphysema and other diseases involving proteases/antiproteases imbalance.

Carbon Monoxide↗

PubMed2002

[Diaphragmatic weakness in sepsis: the role of oxidant stress].

In sepsis contractile weakness of the diaphragm is a major cause of the onset of respiratory failure. This muscular weakness is the result of haemodynamic and metabolic disorders secondary to sepsis and also the damaging effects of inflammatory mediators, among which oxygen free radicals play a crucial role. This role is demonstrated by the protective effect of various exogenous anti-oxidants on diaphragmatic contraction. Early in the course of sepsis there is, in animal models and in man, an increased production of oxygen free radicals and nitric oxide (NO) in the diaphragm, principally within the mitochondria. The formation of peroxinitrite as the result of the action of NO on superoxide anions impairs mitochondrial respiration and consequently the energy production necessary for diaphragmatic contraction. Among the endogenous anti-oxidant systems haem oxygenase, which splits haemoglobin into bilirubin, iron and carbon monoxide, is an effective system for the protection of diaphragmatic function by limiting the damage of oxidant stress. Nevertheless a transient deficiency of local anti-oxidant defences during the early stages of sepsis, when the production of oxygen free radicals is intense, encourages the onset of contractile weakness.

Animals↗

PubMed2001

Regulation of peroxisome proliferator-activated receptor gamma expression in human asthmatic airways: relationship with proliferation, apoptosis, and airway remodeling.

Airway inflammation and alterations in cellular turnover are histopathologic features of asthma. We show that the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear hormone receptor involved in cell activation, differentiation, proliferation, and/or apoptosis, is augmented in the bronchial submucosa, the airway epithelium, and the smooth muscle of steroid-untreated asthmatics, as compared with control subjects. This is associated with enhanced proliferation and apoptosis of airway epithelial and submucosal cells, as assessed by the immunodetection of the nuclear antigen Ki67, and of the cleaved form of caspase-3, respectively, and with signs of airway remodeling, including thickness of the subepithelial membrane (SBM) and collagen deposition. PPAR gamma expression in the epithelium correlates positively with SBM thickening and collagen deposition, whereas PPAR gamma expressing cells in the submucosa relate both to SBM thickening and to the number of proliferating cells. The intensity of PPAR gamma expression in the bronchial submucosa, the airway epithelium, and the smooth muscle is negatively related to FEV(1) values. Inhaled steroids alone, or associated with oral steroids, downregulate PPAR gamma expression in all the compartments, cell proliferation, SBM thickness, and collagen deposition, whereas they increase apoptotic cell numbers in the epithelium and the submucosa. Our findings have demonstrated that PPAR gamma (1) is a new indicator of airway inflammation and remodeling in asthma; (2) may be involved in extracellular matrix remodeling and submucosal cell proliferation; (3) is a target for steroid therapy.

Aged↗

PubMed2001

Decreased pulmonary and tracheal smooth muscle expression and activity of type 1 nitric oxide synthase (nNOS) after ovalbumin immunization and multiple aerosol challenge in guinea pigs.

Pharmacological evidence supports a role of a transient decreased endogenous nitric oxide (NO) synthesis in ovalbumin (OVA)-induced early airway hyperresponsiveness in guinea pigs. However, no data are available regarding the expression and activity of the constitutive NO synthases (cNOS; NOS1 and NOS3, nNOS and eNOS, respectively) in this model. Therefore, we evaluated cNOS activity (conversion of L-[3H]arginine to L-[3H]citrulline in the presence of Ca2+ and calmodulin), nitrate and nitrite (NOx) concentration (modified Griess method), and NOS1 and NOS3 protein expression (Western blot) in lung homogenates and in the tracheal smooth muscle from OVA-immunized and multiple aerosol-challenged guinea pigs (six challenges, once daily). The expression and activity of the inducible NOS isoform (NOS2), the levels of exhaled NO, and the in vivo airway reactivity were also determined. Constitutive NOS activity and NO(x) concentration were significantly lower 6 h after the last OVA challenge as compared with saline exposure, being similar at 24 h. Expression of NOS1 paralleled cNOS activity, which was reduced 6, but not 24 h after OVA challenge. The decrease in NOS1 expression was accompanied by a significant decrease in the amounts of exhaled NO and by a maximal airway hyperresponsiveness to histamine. The levels of NOS3 were not modified at the two time points evaluated, and no NOS2 expression and activity were found at any time point. Similar modifications were observed in the tracheal smooth muscle. We conclude that OVA stimulation in immunized guinea pigs induced a transient reduction in NOS1 protein expression and activity in the respiratory system, which probably participates in airway hyperresponsiveness.

