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S Adnot

Publications and source records attributed to S Adnot.

At least 37 records · Page 2Linked to original sources
PubMed2001

Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension.

Structural remodelling of pulmonary vessels is an important feature of pulmonary hypertension (PH), which reflects distal artery muscularization and matrix remodelling. The matrix metalloproteinases (MMPs) are involved in extracellular matrix turnover and hence, in smooth muscle cell migration and endothelial cell migration and proliferation. Among the MMPs, gelatinases (MMP-2 and MMP-9) can degrade basement membrane components and promote cell proliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-2 activity, specific to pulmonary vessels. Increased MMP-2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonstrated upregulation of MMP-2 messenger ribonucleic acid. Immunolocalization showed MMP-2 throughout the pulmonary vasculature, from the trunk to the distal vessels, with strong staining of the intima, media and adventitia. MMP-2 was found in its active form and gelatinolytic activity was correlated to PH severity. Activity localization by in situ zymography corroborated with the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-2 activity is increased in pulmonary vessels during progression of pulmonary hypertension, probably as a result of involvement in the matrix turnover associated with vascular remodelling during pulmonary hypertension.

Animals↗
PubMed2001

Use of glass capillaries avoids the time changes in high blood PO(2) observed with plastic syringes.

STUDY OBJECTIVES: In adults, arterial blood samples are usually drawn using plastic syringes. In contrast to glass syringes, plastic syringes let oxygen diffuse through their wall. This results in PO(2) changes during storage, especially when PO(2) is high. An alternative to glass syringes is the Microsampler (Roche Diagnostics; Schaffhausen, Switzerland), a commercially available device consisting of a heparinized glass capillary fitted with a 26-gauge needle and used to collect arterial blood in the same way as a plastic syringe fitted with a needle. DESIGN: We evaluated the performance of the Roche Microsampler for storing arterial blood in view of PO(2) measurement, comparatively with glass and plastic syringes. Five approximate initial PO(2) levels (650, 400, 200, 130, and 80 mm Hg) and two storage temperatures (ambient temperature and 4 degrees C) were studied. SETTINGS: Bench study. RESULTS: Plastic syringes allowed reliable measurement of PO(2) values when initial PO(2) was too low to ensure complete hemoglobin oxygen saturation, but were associated with time-dependent underestimation of PO(2) at higher initial PO(2) values. No such underestimation occurred with the Roche Microsampler stored at 4 degrees C for up to 1 h for all PO(2) levels studied. CONCLUSION: The Roche Microsamplers appeared to be reliable devices in preventing oxygen diffusion.

Blood Specimen Collection↗
PubMed2001

Dexfenfluramine-associated changes in 5-hydroxytryptamine transporter expression and development of hypoxic pulmonary hypertension in rats.

The appetite suppressant dexfenfluramine, which inhibits neuronal 5-HT uptake and elevates plasma 5-HT levels, has been associated with an increase in the relative risk of developing primary pulmonary hypertension. 5-HT is a mitogen for pulmonary artery smooth muscle cells (PA-SMCs), an effect that depends upon activity of the 5-HT transporter (5-HTT). To investigate the relationship between dexfenfluramine and pulmonary hypertension, we examined 1) the effect of dexfenfluramine on 5-HT uptake by PA-SMCs and the mitogenic response of these cells to 5-HT, and 2) 5-HTT mRNA in lung tissue from normoxic and chronically hypoxic rats during and at discontinuation of a 4-week dexfenfluramine treatment (2 mg/kg/day). In cultured PA-SMCs, dexfenfluramine (10(-6) M) markedly reduced [3H]5-HT uptake and [3H]thymidine incorporation in response to 5-HT (10(-6) M). In lungs from rats exposed to 4-week hypoxia (10% O(2)), 5-HTT mRNA levels were higher than in normoxic rats (233.5 +/- 22.5 versus 121.8 +/- 4.8 amol/mg of RNA, P < 0.05), but were not affected by concomitant treatment with dexfenfluramine. One week after discontinuation of dexfenfluramine, 5-HTT mRNA levels increased substantially, this effect being additive with that of hypoxia (364.0 +/- 13.1 in hypoxic versus 164.2 +/- 10 amol/mg of RNA in normoxic rats). When exposure to 2 weeks of hypoxia followed discontinuation of a 4-week treatment, right ventricular hypertrophy was more severe and muscularization of distal pulmonary arteries more marked (P < 0.01) than in rats pretreated with the vehicle. These data show that, in rats, the increased 5-HTT expression that follows dexfenfluramine discontinuation promotes the development of hypoxic pulmonary hypertension.

