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Biomedical subjects

A F Junod

Publications and source records attributed to A F Junod.

At least 91 records · Page 5Linked to original sources
PubMed1985

Effects of atelectasis and vascular occlusion on the simultaneous measurement of serotonin and propranolol pulmonary extraction in dogs.

To test the relative sensitivity of serotonin and propranolol pulmonary extraction measurements to changes in pulmonary vascular surface, we sequentially subjected anaesthetized dogs to left upper lobe atelectasis, left lung atelectasis and left pulmonary artery occlusion. We used a triple-indicator dilution technique to simultaneously measure the pulmonary extraction of serotonin and propranolol. After an initial series of measurements, dogs received dopamine and dextran to slightly increase pulmonary artery pressure and prevent further recruitment of capillaries. Left upper lobe atelectasis did not modify the pulmonary extraction of serotonin and propranolol. Left lung atelectasis provoked a reduction in the serotonin extraction ratio by only 4%, whereas the propranolol extraction ratio decreased by 13%. After left pulmonary artery occlusion, propranolol and serotonin extraction ratios decreased by 16% and 5% respectively. We conclude that the pulmonary extraction of propranolol is more sensitive to a decrease in pulmonary vascular surface than that of serotonin.

Animals↗
PubMed1985

Effects of hyperoxia on DNA synthesis in cultured porcine aortic endothelial cells.

The mode of action of hyperoxia on the inhibition of DNA synthesis from thymidine (dThd) was studied in primary cultures of porcine aortic endothelial cells (EC) at confluence. A significant effect of hyperoxia on dThd uptake was detected only after a 48-h exposure to 95% O2. On the other hand, decrease in dThd kinase activity was already observed after a 12-h exposure, and the time course of its reduction followed closely that of the inhibition of dThd incorporation into DNA. The incorporation of dThd triphosphate into DNA in permeabilized EC was unaffected by hyperoxia. Determination of DNA alpha- and beta-polymerase activities showed that hyperoxia reduced the activity of the alpha-polymerase and increased that of the beta-polymerase. We conclude that most of the O2 effects on DNA synthesis from dThd can be attributed to dThd kinase inhibition. The increased activity of DNA beta-polymerase, an enzyme involved in DNA repair, also supports the view that hyperoxia could damage DNA.

Animals↗
PubMed1985

Simultaneous measurement of serotonin and propranolol pulmonary extraction in patients after extracorporeal circulation and surgery.

To evaluate the use of markers of pulmonary endothelial cell function in humans, we simultaneously measured the pulmonary extraction of serotonin (SER) and propranolol (PROP) in patients before and after extracorporeal circulation (ECC) for coronary bypass surgery. No change was seen in SER extraction ratio after anesthesia, ECC, and surgery. Twenty-four hours after ECC and surgery, PROP extraction ratio was decreased by 11%. It remained low for as long as 5 days thereafter. A similar drop in PROP extraction was found in 6 patients 24 h after ilioaortic bypass surgery, without ECC (from 81 to 66%, p less than 0.01). Treatment of 11 other patients with a 30-min period of continuous positive airway pressure (CPAP), 24 to 48 h after ECC, resulted in a significant increase in PROP extraction ratio from 61 to 67% (p less than 0.01). Measurement of PROP extraction appears to be more sensitive than that of SER to lung changes related to postoperative atelectasis.

Adult↗
PubMed1985

Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome.

Because injury to the pulmonary vascular endothelium is associated with the development of the adult respiratory distress syndrome (ARDS), we assessed the metabolic function of pulmonary endothelial cells by the measurements of the first-pass pulmonary extraction of [14C]serotonin and [3H]propranolol in 15 patients with ARDS and 15 patients at risk for developing ARDS. Serotonin extraction ratio was lower in patients with ARDS (0.85 +/- 0.10, mean +/- SD) than in patients at risk (0.91 +/- 0.04) (p less than 0.025), and both values were significantly reduced (p less than 0.005) when compared with a control group value (0.97 +/- 0.01). The decrease in serotonin extraction was correlated with the severity of ARDS (r = -0.67) (p less than 0.001) and with pulmonary function changes over time. Propranolol extraction ratio was decreased in patients at risk (0.66 +/- 0.11) (p less than 0.005) but not in patients with ARDS (0.75 +/- 0.11), when compared with those in the control group (0.81 +/- 0.03). Low values in patients at risk were restored to normal by continuous positive airway pressure breathing. We conclude that pulmonary extraction of serotonin, an index of pulmonary endothelial cell function, correlates with the severity of ARDS.

