Takeo Kawashiro

Arterial blood gases in undisturbed resting birds: Measurements in chicken and duck

Arterial blood was sampled in resting, unrestrained and undisturbed birds using a remote-controlled sampling device. With this technique a blood sample of 0.45 ml was obtained for analysis of PO2, PCO2 and pH at the body temperature of the animal. In 5 domestic hens the following mean values were obtained: PA02-82 torr; PACO2=33 torr; pHA=7.52. The average body temperature was TB=41.0 degrees C. In 6 domestic ducks the analysis yielded values of PAO2=82 torr; PACO2=38 torr; pH2=7.49; Tb=41.0 degrees C. Although these values are close to those reported in the literature some discrepancies may be recognized; they can be attributed to respiratory and metabolic changes of blood composition possibly induced by classical sampling procedures.

Distribution of ventilation and of diffusing capacity to perfusion in the lung

We developed a method for estimating the distribution of ventilation (VA) and of diffusing capacity (G) to perfusion (Q) in the lungs. We used O2, CO2 and CO together with six inert gases of widely differing solubility and assumed that mass transfer efficiency of each gas in a gas exchange unit is limited by both VA/Q and G/Q ratios. The underlying lung model comprised 20 units along both the VA/Q and G/Q axes. Using numerical analysis, we transformed the data into a virtually continuous distribution of Q in the VA/Q-G/Q field. We tested the precision of the numerical procedure by examining the recovery of various artificial distributions, and found that distributions with up to two modes could be recovered with reasonable accuracy. Analytical results from 15 patients with interstitial pneumonia of unknown etiology (IPF) revealed the following features. (1) In an early disease stage, most of the lung was operating in the range of normal VA/Q, without a significant contribution of diffusion limitation. (2) An advanced stage of the disease exhibited a widening of VA/Q distribution and either broad unimodal or bimodal distribution of G/Q, extending to G/Q below 10(-3) ml (STPD)/(ml.Torr) with diffusion-limited O2 exchange. (3) Severe diffusion limitation causing disequilibrium of inert gas across the blood-gas barrier was observed in three (far advanced fibrosis; active interstitial inflammation) out of 15 patients. These findings suggest that inhomogeneity of G/Q does exist and may play an appreciable role in causing impairment of gas exchange in patients with interstitial pneumonia.

Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung

BackgroundThe patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.MethodsGuinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue.ResultsThe clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group.ConclusionThese results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

Constriction and dilatation of pulmonary arterial ring by hydrogen peroxide - Importance of prostanoids

Reactive oxygen species (ROS) have been considered as one of the important factors causing acute lung injury associated with alveolar flooding, especially in the case of sepsis, fat embolism, hyperoxic lung damage as well as reperfusion injury (Hefner and Repine, 1989). Among them, hydrogen peroxide (H2O2) and its derivatives are relatively stable as compared to other ROS and are taken notice as the substance altering pulmonary hemodynamics accompanied by alveolar flooding (Archer et al., 1989; Gurtner and Burke-Wolin, 1991; Barnard et al., 1992). Effects of H2O2 on pulmonary circulation is much complicated, namely vasoactive action of H2O2 is dependent on the vascular tone. In other words, H2O2 relaxes the pulmonary vessel when the tone is high but constricts it when the tone is low (Burke-Wolin et al., 1991). Gurtner and Burke-Wolin (1991) reported that vasoconstrictive effect of H2O2 would be mainly mediated through thromboxane A2 (TXA2) generated in the endothelial cells of pulmonary vasculature. However, several authors (Madden et al., 1986; Smith, 1986; Takayasu et al., 1990) showed that arachidonate metabolism might exist not only in endothelial cells but also in smooth muscle cells and fibroblasts in vascular walls, indicating that the conclusion derived by Gurtner and Burke-Wolin (1991) should be reassessed.

Regulation of Blood Flow in Pulmonary Microcirculation by Vasoactive Arachidonic Acid Metabolites – Analysis in Acute Lung Injury

In order to assess the physiological abnormalities and the pathogenesis of adult respiratory distress syndrome (ARDS), especially that associated with pulmonary fat embolism, acute lung injury caused by monounsaturated nonsterified fat oleic acid (cis-9-octadecenoic acid) has been widely used in animal experiments. This lung injury results in an extensive, multifocal, and heterogeneously distributed lung damage with alveolar flooding, interstitial edema and microatelectasis. The ability to reduce the perfusion entering into damaged and edematous areas is essentially important in preserving blood oxygenation in ARDS.

