Airway responses to inhaled ouabain in subjects with and without asthma.

Challenges with ouabain and histamine were performed a week apart in 10 patients with asthma and 5 normal subjects. Concentrations were increased cumulatively until specific airway conductance decreased by 30% or the maximal concentration of 1.0% was reached. At low concentrations, ouabain induced bronchodilatation in six patients who had asthma. Bronchodilatation gradually decreased with increasing concentrations and was followed by bronchoconstriction in two patients with asthma who had high airway sensitivity to histamine. Ouabain caused only bronchoconstriction in three patients with severe asthma. The normal subjects showed mild bronchodilatation or no response to ouabain. Several possible biochemical mechanisms may be responsible for the bronchodilatory response to low doses of ouabain, such as stimulation of adenylate cyclase or (Na+,K+)-adenosine triphosphatase. The absence of a bronchodilatory response to ouabain in patients with severe asthma suggests an impairment in the activity of these enzymes.

Effects of chest wall on volume and strain patterns in canine lungs.

Lobar functional residual capacity-to-total lung capacity ratios (FRC/TLC) and strains in five supine anesthetized dogs were determined from volumes and side lengths of tetrahedra formed by multiple intraparenchymal markers whose positions were determined roentgenographically. Strain is related to fractional changes in length of elements in a Cartesian coordinate system and was used to describe parenchymal distortion. Volumes and strain patterns were compared in three states: intact dogs, after transection of forelimb structures to relieve traction on the chest wall, and in dogs' excised lungs. Removing traction (NT) decreased the plethysmographically determined FRC and the upper-to-lower lobe ratio (UL/LL) for FRC/TLC. The ratio in the NT state was more like the ratio in the excised lungs (UL/LL approximately equal to 1) than in the intact dog (UL/LL greater than 1). Strain patterns were similar between the intact and the NT states, indicating no lobar shape change at FRC between these two states. Strain in the excised lungs differed greatly from strains in the intact and NT states. We conclude that forelimb traction alters volume distribution between lobes and that lung-chest wall interactions are important in determining volume and strain patterns.

Effects of acute pleural effusion on respiratory system mechanics in dogs.

We determined regional (Vr) and overall lung volumes in six head-up anesthetized dogs before and after the stepwise introduction of saline into the right pleural space. Functional residual capacity (FRC), as determined by He dilution, and total lung capacity (TLC) decreased by one-third and chest wall volume increased by two-thirds the saline volume added. Pressure-volume curves showed an apparent increase in lung elastic recoil and a decrease in chest wall elastic recoil with added saline, but the validity of esophageal pressure measurements in these head-up dogs is questionable. Vr was determined from the positions of intraparenchymal markers. Lower lobe TLC and FRC decreased with added saline. The decrease in upper lobe volume was less than that of lower lobe volume at FRC and was minimal at TLC. Saline increased the normal Vr gradient at FRC and created a gradient at TLC. During deflation from TLC to FRC before saline was added, the decrease in lung volume was accompanied by a shape change of the lung, with greatest distortion in the transverse (ribs to mediastinum) direction. After saline additions, deflation was associated with deformation of the lung in the cephalocaudal and transverse directions. The deformation with saline may be a result of upward displacement of the lungs into a smaller cross-sectional area of the thoracic cavity.

Pulmonary diagnostic procedures in the critically ill.