Aerosols↗

PubMed2001

Effects of riluzole on N-methyl-D-aspartate-induced tyrosine phosphorylation in the rat hippocampus.

Since increased tyrosine phosphorylation has been observed in response to brain ischemia, we investigated whether riluzole (an inhibitor of glutamate neurotransmission with neuroprotective properties) affects tyrosine phosphorylation stimulated by N-methyl-D-aspartate (NMDA) in rat hippocampal slices. Riluzole produced an extremely potent concentration-related inhibition of NMDA (1 mM)-stimulated protein tyrosine phosphorylation (IC(50)=0.5+/-0.03 microM, mean+/-S.D.), but failed to affect that evoked by phorbol 12-myristate 13-acetate (PMA, an activator of protein kinase C, 0.1 and 1 microM). These results suggest that inhibition of tyrosine phosphorylation may contribute to the neuroprotective effects of riluzole against excitotoxic injury.

Animals↗

PubMed2001

Sepsis is associated with reciprocal expressional modifications of constitutive nitric oxide synthase (NOS) in human skeletal muscle: down-regulation of NOS1 and up-regulation of NOS3.

OBJECTIVE: To study the expression (mRNA and protein) and activity of the constitutive isoforms of nitric oxide synthase (NOS1 and NOS3) in a skeletal muscle of septic patients. DESIGN: Prospective study. SETTING: An adult trauma/surgical intensive care unit in an urban teaching hospital. PATIENTS: Sixteen septic patients and 21 controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Samples of the rectus abdominis muscle were obtained during surgical procedure. NOS mRNA, protein, and activity were detected by reverse-transcriptase polymerase chain reaction, Western blot, and the conversion of [3H]L-arginine to [3H]L-citrulline, respectively. The main results of this study are as follows: a) Levels of NOS1 mRNA and protein were significantly higher than those of NOS3 in the rectus abdominis muscle of control patients; b) NOS1 expression was down-regulated in septic patients, whereas NOS3 was up-regulated; c) these modulations were associated with a reduction in constitutive NOS activity; and d) modifications of NOS1 and NOS3 protein expression were correlated significantly with the severity of sepsis, assessed by the Simplified Acute Physiology Score II. CONCLUSIONS: Sepsis induces reciprocal expressional modifications of NOS1 and NOS3 in human skeletal muscle, which decreases muscular constitutive NOS activity. These modifications may have implications for muscle impairment in septic patients.

Caenorhabditis elegans Proteins↗

PubMed2001

Protective role of heme oxygenases against endotoxin-induced diaphragmatic dysfunction in rats.

Reactive oxygen species are strongly implicated in diaphragmatic dysfunction during sepsis. We investigated whether the heme oxygenase (HO) pathway, which is a powerful protective cellular system, protects the diaphragm against oxidative stress and contractile failure during sepsis. A basal expression of both the inducible and constitutive HO protein isoforms (HO-1 and HO-2, respectively) was found in the diaphragm. Enhanced HO-1 expression in diaphragmatic myocytes was observed 24 h after Escherichia coli endotoxin (lipopolysaccharide, LPS) inoculation and remained elevated for at least 96 h. Enhanced HO-1 expression was also observed in the rectus abdominis and soleus muscles and in the left ventricular myocardium of endotoxemic animals. Diaphragmatic HO-2 expression was not modified by endotoxin. Diaphragmatic HO activity exhibited a biphasic time course characterized by a transient decrease during the first 12 h followed by a significant increase at 24 h, corresponding to HO-1 induction. Diaphragmatic force was significantly reduced 24 h after LPS, concomitantly with muscular oxidative stress. Administation of an inhibitor of heme oxygenase activity, zinc protoporphyrin IX (ZnPP-IX), further impaired muscular oxidative stress and contractile failure. By contrast, increased levels of HO-1 expression obtained by pretreatment of rats with hemin, a powerful inducer of HO-1, completely prevented LPS-mediated diaphragmatic oxidative stress and contractile failure. This protective effect was reversed by ZnPP-IX. These results show an important protective role for the HO pathway against sepsis-induced diaphragmatic dysfunction, which could be related to its antioxidant properties.

Animals↗

PubMed2000

Anesthetic concentrations of riluzole inhibit neuronal nitric oxide synthase activity, but not expression, in the rat hippocampus.

