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Biomedical subjects

M Peters-Golden

Publications and source records attributed to M Peters-Golden.

At least 91 records · Page 5Linked to original sources
PubMed1989

Multiple defects in arachidonate metabolism in alveolar macrophages from young asymptomatic smokers.

This study was undertaken to localize and determine the relative importance of potential biochemical defects in the release and metabolism of arachidonic acid (AA) in alveolar macrophages (AMs) from asymptomatic smokers. Using high-performance liquid chromatography and radioimmunoassay, we compared the metabolism of both endogenously released and exogenously supplied AA in AMs and autologous peripheral blood monocytes (PBMs) from nine healthy nonsmokers and eight healthy smokers. AMs from both groups incorporated similar amounts of radiolabeled AA into cellular lipids. However, AMs from smokers released only about half as much radioactivity as free AA and its metabolites in response to ionophore A23187, when compared to cells from nonsmokers; this suggests that net phospholipase activity was decreased in smokers. In addition, AMs from smokers synthesized less of total cyclooxygenase and 5-lipoxygenase products than did cells from nonsmokers, both constitutively and in response to A23187 as well as the particulate agonist zymosan. Furthermore the metabolism of exogenous AA to both cyclooxygenase and 5-lipoxygenase products was reduced in smoker cells compared to nonsmoker cells. Inverse relationships between eicosanoid synthesis and intensity of smoking were observed. No differences between smoker and nonsmoker PBMs were found. These results show that the major defect in smoker AMs is at the phospholipase level, with additional defects being present at the levels of the cyclooxygenase and 5-lipoxygenase pathways. All these abnormalities are compartmentalized to the mononuclear phagocyte population of the lung.

Adenosine Triphosphate↗
PubMed1988

Hydrogen peroxide inhibits alveolar macrophage 5-lipoxygenase metabolism in association with depletion of ATP.

We have previously shown that the biologically important reactive oxygen metabolite hydrogen peroxide (H2O2) stimulates arachidonic acid (AA) release and thromboxane A2 synthesis in the rat alveolar macrophage. We have now investigated the effects of H2O2 on alveolar macrophage 5-lipoxygenase metabolism. H2O2 failed to stimulate detectable synthesis of leukotriene B4, leukotriene C4, or 5-hydroxyeicosatetraenoic acid (5-HETE) as determined by reverse-phase high performance liquid chromatography (RP-HPLC) and sensitive radioimmunoassays (RIAs). This was not explained by oxidative degradation of leukotrienes by H2O2 at the concentrations used. Moreover, RIA and RP-HPLC analyses demonstrated that H2O2 dose-dependently inhibited synthesis of leukotriene B4, leukotriene C4, and 5-HETE induced by the agonists A23187 (10 microM) and zymosan (100 micrograms/ml), over the same concentration range at which it augmented synthesis of the cyclooxygenase products thromboxane A2 and 12-hydroxy-5,8,10-heptadecatrienoic acid. Four lines of evidence suggested that H2O2 inhibited alveolar macrophage leukotriene and 5-HETE synthesis by depleting cellular ATP, a cofactor for 5-lipoxygenase. 1) H2O2 depleted ATP in A23187- and zymosan-stimulated alveolar macrophages with a dose dependence very similar to that for inhibition of agonist-induced leukotriene synthesis. 2) The time courses of ATP depletion and inhibition of leukotriene B4 synthesis by H2O2 were compatible with a rate-limiting effect of ATP on leukotriene synthesis in H2O2-exposed cultures. 3) Treatment of alveolar macrophages with the electron transport inhibitor antimycin A prior to A23187 stimulation depleted ATP and inhibited leukotriene B4 and C4 synthesis to equivalent degrees, while thromboxane A2 production was spared. 4) Incubation with the ATP precursors inosine plus phosphate attenuated both ATP depletion and inhibition of leukotriene B4 and C4 synthesis in alveolar macrophages stimulated with A23187 in the presence of H2O2. Our results show that H2O2 has the capacity to act both as an agonist for macrophage AA metabolism, and as a selective inhibitor of the 5-lipoxygenase pathway, probably as a result of its ability to deplete ATP. Depletion of cellular energy stores by oxidants generated during inflammation in vivo may be a means by which the inflammatory response is self-limited.

