The pulmonary blood volume (Q) can be measured by dye injection in the pulmonary artery (PA) and in the left atrium (LA) and by sampling in the brachial artery (double injection - single sampling method). We propose to replace the injection in the LA, for which a left heart catheterization is needed, by a pulmonary wedge injection (PW). No significant difference was found between the first and the second method in twenty-four measurements in six anesthetized and artificially ventilated dogs kept in steady hemodynamic state : QPW (1) equals 0.009 + 1.106 QLA (r equals 0.935). The results are independent of the capillary injection site. In man, the indirect validation was made by unilateral occlusion of a main pulmonary artery, allowing blood volume measurement of the occluded lung by two methods, one of them independent of the "capillary" injection. The results of both methods are comparable and highly correlated (r equals 0.86). The range of the values of pulmonary blood volume in sixteen normal supine subjects, at rest, was similar to that of other authors, whichever the technique they used (394 plus or minus 114 ml, 268 plus or minus 59 ml m-2). The reproducibility of the results was comparable. In five subjects, pulmonary blood volume did not change during a moderate muscular excerise in the supine position (57 watts). The pulmonary wedge injection in man can replace the LA injection of the double injection - single sampling method, without loss of precision nor effect on reproducibility.

Animals↗

PubMedDate not supplied

Best mode of expression of acute reversibility of airway obstruction in patients with asthma: application to a new beta-2 agonist, RU 42 173.

Lung function tests must distinguish a true drug-induced bronchial response from changes not related to the drug itself, mainly due to intra-individual variability. We compared the variability and ability to detect true drug-induced bronchodilation of 3 modes of expression of the increase in forced expiratory volume in 1 second (delta FEV1) following administration of a 0.25 mg single oral dose of RU 42 173, a new beta 2-agonist. The study was performed in 12 patients with reversible obstructive asthma in a double-blind, crossover, placebo-controlled, randomized manner. The variability of each index was assessed by calculating the coefficient of variation (SD/mean). True drug-induced bronchodilation was assessed by calculating the F value of each index corresponding to the ratio of between-treatment to within-group differences. Three modes of expression of delta FEV1 were compared: delta FEV1 (L) = the absolute increase in FEV1, delta FEV1 (% baseline) and delta FEV1 (% predicted) where delta FEV1 (L) is divided by baseline FEV1 or predicted FEV1, respectively. A statistically significant increase in FEV1 was found up to respectively 3, 2 and 4 hours after dosing when using delta FEV1 (L), delta FEV1 (% baseline) and delta FEV1 (% predicted). The highest F value was obtained for delta FEV1 (% predicted). The coefficient of variation was lower with delta FEV1 (% predicted) than delta FEV1 (L) and delta FEV1 (% baseline). In conclusion, RU 42 173 showed a bronchodilating effect which appears to be clinically relevant. delta FEV1 (% predicted) was to be the least variable and most powerful index and should be preferred to delta FEV1 (L) and even more to delta FEV1 (% baseline) to assess the acute airway response to a bronchodilator drug.

Adrenergic beta-Agonists↗

PubMedDate not supplied

[Non-prostanoid endothelium-derived factors. Physiologic roles and possible implications in cardiovascular pathology].

Non prostanoid endothelium-derived relaxing and contracting factors (EDRF and EDCF, respectively) are released by endothelial cells and act on the underlying vascular smooth muscle. It is now established that EDRF is nitric oxide (NO), whereas EDCF has been recently identified as a 21 residue peptide, called endothelin. However, circumstantial evidence suggests that there may be more than one EDRF and/or EDCF. EDRF (NO) induces relaxation of the underlying vascular smooth muscle by enhancing intracellular level of cyclic guanosine monophosphate. The mechanisms of action of endothelin are still to be defined. It seems however that influx of extracellular calcium may partly account for its action. Although important findings have been made recently, most of the hypotheseses, at our current stage of knowledge, about the respective roles of EDRF and EDCF in disease have still to be proved. However, it is preferable from now to think in terms of balance (or imbalance) between these two factors which, probably, have both a fundamental role and very likely interact with each other in maintaining and regulating vascular tone in man.

Animals↗

PubMedDate not supplied

[Gamma function extrapolation of dilution curves for pulmonary blood volume determination in chronic bronchitis (author's transl)].