We hypothesized that anesthetic dose of riluzole, an inhibitor of glutamate neurotransmission, may affect the activity and/or expression of neuronal NOS (nNOS). Riluzole, N(G)-nitro-L-arginine-methyl ester (L-NAME) and 7-nitro indazole (7-NI) produced a concentration-related inhibition of nNOS activity in vitro. Riluzole competed with 7-NI for inhibition of nNOS activity, but had no effect on nNOS or endothelial NOS (eNOS) protein expression. Also, nNOS activity was significantly decreased in riluzole-anesthetized rats (40 mg kg(-1) i.p., -32+/-6% from controls, P<0.05). Therefore, blockade of nNOS activity may be involved in the anesthetic effects of riluzole in vivo.

Actins↗

PubMed2000

Muscular contractile failure in septic patients: role of the inducible nitric oxide synthase pathway.

Skeletal muscle failure is a frequent manifestation of sepsis that affects prognosis and rehabilitation by impairing respiration and ambulation. Animal studies have shown that the inducible NO synthase (NOS2) is expressed in skeletal muscles during sepsis, likely affecting muscular function, by promoting the formation of the strong oxidant peroxynitrite. In contrast, whether human skeletal muscle expresses a functional NOS2 in similar conditions is unknown. We studied NOS2 expression (mRNA and protein) and activity and its role in contractile function in samples from rectus abdominis muscle obtained during surgical procedure in 16 septic patients and in 21 controls. Peroxynitrite formation was detected by immunohistochemical detection of nitrotyrosine residues. The main results of this study are as follows: (1) A significant increase in NOS2 mRNA, protein, and activity was found in muscles from septic patients, the expression of NOS2 protein positively correlating with sepsis severity. (2) Contractile force was significantly lower in septic than in control muscles. This phenomenon was not reverted by muscle incubation ex vivo with the NOS inhibitor L-NMMA, indicating that NO was not involved in force reduction at the time of biopsy. (3) NOS2 expression in skeletal myocytes was strongly co-localized with nitrotyrosine, revealing muscular peroxynitrite generation during the septic process, before the muscle was biopsied. Exposure of control muscles to an amount of peroxynitrite similar to that generated in septic muscles during the septic process resulted in a nonreversible reduction in force generation. These results suggest that NOS2 could be involved in the decreased muscular force of septic patients via the local generation of peroxynitrite.

Adult↗

PubMed2000

Flow limitation and dynamic hyperinflation during exercise in COPD patients after single lung transplantation.

STUDY OBJECTIVE: Using the negative expiratory pressure (NEP) method, we have previously shown that patients receiving single lung transplantation (SLT) for COPD do not exhibit expiratory flow limitation and have little dyspnea at rest. In the present study, we assessed whether SLT patients exhibit flow limitation, overall hyperinflation, and dyspnea during exercise. METHODS: Expiratory flow limitation assessed by the NEP method and inspiratory capacity maneuvers used to determine end-expiratory lung volume (EELV) and end-inspiratory lung volume (EILV) were performed at rest and during symptom-limited incremental cycle exercise in eight SLT patients. RESULTS: At the time of the study, the mean (+/- SD) FEV(1), FVC, functional residual capacity, and total lung capacity (TLC) amounted to 55 +/- 14%, 67 +/- 12%, 137 +/- 16%, and 110 +/- 11% of predicted, respectively. At rest, all patients did not experience expiratory flow limitation and were without dyspnea. At peak exercise, the maximal mechanical power output and maximal oxygen consumption amounted to 72 +/- 20% and 65 +/- 8% of predicted, respectively, with a maximal dyspnea Borg score of 6 +/- 3. All but one patient exhibited flow limitation and dynamic hyperinflation; the EELV and EILV amounted to 74 +/- 5% and 95 +/- 9% TLC, respectively. The patient who did not exhibit flow limitation during exercise had the lowest dyspnea score. CONCLUSION: Most SLT patients for COPD exhibit expiratory flow limitation and dynamic hyperinflation during exercise, whereas maximal dyspnea is variable.

Aged↗

PubMed2000

[Special characteristics of the diaphragm muscle cell].

The diaphragm is the main inspiratory muscle, accounting for more than 50% of the tidal volume during quiet breathing. It works continuously, contracting rhythmically and generally at a low intensity. In this respect, it is close to the myocardium, being the only vital skeletal muscle. From a general point of view, functional and biochemical characteristics of the diaphragm are similar to those of other skeletal muscles with a similar fiber type composition. However, the diaphragm presents some specificities allowing a high supply of metabolic substrates. This could serve to preserve contractile function in different physiological and physiopathological situations. Such specificities concern muscular vascularization, the microvascular network and the content of mitochondria and myoglobin. These characteristics are detailed and compared to those of other striated muscles.

