[Noninvasive assessment of pulmonary hypertension using pulsed Doppler sonography in adult patients with cystic fibrosis].
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Adolescent↗
Biomedical subjects
O C Burghuber
Publications and source records attributed to O C Burghuber.
Nifedipine attenuates acute hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease.
The calcium channel blocker nifedipine was administered to patients with chronic obstructive pulmonary disease (COPD) to determine its efficiency as a pulmonary vasodilator. Since nifedipine has been shown to decrease elevated pulmonary artery pressures in patients with hypoxic pulmonary hypertension, we hypothesized that nifedipine would attenuate acute hypoxic pulmonary vasoconstriction in patients without pulmonary hypertension. We studied 11 clinically stable patients with mild to moderate COPD and normal pulmonary artery pressures using a randomized single-blind cross-over design. The patients were studied before and after nifedipine (20 mg) or placebo, given sublingually, at room air and subsequently during inhalation of a hypoxic gas mixture containing 13% O2, 5% CO2 and 72% N2. During normoxia, nifedipine significantly increased cardiac index from 4.2 +/- 0.3 to 4.9 +/- 0.5 liters/min/m2 (p less than 0.05) and the coefficient of oxygen delivery from 4.15 +/- 0.3 to 4.91 +/- 0.5 (p less than 0.05), whereas placebo treatment did not. During isocapnic hypoxia, a significant increase in mean pulmonary artery pressure (from 15.7 +/- 0.7 to 24.4 +/- 1.2 mm Hg; p less than 0.005) and mean pulmonary vascular resistance index (from 2.6 +/- 0.3 to 4.2 +/- 0.5 mm Hg; p less than 0.005) could be observed. Pretreatment with nifedipine significantly attenuated the hypoxia-induced increase in mean pulmonary artery pressure by 53% and of the mean pulmonary vascular resistance index by 50%. This was accomplished without significant changes in systemic arterial pressure and in the systemic vascular resistance index. Thus, nifedipine acutely dilates the constricted vascular bed associated with hypoxia in these patients with COPD.
Aged↗
[Value of calcitonin and 6-oxo-prostaglandin Fl alpha in the differentiation of lung cancers].
Plasma calcitonin and 6-oxo-Prostaglandin-F1 alpha (6-oxo-PGF1 alpha), one of the stable metabolite of prostacyclin, were determined in patients with malignant and non-malignant diseases of the lung. 11 out of 14 patients with small cell carcinoma and only 3 out of 17 patients with other histological types of lung cancer had abnormally elevated plasma calcitonin levels. 6-oxo-PGF1 alpha levels were significantly higher in patients with different types of lung cancer, compared to a control group with non-malignant lung disease. Combining the results of calcitonin and 6-oxo-PGF1 alpha measurements led to improved specificity and efficiency for the correct differentiation between small cell and non-small cell carcinoma of the lung; the predictive value for the diagnosis of small cell carcinoma approached 90%.
6-Ketoprostaglandin F1 alpha↗
[Peripheral and right atrial plasma levels of atrial natriuretic peptide and their relation to mean atrial pressure].
Atrial myocytes produce natriuretic and vasodilating peptides. Animal experiments have shown that atrial natriuretic peptide (ANP) is released after stretching the atria and drained via the coronary vein effluent. In this study ANP-plasma levels were measured in 14 patients. Blood samples were simultaneously collected from the right atrial cavum and from an antecubital vein. In the right atrial samples, ANP-plasma concentrations were significantly higher than in samples drawn from a peripheral vein (140.3 +/- 114.8 pg/ml vs 96.9 +/- 69.2 pg/ml; p less than 0.05), but a significant linear correlation was found between both values (r = 0.88; p less than 0.001). In patients with elevated atrial pressures significantly higher ANP-levels could be detected than in patients with normal atrial pressures (204 +/- 115 pg/ml vs 55.3 +/- 18.5 pg/ml; p less than 0.05). Mean right atrial pressure correlated to ANP-levels in right atrial blood (r = 0.79; p less than 0.001) as well as to ANP-levels in peripheral blood (r = 0.68; p less than 0.01). These results indicate that higher ANP plasma levels can be measured in samples drawn from a site close to ANP production. On the other hand, atrial pressure might influence the amount of circulating ANP.
Adolescent↗
[Radiologic detection of pulmonary artery hypertension].
In 43 patients with obstructive and restrictive lung disease a catheterisation of the right heart with measurement of pulmonary artery pressure was performed. In a retrospective study several radiological parameters of pulmonary hypertension were evaluated on the chest radiographs of these patients. Considering those parameters on the p.a. and lateral chest radiograph, the diagnosis of pulmonary hypertension in patients with elevated pulmonary artery pressure at rest can be made with great accuracy. When pulmonary artery pressure is elevated only during exercise, the accuracy of radiological diagnosis is much lower.