Adenosine Triphosphate↗
PubMed1988

Inhibitory effect of exogenous arachidonic acid on alveolar macrophage 5-lipoxygenase metabolism. Role of ATP depletion.

Although a variety of agonists have the capacity to stimulate the release of endogenous arachidonic acid (AA) from macrophage lipids and its subsequent metabolism to both cyclooxygenase and 5-lipoxygenase eicosanoids, including leukotrienes (LT), previous work suggests that exogenously supplied arachidonate is metabolized preferentially to cyclooxygenase products and mono-hydroxyeicosatetranenoic acids rather than LT. We have compared the metabolism of endogenous and exogenous AA in cultured rat alveolar macrophages and have further examined the effect of exogenous fatty acids on eicosanoid synthesis stimulated by the calcium ionophore A23187 and the particulate agonist zymosan. As reported by others, exogenous AA was metabolized to large amounts of cyclooxygenase products, 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid, but far lesser amounts of all 5-lipoxygenase products. However, whereas exogenous AA augmented the synthesis of cyclooxygenase metabolites in both A23187- and zymosan-stimulated cells, it dose-dependently inhibited the synthesis of LT. Inasmuch as unsaturated fatty acids, including AA, uncouple oxidative phosphorylation, and because 5-lipoxygenase activity depends on ATP, we examined the possibility that ATP depletion was responsible for the inhibition of LT synthesis by exogenous AA. Arachidonate depleted cellular ATP in a dose-dependent fashion similar to its inhibition of LT synthesis. In addition, the other unsaturated fatty acids, linolenic and eicosatrienoic, but not the saturated fatty acids, palmitic or stearic, both depleted ATP and inhibited A23187-induced LT synthesis. These data suggest that the relative lack of synthesis of LT from exogenous AA is related to the ability of this unsaturated fatty acid to function as an inhibitor, as well as a substrate, of 5-lipoxygenase. Our results further suggest that this inhibition of 5-lipoxygenase may be mediated by ATP depletion.

Adenosine Triphosphate↗
PubMed1988

Hypophosphatemia-associated respiratory muscle weakness in a general inpatient population.

Although hypophosphatemia has been implicated as a cause of respiratory failure, its impact on respiratory muscle function in patients hospitalized for other reasons remains to be determined. Maximal inspiratory pressures (MIP) and maximal expiratory pressures (MEP) were measured at the bedside in 23 hospitalized patients with serum phosphate levels less than 2.5 mg/dl, and these measurements were repeated daily during phosphate repletion until serum phosphate levels reached the normal range. A control group consisted of 11 normophosphatemic inpatients. Sixteen of 23 hypophosphatemic patients, but none of the control patients (p less than 0.001), exhibited respiratory muscle weakness, defined as a MIP less than 40 cm H2O or a MEP less than 70 cm H2O. The mean initial MIP and MEP values were also significantly lower for the hypophosphatemic group. A significant correlation existed between initial phosphate level and initial MIP value (r = 0.50, p less than 0.02). With phosphate repletion, mean +/- SD MIP increased from -37 +/- 26 cm H2O to -49 +/- 24 cm H2O (p less than 0.003) and MEP from 60 +/- 20 cm H2O to 69 +/- 19 cm H2O (p less than 0.02). It is concluded that respiratory muscle weakness is common among hypophosphatemic patients and improves with phosphate repletion.

Aged↗
PubMed1988

The oral gold compound auranofin triggers arachidonate release and cyclooxygenase metabolism in the alveolar macrophage.

We examined the effect of in vitro incubation with the oral gold compound auranofin (AF) on arachidonic acid (AA) release and metabolism by rat alveolar macrophages (AMs). AF stimulated dose- and time-dependent release of 14C-AA from prelabeled AMs, which reached 4.7 +/- 0.3% (mean +/- SEM) of incorporated radioactivity at 10 micrograms/ml for 90 min, as compared to 0.5 +/- 0.1% release following control incubation for 90 min (p less than 0.001). Similar dose- and time-dependent synthesis of thromboxane (Tx) A2 (measured as TxB2) and prostaglandin (PG) E2 was demonstrated by radioimmunoassay of medium from unlabeled cultures, reaching 18-fold and 9-fold, respectively, of the control values at 10 micrograms/ml AF for 90 min (p less than 0.001 for both). AF-induced TxB2 and PGE2 synthesis was inhibited by indomethacin as well as by pretreatment with methylprednisolone. No increase in the synthesis of immunoreactive leukotrienes (LT) B4 or C4 was noted at any dose or time of AF. High performance liquid chromatographic separation of 14C-eicosanoids synthesized by prelabeled AMs confirmed that AF induced the release of free AA and its metabolism to cyclooxygenase, but not 5-lipoxygenase, metabolites. The ability of AF to trigger macrophage AA metabolism may be relevant to the exacerbation of certain inflammatory processes which sometimes accompany gold therapy.