The risk of incorporating inapparent recirculation under the extrapolated downslope of dye dilution curves is greater with exponential than gamma function extrapolation since the latter makes use of ascending and early descending limbs of the curve. Extrapolation of a true gamma function is not affected by the level at which extrapolation begins. With curves obtained in eight normal subjects, cardiac output (phi) was comparable by exponential and gamma extrapolation if the latter began between 75 and 55% of the peak concentration (Cmax.). phi was underestimated or overestimated according to whether extrapolation began higher or lower than the above limits. Therefore, experimental curves were not true gamma functions. However, the level at which extrapolation began had little effect on pulmonary mean transit time and pulmonary blood volume (PBV) calculated by use of the double injection-single sampling method. Similar effects on phi of the level at which extrapolation by a gamma function begins were found with 24 chronic bronchitics. PBV calculated with a gamma function extrapolated from 0.75 X Cmax. downwards and with an exponential function averaged approximately 340 ml and did not differ from one another. The data suggest that the low values of PBV in chronic bronchitis are not an artifact due to the method of extrapolation.

Aged↗

PubMedDate not supplied

Exercise- and allergen-induced asthma do not change the production of Paf-acether by neutrophils and platelets.

Paf-acether, whose role has been suggested in asthma, is a mediator released by stimulated neutrophils, platelets and other cells. Neutrophils and platelets are activated in vivo during exercise or allergen-induced asthma. Upon in vitro stimulation, macrophages from mice treated with an inflammatory stimulus, such as thioglycoccollate, release less paf-acether than macrophages from non-treated mice. We hypothesized that upon in vitro activation platelets and neutrophils should produce less paf-acether after exercise- or allergen-induced asthma. To test this hypothesis, we measured the production of paf-acether by neutrophils and platelets obtained before, 15 and 75 min after exercise in seven normal subjects and five asthmatic subjects with exercise-induced asthma, and in five other asthmatic subjects after specific challenge with Dermatophagoides Pteronyssinus. Purified neutrophils and washed platelets were incubated independently for 10 min at 37 degrees C with no specific activator, with a platelet activator (thrombin, 1 IU.ml-1), a neutrophil activator (opsonized zymosan, 1 mg.ml-1), and both together. We found no significant difference between asthmatic and normal subjects in the amount of paf-acether synthesized by platelets or neutrophils and no fall in the production of paf-acether after exercise- or allergen-induced asthma. However, our method may lack sensitivity in detecting partial activation of these cells and is based on the assumption that changes in peripheral blood cells are representative of changes of these cells in lungs.

Adult↗

PubMedDate not supplied

[Rhinomanometry study of patients with respiratory allergy].

To examine the accuracy of nasal allergic disease, we examined the results of skin tests, measurement of serum specific IgE (RAST), and the nasal response to nasal challenge in 886 patients clinically suspected of having allergic respiratory disease. Nasal responses were assessed by measuring nasal airway resistance by both active anterior and posterior rhinomanometry. Nasal airway resistance was determined 25 min. after intranasal nebulization of saline solution and after administration of increasing doses of allergen (maximum dose = 280 micrograms). The dose of allergen causing a 100% increase over the value obtained after saline (Ri) at a flow rate of 0.15 l.s-1 was taken as the threshold dose (Dl). Our findings were that active anterior and posterior rhinomanometry yield comparable results; in subjects with a positive response to antigen challenge, the increase in nasal airway resistance correlated well with the dose of allergen administered and a significant inverse relationship was found between Ri and Dl; 3) a high level of serum specific IgE accurately predicted nasal responsiveness to a particular allergen, whereas skin tests were often positive to allergens that had no detectable effect on the nasal resistance. We conclude that nasal allergen provocation tests with rhinomanometric measurement of nasal resistance is a useful procedure for diagnosis of nasal allergic disease.

Adolescent↗

PubMedDate not supplied

Refractoriness after hyperventilation-induced asthma.

It is still debated as to whether the bronchospasm induced by hyperpnoea in asthmatic subjects is followed by a period of refractoriness to a subsequent challenge. We studied, therefore, the effect of repeated challenges with eucapnic hyperpnoea in asthmatic subjects and compared it to that in normal subjects. Ten normal and 34 asthmatic subjects were challenged twice with a steady isocapnic hyperventilation (25 l X min-1 X m-2 BSA for 6 min) of dry air at room temperature. The interval between challenges was 30 min in the normal subjects and was 30-60 min in asthmatic subjects to allow for full recovery of FEV1 before the second challenge. In the normal subjects, neither the first nor the second challenge caused a detectable change in FEV1. In the asthmatic subjects, the fall in FEV1 was on average less marked at 5, 8 and 10 min after the second challenge than after the first one (p less than 0.05 by analysis of variance). Analysis of data from individuals showed partial to full refractoriness in 14 of the 34 subjects. In no instance was the fall in FEV1 significantly greater after the second challenge than after the first one. Thirteen other asthmatic subjects were challenged twice at a 30-60 min interval with stepwise increases in ventilation of dry air at room temperature until wheezing or chest tightness occurred or a ventilation of 50 l X min-1 X m-2 BSA was reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