Female↗
Hydrogen peroxide induced pulmonary vasoconstriction in isolated rat lungs is attenuated by U60,257, a leucotriene synthesis blocker.
Reactive oxygen metabolites cause pulmonary vasoconstriction and activate arachidonic acid metabolism. We proposed that hydrogen peroxide, generated enzymatically in an insolated rat lung model, would cause vasoconstriction which was independent of circulating cells, but dependent on activation of the arachidonic acid cascade. Although hydrogen peroxide caused an increase in lung effluent thromboxane B2 concentration, indomethacin did not inhibit hydrogen peroxide induced vasoconstriction. In order to test the hypothesis that hydrogen peroxide activates the 5-lipoxygenase pathway, lung effluents were analyzed for 5-hydroxy-eicosatetranoic acid (5-HETE) using a sensitive, highly specific mass spectrometer technique. Glucose oxidase increased the 5-HEFE effluent concentrations and this was prevented by U60,257. We therefore conclude that hydrogen peroxide stimulates the 5-lipoxygenase pathway and that substances derived from this pathway are at least in part responsible for the hydrogen peroxide induced vasoconstriction in isolated rat lungs.
Animals↗
[Inhibition of hypoxic pulmonary vasoconstriction by leukotriene blockade].
The mechanism of hypoxic pulmonary vasoconstriction is still unclear. Since leukotrienes are pulmonary vasoconstrictors and lung cells are able to produce leukotrienes, it has been proposed that leukotrienes are mediators of hypoxic pulmonary vasoconstriction and then inhibition of their synthesis should block hypoxic pressure responses. In order to test this hypothesis we investigated whether diethylcarbamazine (DEC), a known leukotriene synthesis blocker, blocks hypoxic pulmonary vasoconstriction in isolated rat lungs. DEC blocked ongoing and subsequent hypoxic pressure responses in a relatively specific and dose-dependent fashion. We therefore extended our observations to awake rats and found that DEC reversibly inhibited acute hypoxic pulmonary vasoconstriction. Furthermore, pulmonary hypertension and right ventricular hypertrophy in rats exposed to chronic hypobaric hypoxia could be prevented by DEC treatment. From these data we conclude that DEC inhibits both acute and chronic hypoxic pulmonary vasoconstriction. Thus, leukotrienes could be important mediators of hypoxic pulmonary vasoconstriction.
Angiotensin II↗
Inhibition of acetylcholine-induced bronchoconstriction in asthmatics by nifedipine.
The calcium-dependent constriction of bronchial smooth muscle cells and release of mediators derived from mast cells is important in the pathophysiology of asthma. We hypothesized that nifedipine, a slow calcium channel blocker, would inhibit or attenuate acetylcholine-induced bronchoconstriction in asthmatics. Because one consequence of mast cell activation is the release of platelet-activating factor, we wondered whether thromboxane levels would be increased during acute bronchial constriction in asthmatics. Bronchoconstriction was induced in 8 asthmatics (6 men, 2 women) by acetylcholine; each subject was pretreated either with placebo or nifedipine (20 mg sublingually) on 2 separate days. Vital capacity, forced expiratory volume in 1 s, peak expiratory flow rates and oscillatory resistance were measured prior to and after the intake of placebo or nifedipine as well as after an acetylcholine challenge. Pretreatment with nifedipine significantly attenuated acetylcholine-induced changes in all four lung function parameters studied, but did not significantly influence the increase in thromboxane B2 plasma concentrations observed after the acetylcholine challenge. From these data we conclude that nifedipine inhibits the acetylcholine-induced bronchoconstriction in asthmatics. This effect may be either a direct action on bronchial smooth muscle or may be due to the inhibition of mediators other than thromboxane.
Acetylcholine↗
Platelet sensitivity to prostacyclin in smokers and non-smokers.
Platelet activating effect of cigarette smoking appears to be important in the development of atherosclerosis. We previously demonstrated a reduced sensitivity of platelets to exogenous prostacyclin (PGI2) in vitro from patients with proven atherosclerotic disease, indicating a possible role of altered platelet function in the development of atherosclerosis. We now hypothesize that cigarette smoking might be an important cause of altered platelet sensitivity to PGI2 observed in patients with atherosclerosis. To test this hypothesis, the response of platelets to exogenous PGI2 was tested in chronic smokers and non-smokers, prior to and after smoking two cigarettes (active smoking) and prior to and after exposure to a tobacco smoke-contaminated atmosphere (passive smoking). This study indicates that platelets of chronic smokers are less sensitive to exogenous PGI2 than platelets of non-smokers. In addition, active as well as passive smoking decreases platelet sensitivity to PGI2 in non-smokers, whereas chronic smokers exhibit no further decline. We conclude that decreased platelet sensitivity to PGI2 might be an important contributing factor to the altered platelet function observed in patients with atherosclerosis.