Animals↗
PubMed2000

Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or doxycycline aggravates pulmonary hypertension in rats.

Chronic hypoxic pulmonary hypertension (PH) results from persistent vasoconstriction, excess muscularization, and extracellular matrix remodeling of pulmonary arteries. The matrix metalloproteinases (MMPs) are a family of proteinases implicated in extracellular matrix turnover and hence in smooth muscle and endothelial cell migration and proliferation. Because MMP expression and activity are increased in PH, we designed the present study to investigate whether inhibition of lung MMPs in rats subjected to chronic hypoxia (CH) contributes to or protects against vascular remodeling and PH. To achieve lung MMP inhibition, rats exposed to 10% O(2) for 15 days were treated with either doxycycline (20 mg/kg per day by gavage starting 2 days before and continuing throughout the CH period) or a single dose of recombinant adenovirus (Ad) for the human tissue inhibitors of metalloproteinases-1 (hTIMP-1) gene (Ad.hTIMP-1, 10(8) plaque-forming units given intratracheally 2 days before CH initiation). Control groups either received no treatment or were treated with an adenovirus containing no gene in the expression cassette (Ad.Null). Efficacy of hTIMP-1 gene transfer was assessed both by ELISA on bronchoalveolar lavages and by hTIMP-1 immunofluorescence on lung sections. MMP inhibition in lungs was evaluated by in situ zymography and gelatinolytic activity assessment using [(3)H]gelatin. Rats treated with either doxycycline or Ad.hTIMP-1 had higher pulmonary artery pressure and right heart ventricular hypertrophy more severe than their respective controls. Worsening of PH was associated with increased muscularization and periadventitial collagen accumulation in distal arteries. In conclusion, our study provides compelling evidence that MMPs play a pivotal role in protecting against pulmonary artery remodeling.

Animals↗
PubMed2000

Increased expression of gelatinases and alteration of basement membrane in rat soleus muscle following femoral artery ligation.

Acute severe muscle ischaemia is characterized by significant remodelling of basement membranes of myofibres. It was hypothesized that peripheral artery insufficiency is accompanied by similar muscle extracellular matrix (ECM) changes involving matrix metalloproteinase gelatinases. Using a model of femoral artery ligation, both gelatinase activity and basement membrane component degradation were studied in hindlimb skeletal muscles. SDS-PAGE zymography of muscle homogenates showed that acute moderate ischaemia was followed by a significant transient increase in expression of 72- and 92-kDa gelatinases during 48 h; the latter probably originated from inflammatory cells. In situ zymography showed that this increase occurred chiefly at the periphery of myofibres. Immunolocalization demonstrated 72-kDa gelatinase in interspaces and at the periphery of myofibres, and suggested that this enzyme may explain the gelatinolytic activities found by in situ zymography. Type IV collagen and laminin staining showed that the gelatinase expression increase correlated with dramatic basement membrane component alterations. Our data show that even moderate ischaemia results in significant muscle basement membrane remodelling due to matrix degrading enzymes matrix metalloproteinases (MMP) gelatinases.

Animals↗
PubMed2000

Molsidomine improves flow-dependent vasodilation in brachial arteries of patients with coronary artery disease.

Flow-mediated vasodilation (FMD) of human blood vessels is essential to adaptation and regulation of peripheral blood flow, and is mediated by endogenously produced nitric oxide. Endothelial function is impaired in many pathologic states, especially in coronary heart disease. We questioned in this study whether exogenous nitric oxide (NO) would restore endothelial dysfunction in peripheral arteries of patients with coronary artery disease (CAD). In a randomized double-blinded case-control assay, we used computerized A-mode ultrasonography to measure diastolic diameters of the brachial artery before and after hyperemia in two groups of 10 patients with CAD. Each group received orally either placebo or 12 mg molsidomine a day for 48 h. In the molsidomine group, FMD was improved with a 60% increase after the first intake of molsidomine, and the same trend was observed after the last intake, although less pronounced. Significant increase in diastolic diameter was observed after the last molsidomine intake, but not after the first one. Thus molsidomine has an early positive effect on FMD in addition to a delayed vasodilator effect. Improvement of endothelial dysfunction by molsidomine in patients with CAD may uncover new therapeutic perceptive in the use of nitrovasodilators.