Diaphragm↗

PubMed2000

[Role of nitric oxide in diaphragmatic dysfunction genesis during sepsis in rats].

Nitric oxide (NO) is a vasodilator agent that is cytotoxic and negatively inotropic in the heart. More recently, it has been shown that during sepsis there is a high amount of NO production by a NO synthase (NOS) that is inducible by cytokines. The aim of this study was to investigate the role of NO in the genesis of diaphragmatic dysfunction during sepsis. Rats were inoculated i.p. injection with 10 mg/kg of Escherichia coil endotoxin (E animals) or saline (C animals). Six hours after endotoxin or saline inoculation, diaphragmatic force and muscularc GMP (Cyclic guanosine monophosphate) were assessed by in vitro force frequency curves and ELISA method, respectively. As compared to C animals, E animals showed a significant decrease in diaphragmatic force for all the frequencies of stimulation (p < 0.01). This reduction was associated with a significant increase in muscular cGMP. Inhibition of NO synthesis in E animals with either dexamethasone (4 mg/kg IV, 45 min before endotoxin or saline) or NG-monomethyl-L-arginine (L-NMMA, 8 mg/kg IV, 90 min after endotoxin or saline) prevented the effects of endotoxin. However, no modification was seen with NG-monomethyl-D-arginine (D-NMMA), a molecule which does not inhibit NO synthesis. Administration of dexamethasone or L-NMMA in C animals did not induce any significant change in diaphragmatic force, and cGMP ratio. We conclude that NO has a contributive role in diaphragmatic dysfunction during Escherichia coli induced sepsis in rats.

Animals↗

PubMed1999

Endogenous peroxynitrite mediates mitochondrial dysfunction in rat diaphragm during endotoxemia.

It has been shown that nitric oxide (NO), synthesized by the inducible NO synthase (iNOS) expressed in the diaphragm during endotoxemia, participates in the development of muscular contractile failure. The aim of the present study was to investigate whether this deleterious action of NO was related to its effects on cellular oxidative pathways. Rats were inoculated with E. coli lipopolysaccharide (LPS) or sterile saline solution (controls) and studied at 3 and 6 h after inoculation. iNOS protein and activity could be detected in the rat diaphragm as early as 3 h after LPS, with a sustained steady-state concentration of 0.5 microM NO in the muscle associated with increased detection of hydrogen peroxide (H(2)O(2)). In vitro, the same NO concentration produced a marked increase in H(2)O(2) production by isolated control diaphragm mitochondria, thus reflecting a higher intramitochondrial concentration of nondiffusible superoxide anion (O(2)(-.)). In a similar way, whole diaphragmatic muscle and diaphragm mitochondria from endotoxemic rats showed a progressive increase in H(2)O(2) production associated with uncoupling and decreased phosphorylating capacity. Simultaneous with the maximal impairment in respiration (6 h after LPS), nitration of mitochondrial proteins (a peroxynitrite footprint) was detected and diaphragmatic force was reduced. Functional mitochondrial abnormalities, nitration of mitochondrial proteins, and the decrease in force were significantly attenuated by administration of the NOS inhibitor L-NMMA. These results show that increased and sustained NO levels lead to a consecutive formation of O(2)(-.) that reacts with NO to form peroxynitrite, which in turn impairs mitochondrial function, which probably contributes to the impairment of muscle contractility. during endotoxemia.

Animals↗

PubMed1998

Role of nitric oxide on diaphragmatic contractile failure in Escherichia coli endotoxemic rats.

Contractile dysfunction of the respiratory muscles plays an important role in the genesis of respiratory failure during sepsis. Nitric oxide (NO), a free radical that is cytotoxic and negatively inotropic in the heart and skeletal muscle, is produced in large amounts during sepsis by a NO synthase inducible (iNOS) by LPS and/or cytokines. The aim of this study was to investigate whether iNOS was induced in the diaphragm of Escherichia coli endotoxemic rats and whether inhibition of iNOS induction or of NOS synthesis attenuated diaphragmatic contractile dysfunction. Rats were inoculated intravenously (IV) with 10 mg/kg of E. coli endotoxin (LPS animals) or saline (C animals). Six hours after LPS inoculation animals showed a significant increase in diaphragmatic NOS activity (L-citrulline production, P < 0.005). Inducible NOS protein was detected by Western-Blot in the diaphragms of LPS animals, while it was absent in C animals. LPS animals had a significant decrease in diaphragmatic force (P < 0.0001) measured in vitro. In LPS animals, inhibition of iNOS induction with dexamethasone (4 mg/kg IV 45 min before LPS) or inhibition of NOS activity with N(G)-methyl-L-arginine (8 mg/kg IV 90 min after LPS) prevented LPS-induced diaphragmatic contractile dysfunction. We conclude that increased NOS activity due to iNOS was involved in the genesis of diaphragmatic dysfunction observed in E. coli endotoxemic rats.