Adult↗
[Immune thrombocytopenia in Hodgkin's disease].
Thrombocytopenic purpura of the idiopathic thrombocytopenic purpura (ITP) type is an unusual and poorly documented complication of Hodgkin's disease. In an eight year period, three patients out of 140 with Hodgkin's disease developed thrombocytopenia; two of them presented a clinical picture undistinguishable from classic ITP. In both platelet antibody could be demonstrated. The third patient developed thrombocytopenia during an acute exacerbation of the underlying disease. Successful therapy of thrombocytopenia was achieved by methylprednisolone alone in one case and by cyclophosphamide in combination with methylprednisolone in the other two cases. These case reports demonstrate again that thrombocytopenia in Hodgkin's disease take place in active phases as well as in periods of complete remission; in the latter thrombocytopenia may reflect a part of immunological imbalance closely related to the pathophysiological background of Hodgkin's disease.
Adult↗
Leukotriene inhibitors attenuate rat lung injury induced by hydrogen peroxide.
It is known that reactive oxygen species cause lung injury in association with activation of arachidonate metabolism. Because metabolites of the cyclooxygenase pathway do not appear to mediate the injury, we considered that the 5-lipoxygenase pathway might be activated and that inhibition of the pathway could interfere with the development of the injury. Thus, we sought to induce an oxidant lung injury and to prevent such injury by inhibiting lipoxygenase pathway or by blocking leukotriene action. In isolated rat lungs, glucose oxidase added to a glucose-containing, cell-free perfusate was used to produce the injurious oxygen species. Lung edema occurred and increased with increasing oxygen tension in the inspired air. Light microscopy of the lung showed perivascular fluid cuffs, and electron microscopy showed endothelial cell damage. Measurements in the lung effluent showed that concentrations of 5-hydroxyeicosatetraenoic acid (5-HETE) and of cyclooxygenase metabolites increased after glucose oxidase administration; BW 755C, U60,257, and FPL 55712 inhibited the glucose-oxidase-induced lung edema. And U60,257 also inhibited the glucose-oxidase-induced increase in 5-HETE without concomitant inhibition of cyclooxygenase metabolites. Thus, glucose oxidase via generation of active oxygen species stimulated the lung 5-lipoxygenase pathway, and inhibitors of 5-lipoxygenase protected against the oxidant lung injury. Further, in these experiments, the injury occurred in the absence of circulating blood cells and was augmented by increasing the inspired oxygen concentration.
Animals↗
Pulmonary and antiaggregatory effects of prostacyclin after inhalation and intravenous infusion.
Prostacyclin (PGI2) was administered by inhalation (50 micrograms/min) and intravenous infusion (15 ng/kg/min) in 5 healthy male volunteers. Irrespective of the route of administration this substance was shown to have no effects on respiratory indices studied, whereas a significant inhibition of ADP-induced platelet aggregation and a fall in vascular resistance could be demonstrated. Mainly because of the latter action it is suggested that PGI2, or a stable synthetic analogue, might become a potent drug in various pathological conditions, in which hypertension of various causes is a problem.
Adult↗
Efficacy of cyclosporin A in systemic sclerosis.
In this open pilot study, the potential therapeutic efficacy of Cyclosporin A (CsA) in systemic sclerosis (scleroderma) was investigated. Eight patients with severe scleroderma (skin manifestation and at least three organ manifestations such as pulmonary, intestinal, cardiac, renal, and severe hypertension) were included in the study. CsA administration was started at a dose of 5 mg per kg body weight per day and then, to obtain whole blood levels of 300-500 ng/ml, adjusted to a mean dosage of 4.3 mg/kg/day. Therapeutic effects were evaluated by monitoring the measures of cutaneous, pulmonary, cardiac, gastrointestinal, and renal involvement as well as laboratory parameters. After 6 to 12 months of CsA-administration, cutaneous abnormalities improved in seven, arterial oxygen tension slightly increased in four, pulmonary hypertension decreased in five, and smooth muscle esophageal contraction amplitudes improved in three patients. However, the disease progressed in one patient. No serious side effects were observed, and occurring renal side effects were mild. Taken together, these observations indicate that CsA administration may be effective mainly in the skin involvement, but also in some organ manifestations of scleroderma. The results of this pilot investigation therefore indicate that a controlled study of the efficacy of CsA in scleroderma is needed and ought to be performed.
Adult↗