Blood Flow Velocity↗
PubMed2000

Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell growth and permeability factor highly expressed in rodent alveolar epithelium after injury and repair. To investigate VEGF synthesis in human lung epithelial cells, we examined VEGF expression by cultured cells under basal conditions and after cytokine treatment or oxidative stress. Basal VEGF expression was detected in transformed human epithelial cell lines (A549 and 1HAEo-) and in primary human bronchial epithelial cells with RT-PCR, Western blot, and immunocytochemistry. Among the cytokines tested, only transforming growth factor-beta1 increased the levels of excreted VEGF(165) as measured by ELISA. Under hypoxia (0% O(2) for 24 h), the VEGF(165) level increased fivefold, and this effect was O(2) concentration dependent. VEGF concentrations in the medium of all the cell types studied reached values similar to those found in bronchoalveolar lavage fluids from normal patients. Endothelial cells (human umbilical vein endothelial cells) exposed to conditioned medium from primary bronchial epithelial cell cultures showed an increased growth rate, which was inhibited in the presence of a specific neutralizing antibody to VEGF. These results suggest that lung epithelial cells participate in the endothelial repair and angiogenesis that follow lung injury through the synthesis of VEGF.

Bronchoalveolar Lavage Fluid↗
PubMed2000

Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy.

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects. Platelet VEGF content was increased in patients with primary and secondary PH as compared with control subjects (518 +/- 89, 675 +/- 156, and 166 +/- 29 fg/10(5) platelets, respectively; p < 0.01), whereas platelet PDGF content was similar in the three groups (31 +/- 2, 36 +/- 4, and 33 +/- 3 pg/10(5) platelets, respectively; NS). Patients treated with a continuous prostacyclin infusion had a higher platelet VEGF but a similar platelet PDGF content as compared with untreated patients. Moderate increases in platelet VEGF and PDGF contents were observed in the CHLD patients. We conclude that patients with primary or secondary PH have an increase in platelet VEGF content, but not in platelet PDGF content, and that their platelet VEGF content increases further in response to prostacyclin infusion. We suggest that imbalance between platelet VEGF and PDGF is beneficial to patients with PH.

Adolescent↗
PubMed2000

Modulation of angiotensin II receptor expression during development and regression of hypoxic pulmonary hypertension.

Lung vessel muscularization during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II (Ang II) AT1 and AT2 receptors in this setting is not well known and has never been investigated during normoxia recovery. We determined both chronic hypoxia and normoxia recovery patterns of AT1 and AT2 expression and distal muscularization in the same lungs using in situ binding, reverse transcriptase/polymerase chain reaction, and histology. We also used an isolated perfused lung system to evaluate the vasotonic effects of AT1 and AT2 during chronic exposure to hypoxia with and without subsequent normoxia recovery. Hypoxia produced right ventricular hypertrophy of about 100% after 3 wk, which reversed with normoxia recovery. Hypoxia for 2 wk was associated with simultaneous increases (P<0.05) in AT1 and AT2 binding (16-fold and 18-fold, respectively) and in muscularized vessels in alveolar ducts (2. 8-fold) and walls (3.7-fold). An increase in AT2 messenger RNA (mRNA) (P<0.05) was also observed, whereas AT1 mRNA remained unchanged. After 3 wk of hypoxia, muscularization was at its peak, whereas all receptors and transcripts showed decreases (P<0.05 versus hypoxia 2 wk for AT1 mRNA), which became significant after 1 wk of normoxia recovery (P<0.05 versus hypoxia 2 wk). Significant reversal of muscularization (P<0.01) was found only after 3 wk of normoxia recovery in alveolar wall vessels. Finally, the AT1 antagonist losartan completely inhibited the vasopressor effect of Ang II in hypoxic and normoxia-restored lungs, whereas the AT2 agonist CGP42112A had no effect. Our data indicate that in lungs, chronic hypoxia-induced distal muscularization is associated with early and transient increases in AT2 and AT1 receptors probably owing to hypoxia- dependent transcriptional and post-transcriptional regulatory mechanisms, respectively. They also indicate that the vasotonic response to Ang II is mainly due to the AT1 subtype.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Adenovirus-mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats.