Animals↗
PubMed1988

Hydrogen-peroxide-induced arachidonic acid metabolism in the rat alveolar macrophage.

Mounting evidence suggests that reactive oxygen metabolites can initiate the release and metabolism of arachidonic acid (AA). We therefore examined the effects of hydrogen peroxide (H2O2), a biologically relevant oxygen metabolite, on AA release and cyclooxygenase metabolism by the rat alveolar macrophage (AM). At concentrations between 10(-4) and 10(-3) M, which were largely noncytotoxic as assessed by chromium release, H2O2 exposure for 30 min caused a steep dose-dependent increase in AA release that peaked at approximately 5-fold stimulation at 10(-3) M H2O2. AA release induced by H2O2 was inhibited by the H2O2 scavenger catalase, but not by inactivated catalase or by scavengers of superoxide anion, hydroxyl radical, or ferric iron. An evaluation of cyclooxygenase metabolite formation by specific radioimmunoassays and high performance liquid chromatography demonstrated a greater than 2-fold increment in thromboxane (Tx)A2 (measured as TxB2) synthesis at 10(-4) M H2O2, but no increment in prostaglandin (PG) E2 synthesis. H2O2-induced TxB2 synthesis was cyclooxygenase-dependent, since it was inhibited by indomethacin (1 microM). There was no significant degradation of either PGE2 or TxB2 in AM cultures by H2O2 at concentrations to 10(-2) M. The effect of H2O2 on agonist-induced cyclooxygenase metabolism was also examined. H2O2 at 10(-4) M inhibited PGE2 synthesis induced by zymosan and A23187, whereas agonist-induced TxB2 synthesis was either unaffected (zymosan) or augmented (A23187) by H2O2. These findings suggest inhibition by H2O2 of PGE2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Rat alveolar macrophages synthesize leukotriene B4 and 12-hydroxyeicosatetraenoic acid from alveolar epithelial cell-derived arachidonic acid.

Although recent reports have described arachidonic acid metabolism of individual types of lung cells, the actual profile of eicosanoids that are produced in the lung may reflect interactions between different cell types. Because macrophages and epithelial cells are in close physical contact within the alveolus, we measured the eicosanoids produced by combined cultures of these cells. We found that the [14C]arachidonic acid that was released from previously labeled epithelial cells following A23187 stimulation was metabolized by alveolar macrophages to leukotriene B4 and 12-hydroxyeicosatetraenoic acid, which are products not normally produced by these epithelial cells. Simultaneously, there was a decrease in 6-keto-prostaglandin F1 alpha, the end product of prostacyclin metabolism and a major product of epithelial cell arachidonate metabolism but not macrophage arachidonate metabolism. A net increase in leukotriene B4 and a net decrease in 6-keto-prostaglandin F1 alpha were demonstrated by radioimmunoassay. Thus, the interaction of stimulated alveolar macrophages and epithelial cells alters the eicosanoid profile produced by each cell type alone in a manner that would tend to accentuate inflammatory processes within the alveolus.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Arachidonic acid metabolism in cultured alveolar macrophages from normal, atopic, and asthmatic subjects.

In order to test the hypothesis that alveolar macrophages (AM) from asthmatics might manifest abnormalities in the amounts, spectrum, or glucocorticoid regulation of eicosanoid synthesis, we compared arachidonic acid (AA) metabolism under resting and ionophore A23187-stimulated conditions in cultured AM obtained by bronchoalveolar lavage from 10 asthmatic, nine atopic, and 10 nonatopic normal subjects. [14C]AA-prelabeled AM constitutively released free [14C]AA and release increased significantly with A23187 incubation. Under resting conditions, unlabeled cells produced small amounts of immunoreactive thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4). With A23187 stimulation there were significant increases in the synthesis of all immunoreactive metabolites, which were produced in the following relative amounts: LTB4 much greater than TxB2 greater than PGD2 greater than leukotriene C4 greater than PGE2. High performance liquid chromatographic separation of radiolabeled eicosanoids produced by prelabeled cells confirmed the radioimmunoassay results and further indicated the production of relatively large amounts of 5-hydroxyeicosatetraenoic acid and 12-hydroxyheptadecatrienoic acid. Pretreatment (16 h) with 1 microM methylprednisolone inhibited A23187-induced synthesis of immunoreactive cyclooxygenase products to a greater extent than immunoreactive leukotrienes. We identified no significant differences among the three study groups in the quantities or profiles of eicosanoids synthesized either constitutively or with A23187 stimulation, nor in their regulation by methylprednisolone.