When faced with a critically ill patient with new pulmonary infiltrates on chest roentgenograms, the physician must choose the appropriate diagnostic procedure on the basis of the expected yields versus the potential complications. The first steps in any patient should include discontinuation of any nonessential medications, careful evaluation of fluid status to exclude cardiogenic pulmonary edema, and a review of likely diagnoses based on the patient's underlying disease. Although not likely to be of immediate utility, obtaining cultures of blood and other body fluids or sites and serologic testing may provide helpful information when combined with other procedures. Bronchoscopy is a reasonable first step in patients with a slow progression of disease or in those in whom the pulmonary process is discovered early in its course. As these patients often present with several of the known risk factors for complications with bronchoscopy, the decision to perform this procedure should not be made lightly. Transbronchoscopic lung biopsy adds additional risk to bronchoscopy but also increases the diagnostic yield considerably over lavages, brushing, and bronchial washings. Open lung biopsy offers high diagnostic yields and relatively low rates of serious complications. Because of the invasive nature of the procedure, there is often reluctance to perform it. In patients with rapidly progressive disease or conditions that make the risk of bronchoscopy unacceptably high, such as severe hypoxemia, bleeding diathesis, or cardiac compromise, prompt diagnosis requires that the physician consider open lung biopsy as a first diagnostic procedure. The physician must also consider whether making a specific diagnosis will be of benefit to the patient. Potential benefits of a specific diagnosis include stopping unnecessary empirical (and potentially toxic) therapies, instituting correct and specific therapy, and thus decreasing morbidity and mortality. The impact of specific diagnosis on morbidity and survival is often difficult to demonstrate. Discouraging notes have been sounded by studies of the effect of bronchoscopic or surgical diagnosis on the ultimate outcome for patients. For bronchoscopy with transbronchoscopic lung biopsy, although the overall diagnostic rate was 60 per cent, no difference in survival was noted between patients in whom a diagnosis was made and those in whom the nature of the pulmonary process remained unknown. Similarly, in a series of patients who underwent open lung biopsy, although the results of biopsy led to a therapeutic change in 70 per cent of the patients, only 16.5 per cent of the patients benefited from this change.(ABSTRACT TRUNCATED AT 400 WORDS)

Reduced thermoregulatory null zone in postmenopausal women with hot flashes.

OBJECTIVE: Most menopausal hot flashes are preceded by small elevations in core body temperature. If the thermoneutral zone between the thresholds for sweating and shivering is reduced in women with symptoms, the triggering mechanism for hot flashes could be explained. STUDY DESIGN: We studied 12 postmenopausal women with symptoms and 8 without symptoms. We measured body temperatures with a rectal probe, an ingested telemetry pill, and a weighted average of rectal and skin temperatures. Each woman underwent 3 experimental sessions: determination of the sweating threshold by body heating, determination of the shivering threshold by body cooling, and replication of the sweating threshold with exercise. RESULTS: The women with symptoms had significantly smaller interthreshold zones than did the symptom-free women for all 3 measures of body temperature: rectal temperature, 0.0 degrees C +/- 0.06 degrees C versus 0.4 degrees C +/- 0.18 degrees C (P <.005); telemetry pill temperature, 0.0 degrees C +/- 0.11 degrees C versus 0.4 degrees C +/- 0.18 degrees C (P <.005); and mean body temperature, 0.8 degrees C +/- 0.09 degrees C versus 1.5 degrees C +/- 0.20 degrees C (P <. 0006). Sweat rates were significantly higher among the women with symptoms (0.06 +/- 0.002 mg. cm(-2). min(-1)) than among the women without symptoms (0.03 +/- 0.001 mg. cm(-2). min(-1), P <.05). Sweating thresholds during exercise did not significantly differ from those during body heating. During exercise all the women with symptoms and none of the women without symptoms had hot flashes. CONCLUSIONS: Menopausal hot flashes in women with symptoms may be triggered by small elevations in body temperature acting within a reduced thermoneutral zone.

Quiet-breathing vs. panting methods for determination of specific airway conductance.

Specific airway conductance (sGaw) was measured during quiet breathing and during panting in 21 normal subjects and 10 patients with obstructive lung disease. The direct method used does not require measuring thoracic gas volume (TGV). Coefficients of variation were 5.5% for panting and 5.1% for quiet breathing. Interobserver variability was 4.7% in the quiet-breathing method and 6.3% in the panting method. The two methods gave equivalent results for sGaw. A slightly greater sGaw was found by the panting method in normal subjects with the highest sGaw values, probably due to widening of the oropharynx-glottis during panting. In six normal subjects studied for intrasubject variability over time, no significant diurnal or day-to-day variability was seen by either method. We conclude that the quiet-breathing method is a simple valid means of determining sGaw and utilizes a physiological respiratory maneuver. Obviation of the need to measure TGV is advantageous. Results are equivalent to those of the panting method and variability is similar.

Studies on circulating soluble fibrin: separation of 125I-Des-AB fibrin and 131I-fibrinogen by gel filtration.