Chronic hypoxic pulmonary hypertension (PH) is associated with vasoconstriction and structural remodeling of pulmonary vessels including narrowing of the arterial lumen and loss of distal functional arteries. To test whether lung overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) is beneficial in hypoxic PH, recombinant adenovirus encoding the human VEGF 165 gene under the control of a cytomegalovirus promoter (Ad. VEGF) or control vector containing no gene in the expression cassette (Ad.Null) was administered intratracheally to rats. With Ad. VEGF (10(8) plaque-forming units [pfu]), VEGF protein was present in bronchoalveolar lavage fluid as early as 2 d and until 17 d after gene transfer, but was not detected in serum. Only small patchy areas of mononuclear cells without cell damage, edema, or hemorrhage were observed on lung histology with no significant change in lung permeability. In rats pretreated with Ad.VEGF (10(8) pfu) 2 d before a 2-wk exposure to hypoxia (10% O(2)), lower values versus Ad. Null-pretreated controls were found for pulmonary artery pressure (25 +/- 1 versus 30 +/- 2 mm Hg, P < 0.05), right ventricular over left ventricular-plus-septum weight (0.37 +/- 0.01 versus 0.47 +/- 0. 02, P < 0.001), normalized wall thickness of 50- to 200-microm vessels (P < 0.001), and muscularization of distal vessels (P < 0. 001). Pretreatment with Ad.VEGF (10(8) pfu) increased endothelial nitric oxide synthase activity in lung tissue and partially restored endothelium-dependent vasodilation in isolated lungs from chronically hypoxic rats, as assessed by improvement of ionophore A23187-induced vasodilation and attenuation of endothelin-1 (300 pmol)-induced vasoconstriction, an effect abolished in the presence of nitro-L-arginine methylester. We conclude that adenoviral-mediated VEGF overexpression in the lungs attenuates development of hypoxic PH, in part by protecting endothelium-dependent function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene.

Hypoxia is a well-recognized stimulus for pulmonary blood vessel remodeling and pulmonary hypertension development. One mechanism that may account for these effects is the direct action of hypoxia on the expression of specific genes involved in vascular smooth muscle cell (SMC) proliferation. Previous studies demonstrated that the serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) mediates the mitogenic activity of 5-HT in pulmonary vascular SMCs and is overexpressed during hypoxia. Thus, 5-HT-related mitogenic activity is increased during hypoxia. Here, we report that mice deficient for 5-HTT (5-HTT(-/-)) developed less hypoxic pulmonary hypertension and vascular remodeling than paired 5-HTT(+/+) controls. When maintained under normoxia, 5-HTT(-/-)-mutant mice had normal hemodynamic parameters, low blood 5-HT levels, deficient platelet 5-HT uptake, and unchanged blood levels of 5-hydroxyindoleacetic acid, a metabolite of 5-HT. After exposure to 10% O(2) for 2 or 5 weeks, the number and medial wall thickness of muscular pulmonary vessels were reduced in hypoxic 5-HTT(-/-) mice as compared with wild-type paired controls. Concomitantly, right ventricular systolic pressure was lower and right ventricle hypertrophy less marked in the mutant mice. This occurred despite potentiation of acute hypoxic pulmonary vasoconstriction in the 5-HTT(-/-) mice. These data further support a key role of 5-HTT in hypoxia-induced pulmonary vascular SMC proliferation and pulmonary hypertension.

Animals↗
PubMed2000

[Vasodilator effects of bradykinin on the resistive circulation of the forearm of coronary patients].

This study was undertaken to determine the vascular effects of bradykinin and its modes of action on the resistive circulation of the forearms of coronary patients and healthy volunteers. Two groups were studied: Group I comprising 8 coronary patients with normal left ventricular function and Group II with 8 healthy volunteers. The method of measurement of forearm blood flow was occlusive venous plethysmography with a mercury strain gauge. The vasodilatory response of the two groups to local arterial perfusion of acetylcholine (40 and 80 micrograms/min), bradykinin (10, 30, 100 pmoles/min), then the association of L-Ng-monomethyl-L-arginine (L-NMMA) at 8 microG/min, an inhibitor of the synthesis of nitric oxide, with acetylcholine and bradykinin. Five subjects of the control group received oral aspirin (250 mg/day) for one week before the study. Acetylcholine and bradykinin increased forearm flow in a dose-dependent manner but the increase was significantly less in coronary patients than in the healthy volunteers (p < 0.05). The L-NMMA inhibited the vasodilatory response to acetylcholine by about 40% in the two groups but had no significant effect on the vasodilatation induced by bradykinin. Aspirin had no effect on the vasodilatation induced by acetylcholine or bradykinin. These data show that the vasodilatory response to bradykinin is decreased in coronary patients and suggest that nitric oxide is not the second main messenger of bradykinin in the resistive circulation of the forearm.