Adolescent↗
PubMed1988

Arachidonic acid metabolism by rat alveolar epithelial cells.

Arachidonic acid release and metabolism by stimulated cultures of rat type II alveolar epithelial cells (94 +/- 2% pure) were studied. As compared with unstimulated cultures, a marked increase in the release of [14C]arachidonic acid from prelabeled cells was observed when the cells were incubated with the calcium ionophore A23187. Radioimmunoassay of unlabeled cultures demonstrated significant increases in the production of prostaglandin E2 greater than 6-Keto-prostaglandin F1 alpha greater than prostaglandin F2 alpha greater than thromboxane B2 with A23187 stimulation. Reverse-phase high performance liquid chromatography of media from cells prelabeled with [14C]arachidonic acid confirmed the identities and relative amounts of these metabolites. As expected, the production of these cyclooxygenase products was inhibited by indomethacin. Stimulation with A23187 led to no increment in immunoreactive leukotriene C4 production, but yielded a statistically significant but quantitatively small increment in leukotriene B4 production; its production by small numbers of contaminating macrophages cannot be ruled out. Analysis by high performance liquid chromatography of media from prelabeled cells after 30 minutes stimulation revealed no peaks of radioactivity coeluting with the lipoxygenase products leukotriene B4, leukotriene C4, or 5-, 12-, or 15-hydroxy-6,8,11,14-eicosatetraenoic acid. The results indicate that rat alveolar epithelial cells have the capacity to release arachidonic acid and metabolize it to an array of cyclooxygenase products. However, after stimulation, little or no lipoxygenase products accumulated in media. Thus, the alveolar epithelium may be a source of bioactive eicosanoids with potentially important roles in pulmonary physiology and pathophysiology.

Animals↗
PubMed1987

Modulation of alveolar macrophage-derived 5-lipoxygenase products by the sulfhydryl reactant, N-ethylmaleimide.

The sulfhydryl reactant N-ethylmaleimide (NEM) stimulates the release and cyclooxygenase metabolism of arachidonic acid in rat alveolar macrophages. Because both 5-lipoxygenation and leukotriene (LT) C4 synthesis represent sulfhydryl-dependent steps in the 5-lipoxygenase pathway, we examined the effect of NEM on 5-lipoxygenase, as well as cyclooxygenase, metabolism in resting and agonist-stimulated cells by reverse-phase high performance liquid chromatography and radioimmunoassay. NEM at 5-10 microM stimulated the synthesis of thromboxane, but not prostaglandin E2 or the 5-lipoxygenase products LTC4, LTB4, or 5-hydroxyeicosatetraenoic acid from endogenously released arachidonate. In the presence of exogenous fatty acid, however, NEM stimulated the synthesis of large quantities of LTB4. The effect of NEM on arachidonate metabolism stimulated by the calcium ionophore A23187 and the particulate zymosan was also investigated. NEM augmented arachidonate release and thromboxane synthesis stimulated by A23187 but inhibited A23187-induced LTC4 synthesis with an IC50 of approximately 4.3 microM. This inhibitory effect closely paralleled the ability of NEM to deplete intracellular glutathione (IC50 approximately 4.3 microM). Preincubation with the intracellular cysteine delivery agent L-2-oxothiazolidine-4-carboxylate augmented intracellular glutathione concentration and A23187-stimulated LTC4 synthesis and attenuated the capacity of NEM to deplete glutathione and inhibit LTC4 synthesis. While LTB4 and 5-hydroxyeicosatetraenoic synthesis were unaffected at these low NEM concentrations, LTB4 synthesis was inhibited at high concentrations (IC50 approximately 210 microM). Zymosan-induced eicosanoid synthesis was modulated by NEM in a similar fashion. Thus, NEM is an agonist of arachidonate metabolism with the capacity to modulate the spectrum of macrophage-derived eicosanoids by virtue of specific biochemical interactions with substrates and enzymes of the 5-lipoxygenase pathway.