Adult↗
PubMed1985

Effect of variable glutathione peroxidase activity on H2O2-related cytotoxicity in cultured aortic endothelial cells.

Primary cultures of porcine aortic endothelial cells were used to assess the effects of O2 intermediates produced by 10-40 mU/ml xanthine oxidase (XO; +2 mM hypoxanthine) or 25-100 mU/ml glucose oxidase (GO; +5 mM glucose). A 60-min incubation in the presence of the enzyme systems resulted in a dose-dependent toxic effect with evidence of cytolysis (increased LDH release) and cell loss (decrease in DNA and protein content), when these indexes were measured 24 hr after completion of the enzyme reaction. Decreased [3H]thymidine incorporation into DNA was the most sensitive index of cell dysfunction for both enzyme systems. The effects of various scavengers and enzymes indicated that H2O2 was the main O2 intermediate involved in the cytotoxicity resulting from the XO-hypoxanthine reaction. Increased glutathione peroxidase activity associated with the addition of 2 X 10(-7) M selenomethionine to culture medium had a partial protective effect which could be related to an increased rate of H2O2 degradation. Evidence for increased DNA synthesis after injury was found in cells previously exposed to XO-hypoxanthine, the degree of increase in [3H]thymidine incorporation being dependent on the intensity of the initial cytotoxicity. Cultured endothelial cells provide a useful tool to evaluate the role of O2 intermediates in endothelial cell injury, to test the effects of protective agents, and to study the repair process.

Animals↗
PubMed1985

Direct toxic effects of paraquat and oxygen on cultured endothelial cells.

Paraquat (PQ) is a herbicide known to generate O2 radicals and to injure lung epithelial cells, leading eventually to pulmonary fibrosis. To test for the possible existence of a direct cytotoxic action of PQ on endothelial cells, we have studied, for up to 5 days, the action of 10(-6) to 10(-4) M PQ on primary cultures of pig aortic endothelial cells and compared these effects to those obtained with exposure to 95% O2-5% CO2. The decrease in DNA and protein content of Petri dishes and the increase in lactate dehydrogenase release were found to depend on PQ concentration and the duration of exposure to PQ. The toxic effects of hyperoxia were intermediate, ranging between those obtained with 10(-5) and 10(-4) M PQ. Hyperoxia and 10(-4) M PQ produced a similar marked inhibition of DNA synthesis after a 1-day period of exposure. Combined exposure to both PQ and hyperoxia resulted in changes comparable to those obtained with hyperoxia alone (decrease in protein and DNA content) or PQ alone (lactate dehydrogenase release). Additive effects were seen only for the inhibition of DNA synthesis. The selenomethionine-related increase in glutathione peroxidase activity had a protective effect against hyperoxia-induced lactate dehydrogenase release but not against PQ induced cytolysis. Finally, shorter exposures to O2 and PQ revealed the existence of a trend toward recovery only for cells exposed to hyperoxia. The prolonged toxic action of PQ could not be related to PQ accumulation and storage by endothelial cells. These studies indicate that PQ can exert a direct, dose-dependent, and prolonged cytotoxic effect on cultured endothelial cells.

Animals↗
PubMed1985

Comparative effects of acute O2 breathing and terbutaline in patients with chronic obstructive pulmonary disease. A combined hemodynamic and radionuclide study.

The acute effects of terbutaline (T) and breathing 100% O2 (O2) on gas exchange, pulmonary hemodynamics and radionuclide angiography were evaluated in 15 patients with severe chronic obstructive pulmonary disease (COPD). O2 breathing resulted in a decrease in mean pulmonary artery pressure (PAP) and cardiac index (CI) without changing pulmonary vascular resistance index (PVRI) or right and left ventricular ejection fractions (RVEF, LVEF). On the other hand, T administration was followed by a decrease in PVRI, an increase in CI, RVEF and LVEF. These effects of T were maintained during exercise. Although RVEF was inversely correlated with basal levels of PAP or PVRI, acute changes in pulmonary hemodynamics were not correlated with significant changes in RVEF. These results suggest that T may be useful in the treatment of patients with COPD prone to develop cor pulmonale. However, the long-term benefit of this treatment remains to be established.