Acetylcholine↗
PubMed1999

Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin.

-The increased delivery of serotonin (5-hydroxytryptamine, 5-HT) to the lung aggravates the development of hypoxia-induced pulmonary hypertension in rats, possibly through stimulation of the proliferation of pulmonary artery smooth muscle cells (PA-SMCs). In cultured rat PA-SMCs, 5-HT (10(-8) to 10(-6) mol/L) induced DNA synthesis and potentiated the mitogenic effect of platelet-derived growth factor-BB (10 ng/mL). This effect was dependent on the 5-HT transporter (5-HTT), since it was prevented by the 5-HTT inhibitors fluoxetine (10(-6) mol/L) and paroxetine (10(-7) mol/L), but it was unaltered by ketanserin (10(-6) mol/L), a 5-HT2A receptor antagonist. In PA-SMCs exposed to hypoxia, the levels of 5-HTT mRNA (measured by competitive reverse transcriptase-polymerase chain reaction) increased by 240% within 2 hours, followed by a 3-fold increase in the uptake of [3H]5-HT at 24 hours. Cotransfection of the cells with a construct of human 5-HTT promoter-luciferase gene reporter and of pCMV-beta-galactosidase gene allowed the demonstration that exposure of cells to hypoxia produced a 5.5-fold increase in luciferase activity, with no change in beta-galactosidase activity. The increased expression of 5-HTT in hypoxic cells was associated with a greater mitogenic response to 5-HT (10(-8) to 10(-6) mol/L) in the absence as well as in the presence of platelet-derived growth factor-BB. 5-HTT expression assessed by quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization in the lungs was found to predominate in the media of pulmonary artery, in which a marked increase was noted in rats that had been exposed to hypoxia for 15 days. These data show that in vitro and in vivo exposure to hypoxia induces, via a transcriptional mechanism, 5-HTT expression in PA-SMCs, and that this effect contributes to the stimulatory action of 5-HT on PA-SMC proliferation. In vivo expression of 5-HTT by PA-SMC may play a key role in serotonin-mediated pulmonary vascular remodeling.

Animals↗
PubMed1999

Expression of biologically active atrial natriuretic factor following intrahepatic injection of a replication-defective adenoviral vector in dogs.

Atrial natriuretic factor (ANF) is a potent natriuretic, diuretic, and vasoactive hormone produced and released by atrial cardiomyocytes. We investigated whether adenovirus-mediated ANF gene delivery to dogs leads to a sustained increase in circulating ANF levels resulting in long-lasting biological effects. An adenoviral vector containing the canine ANF cDNA under the control of the Rous sarcoma virus 3' long terminal repeat (AdRSV-ANF) was injected via the intrahepatic route to nonvaccinated 2-month-old dogs. In the first group of four dogs injected with AdRSV-ANF (10(10.2) TCID50), a short-lived increase in plasma ANF concentrations not associated with biological effects occurred 8-10 days after the injection, as compared with four control dogs injected with an adenovirus encoding a luciferase reporter gene (AdRSV-luc). In a second series of experiments, six dogs received AdRSV-ANF at a dose of 10(10) TCID50 and a replication-defective type 5 adenovirus harboring a modified VAI gene (Ad-VAr) at the same dose. Sustained increases in plasma ANF concentrations and urinary cGMP excretion starting on day 2 and persisting until day 20 were seen, as well as concomitant elevations in natriuresis and diuresis, a transient increase in cardiac output, and a delay in body weight gain, as compared with control dogs injected with AdRSV-luc/Ad-VAr. These results show that adenovirus-mediated ANF gene expression can lead to systemic biological effects in dogs, a finding of potential relevance for the treatment of cardiovascular diseases and sodium-retaining disorders.

Adenoviridae↗
PubMed1999

Induction of cardiac nitric oxide synthase 2 in rats exposed to chronic hypoxia.