Animals↗
PubMed1987

Inhibition by methylprednisolone of zymosan-induced leukotriene synthesis in alveolar macrophages.

Alveolar-macrophage-derived 5-lipoxygenase metabolites of arachidonic acid (AA) are thought to be important mediators of lung inflammation and injury. Inhibition of AA metabolism may be an important anti-inflammatory mechanism of glucocorticoid (GC) action. In the present study, we have examined the effect of methylprednisolone (MP) on leukotriene (LT) B4 and LTC4 synthesis by cultured rat alveolar macrophages (AMs) stimulated with the proinflammatory particle zymosan. Zymosan stimulation resulted in the formation of LTB4 greater than thromboxane B2 (TxB2) greater than LTC4 as assessed by both high performance liquid chromatography and radioimmunoassay. Sixteen hours of pretreatment with 1 microM MP maximally inhibited synthesis of TxB2 by 76 +/- 4%, LTB4 by 83 +/- 3%, and LTC4 by 91 +/- 3%. The inhibition of eicosanoids was specific, as the sex hormones progesterone, testosterone, and beta-estradiol had no consistent effect. Inhibition was dose-dependent, with 50% inhibition of synthesis occurring at 10(-7) M for TxB2, but at 10(-8) M for both LTB4 and LTC4. Pretreatment with MP for only 1 h inhibited LTC4 production (42 +/- 3%) to a greater extent than either TxB2 (25 +/- 1%) or LTB4 (14 +/- 7%). These data indicate that MP significantly and substantially inhibits zymosan-induced LTB4 and LTC4 synthesis. Furthermore, the greater degree, greater potency, and faster onset of action for MP inhibition of LT synthesis than of TxB2 synthesis suggest the possibility that MP may exert postphospholipase effect(s) on LT synthesis. These results support the possibility that modulation of AM arachidonate metabolism may represent an important anti-inflammatory mechanism of GC action in the lung.

Animals↗
PubMed1985

Incidence of lung cancer in systemic sclerosis.

During a study of lung function in patients with systemic sclerosis, we followed 71 patients with this diagnosis for a mean of 5 years. During this period, 3 cases of lung cancer were observed in the group, giving a post hoc incidence of lung cancer of 8.6 cases/1000 persons/year compared to an expected incidence of 0.52 cases/1000 persons/year. The relative risk ratio for lung cancer in systemic sclerosis patients is 16.5. There was no definite association of lung cancer with cigarette smoking, but all 3 patients had either radiographic or pulmonary function evidence of interstitial pulmonary fibrosis. Although bronchoalveolar carcinoma is the most prevalent histologic type of lung cancer associated with systemic sclerosis in the reported cases in the literature, this was not present in any of our patients.

Female↗
PubMed1984

Carbon monoxide diffusing capacity as predictor of outcome in systemic sclerosis.

In order to determine the predictive value of lung function studies for subsequent prognosis in systemic sclerosis, 71 patients with systemic sclerosis were followed up for a mean of five years after pulmonary function testing. A carbon monoxide diffusing capacity less than or equal to 40 percent of the predicted reference value was associated with only a 9 percent five-year cumulative survival rate compared with a 75 percent cumulative five-year survival in patients with a carbon monoxide diffusing capacity greater than 40 percent of predicted. An obstructive ventilatory defect was also associated with increased mortality, and all six patients with obstruction and a diffusing capacity less than 70 percent of the predicted died during the study period. Male gender, independent of abnormalities of pulmonary function, was also associated with a poor prognosis. Although it is not clear whether a severely impaired diffusing capacity is indicative of interstitial pulmonary fibrosis or pulmonary vasculopathy or is a marker of generalized vascular disease, a severely depressed carbon monoxide diffusing capacity is an important predictor of mortality in patients with systemic sclerosis.

Actuarial Analysis↗
PubMed1984

Clinical and demographic predictors of loss of pulmonary function in systemic sclerosis.

