Daniel H. Simmons

Relation Between Lung Volume and Pulmonary Vascular Resistance

Ten experiments were conducted on anesthetized dogs ventilated with a Starling pump and breathing oxygen. While tidal volume, respiratory rate, and arterial pH and pCO2 were kept constant, lung volume was varied by using either a negative, zero, or positive end-expiratory pressure, leading to average changes in lung volume of −32, 0, and +75 per cent. Pulmonary vascular resistance (PVR) increased with either decreased or increased lung volume, indicating that the relationship between resistance and lung volume is a U-shaped curve. Since the transmural distending pressures of large pulmonary vessels either increased or remained unchanged during these procedures, changes in PVR cannot be ascribed to changes in systemic circulatory dynamics, such as cardiac output. It was noted that cardiac output increased with negative end-expiratory pressure (effectively, negative-pressure breathing) and decreased with positive end-expiratory pressures (effective, positive-pressure breathing), as previously reported. A hypothesis is presented for explaining the U-shaped curve relating resistance and lung volume.

The significance of regional pulmonary function changes in bronchial asthma

Abstract Regional ventilation and perfusion relationships were investigated with radioxenon and macroaggregated radioalbumin in thirty-four asthmatic subjects. The results, as well as those of spirometry and blood gas studies, were correlated with the patients symptoms. It was found that all measurements became increasingly abnormal as symptoms increased but were readily reversible with treatment. Areas of hypoventilation generally showed decreased perfusion but perfusion was frequently less affected than ventilation. This ventilation-perfusion imbalance appears to be widespread in asthma and explains the common observation of hypoxemia despite over-all hyperventilation.

Diagnostic value of fiberoptic bronchoscopy in metastatic pulmonary tumors.

The fiberoptic bronchoscopic procedure (with brushings, washings, and biopsies) was performed and specimens of sputum were obtained before the procedure in 37 patients with cancer metastatic to the lung. Of the 37 patients studied, endobronchial lesions were visualized at bronchoscopic examination in 14 (group 1), and no endobronchial lesion was seen in 23 (group 2). The yield of bronchial brushing and washings was not significantly different in group 1 and 2, whereas examination of sputum obtained before the bronchoscopic procedure and bronchial biopsy in group 1 yielded higher results than the same procedures in group 2. The radiographic findings did not influence the yield with any of the bronchoscopic procedures. The overall positive diagnostic yield from fiberoptic bronchoscopic procedures among these patients was 54 percent (20/37), regardless of their bronchoscopic or radiologic findings.

Nitrogen Dioxide and the Erythrocyte Redox State

Normal human erythrocytes were exposed for two hours at 38 C to an atmosphere of air containing variable concentrations of nitrogen dioxide, in order to detect any primary cytoplasmic effect of NO2 on the calculated oxidation-reduction (redox) ratio ([NAD+]/[NADH]) of a mitochondria-free cell. Substantial increases in the redox ratio were noted only when NO2 concentrations exceeded 15 ppm. In the range of 15 to 500 ppm NO2, the increase in the redox ratio significantly correlated with the NO2 concentration (r=.71; p less than .01). Intracellular to extracellular anion distribution ratios for chloride, lactate, and pyruvate were similar in NO2 and non-NO2 exposed cells, suggesting absence of a substantial hemolytic effect. These data identify a direct cytoplasmic NO2-induced biochemical change that may be mediated by a mechanism other than lipid peroxidation. Alteration of hemoglobin or NAD-NADH-dependent enzyme activity is suggested.

Organ and whole body cell pH.

Summary Intracellular pH values of 11 organs of the rat were compared with whole body cell pH calculated from the distribution of tritiated water, 14C-DMO, and 36Cl. Heart and skeletal muscle cell pH were similar to whole body cell pH; testes, lung, kidney, intestines, skin, liver, and skeleton were higher while brain and spleen were lower. When sulfate rather than chloride spaces were used as an estimate of extracellular fluid volume, skeletal muscle pH was little changed but spleen and kidney were higher and skin and liver were lower. The close approximation of skeletal muscle and whole body cell pH is due to the large fraction of isotopes present in muscle and the lack of significant or large disproportionate collection of isotopes elsewhere.

Determination of Total Cation-Forming Mineral Elements in Feces And Urine and Its Relation to Renal “Net Acid” Excretion.

Summary A relatively simple titrimetric method for determining total cation-forming mineral elements in urine and feces is described and demonstrated to yield dependable values. Addition of fecal minerals to an otherwise constant diet in rats is shown to effect an increased urinary excretion of total cation-forming mineral elements together with a correspondingly decreased renal “net acid” excretion. The theoretical basis for this result and for analogous results of others is discussed. It is concluded that the extent to which cation-forming mineral elements are excreted in the feces rather than in urine can considerably influence the extent of renal “net acid” excretion. Addendum: While the preceding report was in press, studies by Lennon, Lemann and Litzow(13,14) appeared, in which collective values for Na+, K+, Ca++ and Mg++ (ions derivable from cation-forming elements) in diet and feces, respectively, are calculated as a negative and positive component, respectively, of “total effective acid production” (”TEAP”) in the organism, a value which is shown normally to be balanced by renal “net acid” excretion (13). The value for fecal excretion of the cation-forming mineral elements therefore appears as a positive component of the “TEAP” value, and since the latter is normally balanced by the renal “net acid” value, it appears that the described calculation of “TEAP”(13) takes into account the influence of fecal excretion of cation-forming mineral elements on renal “net acid” excretion. However, the nature of the calculation suggests that the authors (13) are unaware of the relationships shown in Equation 2, which account for this influence. The complete operational definition proposed (13) for “TEAP” may be expressed by the following equation, in which “absorbed” designates values obtained by subtracting fecal from dietary values:

Effect of assisted mechanical ventilation on arterial carbon dioxide tension of normal anesthetized dogs.

AbstractThe effect of assisted mechanical ventilation (application of positive airway pressure during inspiration triggered by minimal inspiratory effort) on breathing pattern and PaCO2 of five normal anesthetized dogs was studied. Ventilation (and presumably respiratory drive) was reduced by barbiturate anesthesia sufficient to raise mean PaCO2 during spontaneous breathing approximately 8 torr. Respiratory muscle work was “unloaded” by assisted ventilation using pressure- and volume-limited ventilators. Thirty-minute periods of spontaneous breathing were alternated with 30-min periods of assisted ventilation.Responses to both pressure- and volume-limited ventilators were similar. PaCO2 decreased in proportion to the peak pressure applied, approximately 4 torr (statistically significant) at the maximum peak pressure (21.2±0.4 cm H2O), although increases in

Effect of assisted ventilation on respiratory drive of normal anethetized dogs

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