Induction of nitric oxide synthase (NOS2, also designated as iNOS) in the heart is known to occur in response to various stimuli. It is not known, however, whether in vivo hypoxia leads to cardiac NOS2 induction. We thus investigated the effects of normobaric hypoxia (10% O(2)for 8, 15 and 21 days) on NOS2 protein expression and enzyme activity in rat right ventricle (RV) and left ventricle (LV). Chronic hypoxia induced RV hypertrophy: the RV weight to body weight ratio was increased by 45% upon 15 days of exposure, with no change thereafter and no change in left ventricular (LV) weight. Treatment of hypoxic rats with l -NAME for 1 month decreased pulmonary artery pressure and RV hypertrophy compared to hypoxic non-treated rats. NOS2 activity detected by [(3)H]l -arginine to [(3)H]l -citrulline conversion increased in RV during hypoxia, with a maximum at 15 days (+161% of control rats P<0.05), whereas it increased less (by 60%) in LV. In parallel, after 15 days of hypoxia there was a three-fold increase in NOS2 protein abundance detected by Western blotting using an isoform-specific antibody in the RVs (two-fold increase in the LV). Immunochemistry with the specific antibody demonstrated the expression in cardiomyocytes isolated from both ventricles of normoxic and hypoxic rats. Protein kinase C (PKC) content and activity was unchanged in LV of hypoxic rats, but increased in RV as compared with normoxic rats. These results clearly show that, in the heart, NOS2 is upregulated by hypoxia with an expression in cardiomyocytes of both ventricles. In addition, NOS2 is more inducible in the right hypertrophied ventricle than in the left non-hypertrophied hypoxic ventricle.

Amino Acid Sequence↗
PubMed1999

Accuracy of the i-STAT bedside blood gas analyser.

The performance of the i-STAT portable clinical analyser for measuring blood gases and pH was evaluated with reference to a conventional blood gas analyser (ABL520 Radiometer). Ninety-two samples from the routine blood gas analysis laboratory were chosen according to a wide distribution of partial pressure of carbon dioxide (Pa,CO2), partial pressure oxygen (Pa,O2) and pH and then analysed. All measurements were performed in duplicate by trained technicians from the central hospital laboratory. Differences between duplicate measurements were computed for Pa,CO2: (1.2 versus 0.4%), Pa,O2 (1.7 versus 1.1%) and pH (0.06 versus 0.02%), for the i-STAT and ABL520, respectively. pH and Pa,CO2 values measured with the i-STAT were very close to those obtained with the ABL520, the difference (mean+/-SD) being 0.006+/-0.018 and -0.13+/-0.17 kPa, respectively. Statistical analysis showed that the differences between analysers did not depend on values of pH or Pa,CO2. The performance of the analysers depended on the level of PO2. Below 15 kPa (n=48), the two systems gave nearly identical values, the mean difference was 0.01+/-0.37 kPa. Between 16 and 55 kPa (n=44), there was a systematic but small (-0.69+/-0.67 kPa) underestimation of Pa,O2 measured with the i-STAT (p<10(-8)). In conclusion, this study shows that blood gas analysis using the i-STAT portable device is comparable with that performed by a conventional laboratory blood gas analyser.

Blood Gas Analysis↗
PubMed1999

Local gene delivery within the media of rabbit iliac arteries by using the infiltrator intramural delivery device.

Percutaneous transluminal angioplasty continues to be limited by restenosis. Prevention of restenosis is now focusing on local delivery of therapeutic agents, such as proliferation-inhibiting genes, directly to the site of arterial injury. We evaluated use of the Infiltrator catheter (IVT, San Diego, CA. U.S.A.) for gene delivery within the arterial media. The goals of our study were to evaluate the histologic effects of the injection and the suitability of the Infiltrator catheter for local delivery of viral therapy. We injected the femoral arteries of 21 New Zealand White rabbits. Six animals were used for an evaluation of the intramural distribution of dextran/rhodamine injected via the Infiltrator catheter. In seven animals, injection site histology and in vitro vasoreactivity were studied after an injection of saline. In the remaining eight animals, a replication-deficient adenovirus encoding for the firefly luciferase gene (Ad RSVLuc) was injected, and luciferase activity was quantified 3 and 8 days later. After injection via the Infiltrator catheter, the fluorescent tracer was distributed throughout the entire circumference and width of the arteries. Histologic examination showed minimal damage with partial endothelial abrasion and disruption of the internal elastic lamina confined to the penetration sites. In vitro endothelium-dependent vasodilation was present at a reduced level after injection via the Infiltrator (maximal endothelium-dependent acetylcholine-induced relaxation, 51.5 +/- 7.4% vs. 23.8 +/- 14.6%; p < 0.05). Significant luciferase expression was found in all the arteries, with a significant increase from day 3 to day 8 (5,392.5 +/- 2,300 vs. 2,012 +/- 471 cpm/mg; p < 0.05). These data obtained in a rabbit iliac artery model show that the Infiltrator catheter is an efficient and safe local intramural delivery device that provides significant transgene expression in the arterial wall without causing significant structural damage.

Adenoviridae↗