The course of functional pulmonary involvement in systemic sclerosis remains controversial; and it is not known if specific clinical or demographic features are predictive of subsequent changes in pulmonary function. To address these questions, we conducted a non-concurrent prospective study of serial pulmonary function in 24 patients with systemic sclerosis unselected for pulmonary involvement over a mean follow-up interval of 59.7 months. Initial values for the entire group demonstrated a mild restrictive defect with a mild reduction in gas exchange. Although a restrictive pattern was most common, normal and obstructed pulmonary function were seen. Mean rates of change of FVC, TLC, FEV1/FVC, and Dco for the entire group were not different from normal, but substantial variability in the course of pulmonary functional involvement was seen among individuals. Changes in gas transfer, lung volumes, and airflow can occur independent of each other. Rates of change in pulmonary function were not predicted by initial pulmonary function, race, sex, duration of disease, cardiac involvement, roentgenographic fibrosis, or regression of skin disease. Patients with severe Raynaud' phenomenon exhibited the greatest fall in Dco over time, suggesting an association between peripheral and pulmonary vascular involvement. A correlation between exertional dyspnea and rapid loss of Dco was noted. Former smokers had significantly greater rates of loss of FVC and Dco than either non-smokers or current smokers, suggesting that cessation of smoking was a response to rapidly declining function in a subgroup of susceptible smokers. We detected a wide spectrum of severity of pulmonary prognosis in systemic sclerosis, ranging from normal pulmonary function to rapidly progressive disease leading to death. This study indicates that patients with prolonged survival do not necessarily have a rapidly progressive pulmonary component, but those with severe Raynaud's phenomenon and susceptible smokers are at very high risk for rapid deterioration of pulmonary function.

Adult↗
PubMed1984

Glucocorticoid inhibition of zymosan-induced arachidonic acid release by rat alveolar macrophages.

The phospholipase-dependent liberation of arachidonic acid (AA) from membrane phospholipids has been proposed as the rate-limiting step in the synthesis of bioactive AA metabolites, which play an important role in the expression of inflammatory and immune reactions. We have examined the effects of steroids in vitro on the release of AA by rat alveolar macrophages exposed to zymosan. Fluocinolone (1 microM) significantly inhibited the zymosan-induced release of radiolabeled AA from phosphatidylcholine as well as the production of radiolabeled prostaglandin E2. (PGE2). Dose-response curves gave the following rank order of potency: fluocinolone greater than dexamethasone greater than hydrocortisone. The maximal degree of inhibition of radiolabeled AA release observed was approximately 70%. Inhibition was not observed after 3 h of glucocorticoid pretreatment, but maximal inhibition was achieved after 10 h of pretreatment. Pretreatment with gonadal sex hormones (1 microM) did not inhibit AA release. Concurrent incubation of macrophages with hydrocortisone and excess concentrations of the partial glucocorticoid agonist, progesterone, blunted the degree of inhibition observed with hydrocortisone alone. These data are consistent with a receptor-mediated process. The time course suggests a response dependent on new protein synthesis, and the increased concentration of the phospholipase-inhibitory protein, lipomodulin, in steroid-treated cultures is putative evidence of new protein synthesis.

Animals↗
PubMed1978

Pathologic changes in the lungs of oxygen-adapted rats: a morphometric analysis.

Animals exposed to 85 per cent O2 for 5 or more days acquire the ability to survive for prolonged periods in 100 per cent O2. The basis of this acquired "tolerance" is poorly understood, but it has been proposed to be related to biochemical changes occurring in the lung cells. In order to quantify the structural changes that occur in the lungs of oxygen-adapted rats, rats were exposed to 85 per cent O2 for 7 days and then studied using morphometric techniques. The oxygen-adapted rats had a normal number of alveolar type I epithelial cells and a moderate increase in the number of alveolar type II cells. The alveolar type I epithelium was intact over the entire alveolar surface and appeared to have a normal ultrastructure, whereas alveolar type II cells demonstrated occasional changes in mitochondrial structure. In the interstitial compartment, there was a large increase in the number of interstitial cells and a significant increase in the noncellular components of the interstitium. The major area of pulmonary damage occurred in the vascular compartment, where entire segments of the capillary bed were lost and the total number of endothelial cells decreased by 45 per cent. A significant change in pulmonary vascular hemodynamics was suggested by a 49 per cent decrease in total capillary lumen volume and a decrease in the hematocrit of blood in the pulmonary capillary lumen to 57 per cent of the value found in aortic blood.

Adaptation, Physiological↗