Aged↗
PubMed1984

[Respiratory problems during sleep].

Continuous recording of numerous physiological variables during the night has led to the discovery of various respiratory disorders occurring during sleep. The most important are: 1. central apneas, defined by excessive frequency of respiratory arrests of excessive duration, 2. obstructive apneas, characterized by marked obstruction at the level of the oropharynx with persistence of respiratory movements, 3. episodes of marked nocturnal hypoxemia, without apnea, in certain patients with chronic obstructive lung disease. The pathophysiology, clinical picture and possible therapeutic resources are analyzed for each of the respiratory disorders occurring during sleep.

Diagnosis, Differential↗
PubMed1984

Ventilatory response to bronchospasm induced by methylcholine and histamine in man.

In 9 normal subjects, we compared mouth occlusion pressure (P0.1) and breathing pattern in bronchospasm of the same magnitude induced by inhalation of acetyl-beta-methylcholine (M) and histamine phosphate (H). The measurements were performed on two different days, in a single blind randomized crossover design, under basal conditions first, then after control inhalation of isotonic buffered saline and finally after inhalation of M or H. For a same mean decrease in FEV1 (+/- SD) by 22.2% (+/- 7.2) after M and 22.3% (+/- 9.4) after H (P less than 0.001), the increases in P0.1 were similar (P less than 0.01 for both drugs) and were correlated to the magnitude of the bronchospasm (r = 0.775, P less than 0.01 for M; r = 0.692, P less than 0.05 for H). However, the minute ventilation and breathing pattern parameters did not differ from each other and from basal or control conditions. Thus, although we can assume that both drugs have different effects on vagal airway receptors, they induce the same respiratory response. We conclude that only receptors indirectly stimulated via airway smooth muscle contraction contribute to the mediation of drive and breathing pattern in drug induced bronchospasm in humans.

Adult↗
PubMed1983

Effects of hyperoxia on biochemical indexes of pig aortic endothelial function.

To determine what biochemical indexes might be useful in measuring the endothelial response to hyperoxia in vitro we exposed endothelial cell monolayers (ECM) from pig aortas to either hyperoxic (95% O2:5% CO2, 1 atm) or control conditions (95% air:5% CO2) and made the following measurements: (a) DNA and protein contents remaining in the ECM; (b) lactate dehydrogenase (LDH) activity in the medium; (c) the net uptake of rubidium (Rb+), adenine, and adenosine; and (d) cellular ATP and medium lactate. Twelve hours of hyperoxic exposure did not cause significant changes. After 24 or 48 h of hyperoxia, DNA and protein contents were decreased; LDH activity and the protein-to-DNA ratio were increased; adenosine uptake was decreased per ECM but was unchanged when corrected for culture DNA and protein contents. Adenine uptake was unaltered as were cellular ATP content and medium lactate concentration. The net Rb+ uptake-to-DNA ratio was increased after 24 h but not after 48 h of hyperoxia. The extent of the DNA and LDH changes indicated that the cellular disturbance caused by hyperoxia was progressive from 12 to 48 h. Presence of superoxide dismutase (250 U/ml) prevented both the increase of LDH activity and the decrease of protein after 48 h but did not affect the decrease of DNA. These results suggest that the cells remaining in the ECM after hyperoxia have normal biochemical function and may represent a subpopulation of cells more resistant to oxygen toxicity than the damaged cells.

Adenine↗
PubMed1983

A comparison of adenine and some derivatives on pig isolated tracheal muscle.

We studied the muscle relaxation induced by adenine and several adenine derivatives in strips of tracheal smooth muscle from pigs; in addition their metabolism by the tissue was examined. Adenine relaxed tissue which was contracted by carbachol, histamine, or KCl. Adenine's potency was similar to that of adenosine and ATP (threshold about 4 X 10(-5)M). In tissues with carbachol-induced tone, the adenine effect differed from adenosine and ATP by being slower in onset and in 'washout' time. Furthermore, neither dipyridamole nor theophylline modified the response to adenine. The relationship was examined between pharmacological effects and the metabolism of [3H]-adenosine and [3H]-adenine. Both substrates were taken up by the tissue and converted to nucleotides, but relaxation correlated with nucleotide accumulation only in the case of [3H]-adenine. We conclude that the site and mechanism of adenine-induced relaxation is different from that of adenosine and ATP in porcine tracheal muscle.