The behaviour of labelled des-AB fibrin in plasma was studied by gel filtration after it had been injected into rabbits. Purified rabbit [125I]des-AB fibrin was prepared by clotting of [125I]fibrinogen by thrombin and solubilizing the formed clot in buffered 3 M urea. Gel filtration of this material on urea-equilibrated columns showed a single peak identical to the elution profile of fibrinogen. This indicated the existence of monomeric des-AB fibrin. When plasma from rabbits injected with monomeric [125I]des-AB fibrin and [131I]fibrinogen was gel-filtered through plasma-equibrated columns, two separate peaks of radioactivities were obtained. The first peak eluted mainly with the void volume and contained [125I]des-AB fibrin whereas the second peak eluting within the fractionation range contained [131I]fibrinogen. Identical elution profiles were obtained in in vitro studies when monomeric [125I]des-AB fibrin was mixed with plasma containing [131I]fibrinogen and gel-filtered through plasma-equilibrated columns. We conclude from these studies that monomeric des-AB fibrin formed high-molecular weight aggregates or changed its conformation posing as a larger molecule than fibrinogen when injected into rabbits. No complex formation between des-AB fibrin and fibrinogen was observed as [131I]fibrinogen was not incorporated into des-AB fibrin aggregates. Thus, soluble des-AB fibrin can circulate in the blood without forming fibrin-fibrinogen complexes.

[Arrhythmogenic right ventricular dysplasia as a cause of "sudden cardiac death" with survival]. / Arrhythmogene rechtsventrikuläre Dysplasie als Ursache eines überlebten plötzlichen Herztodes.

HISTORY: A 42 year old woman was resuscitated from ventricular fibrillation. 5 months previously she had a syncope. Her nephew had died of sudden cardiac death at the age of 25 years. INVESTIGATIONS: There was no evidence for ST segment elevation, myocardial infarction or pulmonary embolism. The ECG showed right precordial T wave inversion. Coronary artery disease was excluded angiographically. Echocardiography and angiography revealed inferior wall akinesia of the right ventricle with normal left ventricular function and chamber size. Ventricular fibrillation could not be reproduced by programmed stimulation of the right ventricle during an electrophysiologic study. Results of endomyocardial biopsy of the right ventricle showed a focal fibrous infiltration of the myocardium. Magnetic resonance imaging confirmed inferior wall abnormalities of the right ventricle without typical fatty infiltration in the right ventricular myocardium. CLINICAL COURSE: The patient recovered rapidly without neurologic deficits. Arrhythmogenic right ventricular dysplasia was suspected, and a cardioverter defibrillator (ICD) was implanted. Within 6 months after implantation the ICD memory showed no evidence of ventricular fibrillation. CONCLUSION: Arrhythmogenic right ventricular dysplasia is an important cause of ventricular fibrillation with a potential risk of sudden cardiac death in young persons. Concealed arrhythmogenesis as an early manifestation of right ventricular dysplasia is difficult to detect.

Pulmonary function in relapsing polychondritis.

The pulmonary mechanics and bronchoscopic findings in 5 patients with relapsing polychondritis were studied to evaluate the mechanism of obstruction. Two of the patients did not have clinical symptoms referable to the respiratory tract: pulmonary function was normal in 1 patient and was suggestive of mild restriction in the other. Three patients had dyspnea; pulmonary function studies revealed expiratory and inspiratory obstruction in all 3. The maximal flow-static recoil curves demonstrated that the expiratory obstruction was due predominantly to airway abnormality and not to loss of elastic recoil forces of the lung. The bronchoscopic appearance of the extrathoracic airway during quiet breathing did not accurately reflect pulmonary function results. One patient had a visually normal upper airway but greatly reduced maximal inspiratory flow rates, whereas another patient had pronounced narrowing of the upper airway but only a modest reduction of maximal inspiratory flow rates. The bronchoscopic appearance of the intrathoracic airway during quiet breathing did relate well to maximal expiratory flow rates. We conclude that in our group of patients the predominant mechanism of expiratory obstruction in relapsing polychondritis is due to airway abnormality. Although the bronchoscopic and radiographic findings are useful, spirometry is more important in determining functional abnormality.