Measurement of pulmonary tissue volume and blood flow in persons with normal and edematous lungs.

We measured pulmonary tissue volume (Vt) and pulmonary capillary blood flow (Qc) by a rebreathing method using two soluble gases, acetylene (C2H2) and dimethyl ether (DME), in 32 normal subjects and 14 patients who had had pulmonary edema. In 18 of the normal subjects, studies were performed at three or more different rebreathing volumes (VA). To normalize for differences in body size, results were expressed as the ratio of Vt or VA to predicted total lung capacity (TLC). We found that 1) changes in VA/TLC had a significant effect on Vt/TLC and Qc measured with both gases, 2) the range of normal values for Vt was best defined by expressing the relationship between Vt/TLC and VA/TLC, 3) using this approach, many patients with clinically mild or inapparent pulmonary edema had abnormal values of Vt, and 4) when comparing mean values of C2H2 and DME in 82 simultaneous measurements at constant VA/TLC, Vt was significantly higher in 87% (71/82) and Qc in 63% (52/82) of the paired tests.

Influence of hematocrit and temperature on solubility of acetylene and dimethyl ether.

Estimation of pulmonary capillary blood flow (Qc) and tissue volume (Vt) by rebreathing acetylene (Ac) and dimethyl ether (DME) is dependent on the blood-gas partition coefficient (lambda) of these gases. We investigated the effects of hematocrit (Hct) and temperature on lambda. Human and canine blood was equilibrated at different Hct for 40 min at 37.5 degrees C with 1% Ac and 1% DME in air. Gas concentration in the headspace was measured by gas chromatography. lambda Ac increased with increasing Hct, suggesting a slight lipid affinity, whereas lambda DME decreased with increasing Hct, displaying the known blood-water content dependence. The influence of temperature on lambda in the range of 32--47 degrees C was investigated also. lambda Ac and lambda DME decreased as the temperature was raised, in accordance with the Gibbs-Helm-holtz equation. Empirical equations were derived to relate lambda to to Hct and temperature.

Alteration of pulmonary function in intravenous drug abusers. Prevalence, severity, and characterization of gas exchange abnormalities.

We examined the influence of chronic intravenous drug abuse on respiratory function in 512 consecutive drug addicts by obtaining respiratory histories, pulmonary function tests and chest roentgenograms. Two hundred and fourteen (42 per cent) had carbon monoxide-diffusing capacities (DLCO) of less than 75 per cent predicted (mean 65.7 per cent), and in 38 per cent reduced DLCO was the sole pulmonary function test abnormality. Obstructive lung disease attributed to asthma or chronic bronchitis was observed in 6 per cent and a restrictive defect due to interstitial lung disease was observed in 7 per cent. Exercise limitation due to dyspnea among those patients with altered pulmonary function was uncommon except in those with obstructive or restrictive lung disease. Roentgenographic evidence of pulmonary hypertension was not observed in any of the patients. Gas exchange measured at rest and during exercise in 11 patients with a low DLCO and in three patients with restrictive lung disease and a low DLCO revealed an increased alveolar-arterial oxygen difference but normal minute ventilation, dead space-to-tidal volume ratio and absence of abnormal right-to-left shunts. We conclude that alterations in pulmonary function in drug addicts due to foreign particle emboli are very common but that significant respiratory symptoms are unusual and that abnormalities in gas exchange during exercise are mild.

Noncardiac pulmonary edema.

Several mechanisms leading to noncardiac pulmonary edema have been reviewed. Common features are damage to and increased permeability of vascular endothelium, interstitial and alveolar edema fluid high in protein content, increased pulmonary vascular resistance and pressure, nondependent distribution of the edema and normal left atrial or wedge pressure. The available evidence suggests that in some instances the sites of leakage are the pulmonary arterial walls and, perhaps in some, overperfused, damaged capillary beds. Therapeutic obestives differ from those in cardiac pulmonary edema in that efforts are directed toward a reduction in pulmonary blood flow and pulmonary arterial pressure during the period that endothelial healing is taking place.

Abnormal membrane protein of red blood cells in hereditary spherocytosis.

We present evidence that the hereditable hemolytic disease, hereditary spherocytosis (HS), involves an abnormality in protein of the red cell membrane. Unlike that from normal red cells, lipid-free proteins extracted from HS red cell membranes fail to increase in sedimentation rate when treated with cations; such treatment of normal membrane proteins has been shown by others to cause the formation of microfilaments. That microfilament formation might be defective in HS red cell membranes is supported by observations with vinblastine. This compound, a potent precipitant of filamentous, structure proteins throughout phylogeny, precipitates significantly less HS membrane protein than normal. The resistance of HS membrane protein to changes in conformation by cations is observable at the cellular level as well. That is, both normal and HS red cells agglutinate after repeated washing and suspension in electrolyte-free media. Tiny concentrations of Ca(++) (5 x 10(-5) M) changes the surfaces of normal cells in such a way as to cause disagglutination; HS red cells resist this change and remain agglutinated unless Ca(++) concentrations are increased many-fold. We conclude that membrane ("structure") proteins of HS red cells are genetically altered in such a way as to interfere with their proper conformation, perhaps into fibrils. Potentially many mutations in membrane proteins might preclude this alignment, with the result that normal erythrocyte biconcavity and plasticity is prevented and the clinical syndrome of hereditary spherocytosis is manifest.