Lung deflation impairs alveolar epithelial fluid transport in ischemic rabbit and rat lungs.

BACKGROUND: Because the fluid transport capacity of the alveolar epithelium after lung ischemia with and without lung deflation has not been well studied, we carried out experimental studies to determine the effect of lung deflation on alveolar fluid clearance. METHODS: After 1 or 2 hr of ischemia, we measured alveolar fluid clearance using 125I-albumin and Evans blue-labeled albumin concentrations in in vivo rabbit lungs in the presence of pulmonary blood flow and in ex vivo rat lungs in the absence of any pulmonary perfusion, respectively. RESULTS: The principal results were: (1) lung deflation decreased alveolar fluid clearance while inflation of the lungs during ischemia preserved alveolar fluid clearance in both in vivo and ex vivo studies; (2) alveolar fluid clearance was normal in the rat lungs inflated with nitrogen (thus, alveolar gas composition did not affect alveolar fluid clearance); (3) amiloride-dependent alveolar fluid clearance was preserved when the lungs were inflated during ischemia; (4) terbutaline-simulated alveolar fluid clearance was preserved in the hypoxic rat lungs inflated with nitrogen; (5) lecithinized superoxide dismutase, a scavenger of superoxide anion, and N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide, preserved normal alveolar fluid clearance in the deflated rat lungs. CONCLUSION: Lung deflation decreases alveolar fluid clearance by superoxide anion- and nitric oxide-dependent mechanisms.

Airway pressure-volume curve estimated by flow interruption during forced expiration.

We attempted to estimate the pressure-volume characteristics of airways downstream from the choke point when the airflow was abruptly interrupted during forced expiration. The change of gas volume of the downstream segment after interruption could be estimated by multiplying the maximum flow (Vmax) immediately before interruption by the interruption time because the Vmax is maintained for a short period after airflow interruption at the mouth, as described in our previous report (J. Appl. Physiol. 66: 509-517, 1989). For the pressure of the downstream segment, we used the mouth pressure itself. Airway compliance, a slope of the pressure-volume curve, was measured in an airway model in eight normal subjects, in six patients with chronic obstructive pulmonary disease (COPD), and in one patient with tracheobronchopathia osteochondroplastica. Airway compliance was 0.96 ml/cmH2O in normal subjects and 2.49 ml/cmH2O in COPD patients. This difference of airway compliance was believed to be caused by the longitudinal expansion of the downstream segment and changes in the properties of the airway wall.

Mouth pressure curve on abrupt interruption of airflow during forced expiration.

An attempt was made to investigate how the mouth pressure curve represents the process of air flowing into the collapsed segment downstream to the choke point when the airflow is abruptly interrupted at the mouth during forced expiration. Immediately after the interruption of airflow, the mouth pressure suddenly increased (phase 1), followed by a slower rise in pressure (phase 2) within approximately 100 ms until the pressure reached the alveolar pressure. The pleural and alveolar pressures remained constant during this process. The first phase of the abrupt rise represented the pressure induced by the instantaneous interruption of the airflow itself. Analysis of the supramaximal flow (Vsupramax) observed after resumption of the airflow suggested that the choke point remained constant during the second phase of the mouth pressure after interruption of maximal flow (Vmax). From these results, examination of the second phase of the mouth pressure curve may provide useful information about the downstream segment of the airway.

Vascular effects of platelet-activating factor in lambs: role of cyclo- and lipoxygenase.

In adult sheep, platelet-activating factor (PAF) effects include systemic hypotension and pulmonary hypertension. To identify developmental differences in vascular responses to PAF, we studied the effects of C18- and C16-PAF in 49 +/- 2- (SE) day-old lambs. Responses of upstream (arteries and microvessels) and venous segments of the lung to C18-PAF were determined both in vivo and in isolated lungs. In isolated lungs, the role of eicosanoids in PAF effects was also determined. In vivo, both C18- and C16-PAF caused a significant increase in systemic and pulmonary vascular resistance. The magnitude of vascular responses to C16-PAF was greater than that to C18-PAF. C18-PAF constricted both upstream and venous segments of the pulmonary circulation. Cyclooxygenase inhibition in isolated lungs attenuated arterial constriction to C18-PAF, whereas simultaneous cyclooxygenase and lipoxygenase inhibition completely blocked the effects of C18-PAF. In summary, in contrast to PAF effects in adult sheep, PAF constricts both systemic and pulmonary vessels in lambs, with significant pulmonary venous constriction. Eicosanoids, especially lipoxygenase products, play a major role in mediating PAF effects in the lung.

A new nasal acoustic reflection technique to estimate pharyngeal cross-sectional area during sleep.

The conventional acoustic reflection technique in which acoustic waves are launched through the mouth cannot be applied during sleep, nor can it be applied to the nasopharynx, which is the major site of occlusion in patients with obstructive sleep apnea syndrome. We propose a new technique of nasal acoustic reflection to measure pharyngeal cross-sectional areas including the nasopharynx. The acoustic waves are introduced simultaneously to both nostrils during spontaneous nasal breathing. A new algorithm takes into account the nasal septum with asymmetric nasal cavities on both sides and assumes prior knowledge of the cross-sectional area of the nasal cavities and the position of the nasal septum. This method was tested on an airway model with a septum and on healthy human subjects. The conventional technique gave inaccurate measurements for pharyngeal cross-sectional areas for an airway model with asymmetric branching, whereas the new technique measured them almost perfectly. The oro- and hypopharyngeal cross-sectional area measurements acquired by the new method were not different from those obtained by the conventional method in normal subjects. This new method can be used as a monitor of upper airway dimensions in nocturnal polysomnography.