Animals↗

PubMed1998

Theophylline dilates rat diaphragm arterioles via the prostaglandins pathway.

1. We investigated by intravital microscopy in rats, the in vivo direct effects of theophylline on the diameters of second and third order diaphragm arterioles. 2. Theophylline (1-100 microM) dilated second and third order diaphragm arterioles significantly, and with an amplitude which was not statistically different from the one obtained with adenosine (1-100 microM). Enprofylline (1-100 microM), a theophylline analogue with poor adenosine-receptor antagonism but with similar or higher phosphodiesterases inhibition properties than theophylline, also dilated diaphragm arterioles, causing however, a significantly smaller dilatation than theophylline. 3. Neither the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX, 50 nM), nor the A2 adenosine receptor antagonist 3,7-dimethyl-1-proparglyxanthine (DMPX, 10 microM) reduced significantly theophylline-induced arteriolar dilatation. 4. Theophylline (100 nM) abolished adenosine-induced arteriolar dilatation. 5. The dilatation induced by theophylline was unchanged by the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (NNA, 300 microM). 6. Theophylline-induced arteriolar dilatation was abolished by the prostaglandin synthesis inhibitors mefenamic acid or indomethacin (20 microM). 7. These findings show that theophylline induced a significant dilatation of diaphragm arterioles via the release of prostaglandins.

Adenosine↗

PubMed1998

Effects of etomidate, propofol and thiopental anaesthesia on arteriolar tone in the rat diaphragm.

We have assessed, by intravital microscopy in rats, the effects of different anaesthetics on diaphragmatic arteriolar diameter. Rats were anaesthetized with etomidate, propofol or thiopental (groups E, P and T, respectively) and the diameters of the arterioles were measured sequentially at baseline and after topical application of either mefenamic acid (MA, 20 mumol litre-1) or N omega-nitro-L-arginine (NNA, 300 mumol litre-1), inhibitors of prostaglandins and nitric oxide, respectively. In group E, baseline arteriolar diameters were significantly higher than those in the two other groups (P < 0.01). MA and NNA induced significant constriction in the three groups (P < 0.001). However, whereas constriction induced by NNA was similar in the three groups, constriction induced by MA was significantly higher in group E compared with groups P and T (P < 0.05). We conclude that diaphragmatic arteriolar diameters in rats were greater during etomidate than during thiopental or propofol anaesthesia. This phenomenon may be mediated by prostaglandins.

Anesthetics, Intravenous↗

PubMed1998

In vivo study of the effect of systemic hypoxia on leukocyte-endothelium interactions.

To evaluate the effect of systemic hypoxia on leukocyte-endothelium interactions in peripheral tissues, we studied by intravital microscopy leukocyte rolling velocity and adherence in venules of rat cremaster muscle. We examined the possible roles of changes in blood oxygenation, peripheral tissue oxygenation, changes in local shear rate, and the involvement of integrins. Six groups of rats submitted to either control normoxic conditions, or systemic hypoxia (PO2 = 51 mm Hg) associated with either low O2 tension of Krebs superfusing the muscle, high O2 tension of the Krebs superfusing the muscle, anti-lymphocyte function-associated antigen (LFA)-1beta antibody, pentoxifylline, or normoxic conditions associated with partial occlusion of the artery perfusing the muscle. We found that: (1) systemic moderate hypoxia resulting from purely respiratory disturbance even in the absence of local stop-flow phenomenon or circulatory shock can induce an increase in leukocyte adhesion and a decrease in leukocyte rolling velocity in the microcirculation of peripheral tissues; (2) to be present, this increase in leukocyte adhesion does not require tissue hypoxia of the peripheral tissue but the effect of systemic hypoxia on rolling velocity is prevented by tissue oxygenation; (3) this increase in leukocyte adhesion is mediated by CD11/CD18 integrins but is not due to changes in local shear rate.

Animals↗