Ventilation-perfusion inequality and diffusion impairment in acutely injured lungs

To assess the significant role of diffusion impairment and its unequal distribution in acutely injured lungs with alveolar flooding, oleic acid was intravenously injected into twenty-five mongrel dogs. The animals were divided into two groups, A and B. 0.1% CO in air was delivered, as an inspired gas, to the animals of group A. Simultaneously, saline containing a trace amount of six foreign inert gases was infused through a peripheral vein. While allowing the animals in group B to breathe air, saline containing ethylene, acetylene and freon 22 was infused. After injection of oleic acid, group A revealed increase in intrapulmonary shunt accompanied by a marked broadening of ventilation-perfusion (VA/Q) and diffusing capacity-perfusion (G/Q) distributions. A considerable amount of total cardiac output was received by the lung areas with low G/Q ratios where significant diffusion limitation was predicted to occur. Group B showed that excretion of freon 22 (gas with lower diffusivity) in injured lungs was considerably distorted as compared to those of ethylene and acetylene (gases with higher diffusivities), again ascertaining the importance of diffusion limitation in lungs with exudate in alveolar regions.

Estimation of the distribution profile of airway resistance in the lungs

The distribution profile of resistance in a series lung model consisting of airways of 23 generations with alveoli was estimated in 10 healthy subjects and 7 subjects with chronic pulmonary emphysema. Forced oscillation was applied to the subjects at the mouth using a complex wave composed of sine waves at frequencies through the range 4 to 20 Hz in 1-Hz steps. The pleural pressure was measured with a catheter-tip micromanometer, which was installed in an esophageal balloon. The frequency dependency of the pulmonary impedance was analyzed using a penalty function method, and a stable estimate of the distribution profile of resistance in the lungs was thus obtained. The central airway resistance (defined as the resistance from generation 0 to generation 7) was estimated as 1.18 +/- 0.37 cm H2O/liter/sec in the healthy subjects and 1.03 +/- 1.13 cm H2O/liter/sec in the subjects with chronic pulmonary emphysema. The peripheral airway resistance (defined as the resistance from generation 8 to generation 23) was estimated as 0.06 +/- 0.03 cm H2O/liter/sec in the healthy subjects and 6.38 +/- 3.77 cm H2O/liter/sec in the subjects with chronic pulmonary emphysema.

Cell‐associated IL‐8 in human blood monocytes: Analysis by flow cytometry

Several cell-associated cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor, exist on the cell surface and are biologically active. Although extracellular IL-8, a potent chemotactic factor for primarily neutrophils, has been studied extensively, cell-associated IL-8 has barely been studied. In this study, we analyzed the intracellular and cell-surface IL-8 in human blood monocytes in vitro by using flow cytometry and predicted the biological activity of the cell-associated IL-8 in vivo. After fixation with paraformaldehyde, mononuclear cells were divided into two subgroups. One subgroup was left untreated to study cell-associated antigens, and the other subgroup was permeabilized with saponin to detect intracellular antigens. In lipopolysaccharide (LPS)-stimulated monocytes, IL-8 was detected solely intracellularly, whereas both the intracellular and cell-surface IL-1 beta was detectable. In a time-course study, the intracellular IL-8 increased in response to LPS stimulation, but the cell-surface IL-8 was undetectable throughout the course. In an LPS-stimulated monocytic cell line, both ELISA and flow cytometry detected the quantitative change of the intracellular IL-8. The dissimilar localization between IL-8 and IL-1 beta within cells was confirmed by the immunohistochemical analysis. In summary, LPS stimulation induced a time-dependent increase in intracellular but not cell-surface IL-8 in monocytes. Thus, it is unlikely that the cell-associated IL-8 is functioning physiologically. The semiquantitative flow cytometric procedure may be useful for simultaneous examination for cell-surface and intracellular cytokines.

Effects of 5-Hydroxytryptamine Inhibition on Gas Exchange and Pulmonary Hemodynamics in Acute Canine Pulmonary Embolism

5-Hydroxytryptamine (Serotonin; 5-HT), a potent vasoconstrictor of pulmonary arteries, has been reported to play an important role in cardiopulmonary dysfunction that accompanies pulmonary embolization (Huval et al.,1983). The quantitative effects of 5-HT on gas exchange efficiency, however, have not been systematically investigated in pulmonary embolism. Using a new type of selective serotonin receptor antagonist, we examined the distribution of ventilation-perfusion (VA/Q) ratios and pulmonary hemodynamics to clarify the effects of serotonin on gas exchange in acute canine pulmonary embolism.

Roles of antioxidant enzymes in erythrocytes on hypoxic pulmonary vasoconstriction

Hypoxie pulmonary vasoconstriction (HPV) is of importance in egulating the distribution of blood flow in the lung, thus allowing the lung to maintain a pertinent matching between ventilation and blood flow. Recently, several authors (cf. Archer et al, 1989b) have reported that endogenous products of reactive O2 species (ROS) in the lung are the important factor for initiating HPV.