Adenine↗
PubMed1983

Oxygen toxicity in cultured aortic endothelium: selenium-induced partial protective effect.

The time course of biochemical changes related to cell loss and damage during exposure to 95% O2 [DNA and protein content of dishes, lactate dehydrogenase (LDH) release] was studied in postconfluent endothelial cells isolated from pig aorta, cultured in standard medium and in medium supplemented with 2 X 10(-7) M selenomethionine (Se-Met). A fourfold increase in glutathione peroxidase (G-Px) was the only major enzymatic Se-related effect under both normoxic and hyperoxic conditions, the other antioxidant enzymes being little or not at all affected by this treatment. The addition of Se-Met had a clearcut protective action against the cytotoxic effect of O2 as shown by measurements of DNA and protein content of Petri dishes and of LDH release. On the other hand, the most sensitive O2-related effect, namely the decrease in [3H]thymidine incorporation into DNA, was not affected by Se-Met addition. These experiments suggest that some of the O2-related toxic effects (but not the inhibition of DNA synthesis) could be mediated by lipid peroxides, since they were, at least partly, prevented by a Se-Met-induced increase in G-Px activity.

Animals↗
PubMed1983

Ventilatory dysfunction resulting from bilateral anterolateral high cervical cordotomy. Dual beneficial effect of aminophylline.

Because of metastatic pain resistant to medical treatment after left pneumonectomy for squamous cell carcinoma, a 46-year-old patient underwent a bilateral cervical cordotomy at the C1-C2 anterolateral level, in two phases. The second intervention was followed by severe ventilatory problems requiring mechanical ventilation, and at a later stage, the implantation of a phrenic pacemaker on the right side. Analysis of the ventilatory pattern during spontaneous breathing and during phrenic pacing and measurement of the transdiaphragmatic pressure during phrenic nerve stimulation revealed the existence of a beneficial effect of aminophylline on both the regulation of ventilation and diaphragmatic contractility.

Aminophylline↗
PubMed1983

[Markers of cell populations in the lower lung].

Trends in basic research in thoracic medicine are increasingly orientated to biochemical and cellular studies. The need for "biochemical markers" as evidence of a particular type of cell is soon appreciated, both from a qualitative as well as quantitative viewpoint. The ideal criteria which these "markers" should possess (specificity for the organ and cell population and reflecting a well defined metabolic activity) are unfortunately rarely satisfied; the "marker" may be analysed in plasma or broncho-alveolar lavage liquid. Two examples are presented and the difficulties of their interpretation are discussed. First in relation to the determination of serum angiotensin converting enzyme activity and then elastolytic activity in the broncho-alveolar liquid. A good knowledge of basic biological phenomena is necessary to take full advantage of the information which can be obtained by measuring "markers" of activity or function of pulmonary cells.

Humans↗
PubMed1982

Effects of culture conditions and hyperoxia on antioxidant enzymes in pig pulmonary artery and aortic endothelium.

Because hyperoxia induces early injury to lung endothelial cells and since tolerance to hyperoxia is correlated with increased lung antioxidant enzyme activity, we measured superoxide dismutase, catalase and glutathione peroxidase in both fresh isolates and primary cultures of endothelial cells from pig pulmonary artery and aorta. Cultured endothelial cells were studied at confluency and up to 5 days thereafter under control or hyperoxic conditions. In both types of confluent cell, total and cyanide-insensitive superoxide dismutase increased when compared to fresh cells. The most conspicuous postconfluency change in both types of endothelial cell was a marked decrease in glutathione peroxidase, which could be prevented by the addition of selenomethionine to culture media. A 5-day exposure to hyperoxia resulted in a 2-fold increase in cyanide-insensitive superoxide dismutase in both aortic and pulmonary artery endothelial cells. In view of a similar decrease in DNA in both types of cells despite some differences in enzyme levels, oxygen cytotoxicity could not be related to a particular antioxidant enzyme profile.

Aerobiosis↗