Denopamine, a beta(1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs.

The effect of denopamine, a selective beta(1)-adrenergic agonist, on alveolar fluid clearance was determined in both ex vivo rat and guinea pig lungs. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue-labeled albumin over 1 h at 37 degrees C. Denopamine (10(-6) to 10(-3) M) increased alveolar fluid clearance in a dose-dependent manner in ex vivo rat lungs. Denopamine also stimulated alveolar fluid clearance in guinea pig lungs. Atenolol, a selective beta(1)-adrenergic antagonist, and amiloride, a sodium channel inhibitor, inhibited denopamine-stimulated alveolar fluid clearance. The potency of denopamine was similar to that of similar doses of isoproterenol or terbutaline. Short-term hypoxia (100% nitrogen for 1-2 h) did not alter the stimulatory effect of denopamine. Denopamine (10(-4), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate levels in cultured rat alveolar type II cells. In summary, denopamine, a selective beta(1)-adrenergic agonist, stimulates alveolar fluid clearance in both ex vivo rat and guinea pig lungs.

Effect of pulmonary blood flow on microvascular pressure profile determined by micropuncture in perfused cat lungs.

To clarify the role of the pulmonary microvasculature in adjusting to increased pulmonary blood flow, we measured arteriolar and venular pressure by the servo-null micropuncture method while changing the pulmonary blood flow in isolated perfused cat lungs. We divided the lung vasculature into three longitudinal segments: 1) arterial (pulmonary artery to 30- to 50-microns arteriole), 2) microvascular (between 30- to 50-microns arteriole and venule), and 3) venous (30- to 50-microns venule to left atrium). The vascular resistance was calculated by dividing the pressure gradient by the flow. The pressure gradient of the microvascular segment did not increase, whereas the pressure gradient of the arterial and venous segments increased simultaneously with flow rate. Total and microvascular resistance decreased with increase of flow rate. Resistances of the arterial and venous segments did not change with increase in flow. We conclude that the microvasculature plays a crucial role in preventing pulmonary hypertension with increases in flow by decreasing microvascular resistance.

Effects of hypoxia on alveolar fluid transport capacity in rat lungs.

There is little information regarding the effect of hypoxia on alveolar fluid clearance capacity. We measured alveolar fluid clearance, lung water volume, plasma catecholamine concentrations, and serum osmolality in rats exposed to 10% oxygen for up to 120 h and explored the mechanisms responsible for the increase in alveolar fluid clearance. The principal results were 1) alveolar fluid clearance did not change for 48 h and then increased between 72 and 120 h of exposure to hypoxia; 2) although nutritional impairment during hypoxia decreased basal alveolar fluid clearance, endogenous norepinephrine increased net alveolar fluid clearance; 3) the changes of lung water volume and serum osmolality were not associated with those of alveolar fluid clearance; 4) an administration of beta-adrenergic agonists further increased alveolar fluid clearance; and 5) alveolar fluid clearance returned to normal within 24 h of reoxygenation after hypoxia. In conclusion, alveolar epithelial fluid transport capacity increases in rats exposed to hypoxia. It is likely that a combination of endogenous norepinephrine and nutritional impairment regulates alveolar fluid clearance under hypoxic conditions.

Effect of hypoxia on pulmonary blood flow-segmental vascular resistance relationship in perfused cat lungs.

To investigate the effect of alveolar hypoxia on the pulmonary blood flow-segmental vascular resistance relationship, we determined the longitudinal distribution of vascular resistance while increasing blood flow during hyperoxia or hypoxia in perfused cat lungs. We measured microvascular pressures by the micropipette servo-null method, partitioned the pulmonary vessels into three segments [i.e., arterial (from main pulmonary artery to 30- to 50-micron arterioles), venous (from 30- to 50-micron venules to left atrium), and microvascular (between arterioles and venules) segments] and calculated segmental vascular resistance. During hyperoxia, total resistance decreased with increased blood flow because of a reduction of microvascular resistance. In contrast, during hypoxia, not only microvascular resistance but also arterial resistance decreased with increase of blood flow while venous resistance remained unchanged. The reduction of arterial resistance was presumably caused by arterial distension induced by an elevated arterial pressure during hypoxia. We conclude that, during hypoxia, both microvessels and arteries >50 micron in diameter play a role in preventing further increases in total pulmonary vascular resistance with increased blood flow.

[Pulmonary aspergilloma clearly demonstrated by digital subtraction bronchography].

A 69-year-old woman was admitted because of persistent productive cough, low-grade fever and abnormal pulmonary infiltrates. Chest roentgenograms revealed right pulmonary cavitary lesions and infiltrates in both upper pulmonary fields. Digital subtraction bronchography (DSBG) was performed to detect for the presence of pulmonary cavitary lesions. Double-contrast DSBG images clearly revealed marked bronchiectasis in the right pulmonary cavity with aspergilloma in the cavitary lesions. Aspergilloma was not obvious in routine chest roentgenograms and computed tomograms. Asperillus fumigatus was cultured from sputum materials, and aspergilloma of the pulmonary cavity was clinically diagnosed. The infiltrative lesions were thought to be associated with invasive aspergillosis because the patient exhibited persistent low-grade fever and positive inflammatory reactions. Anti-fungal chemotherapy was highly effective in treating these lesions. DSBG is a new, less-invasive bronchographic technique for the evaluation of bronchial trees, and in this case proved useful for the detection of small aspergilloma in pulmonary cavities.

[Pulmonary metastatic malignant phyllodes tumor showing multiple thin walled cavities].

A 52-year-old woman who had undergone a partial mastectomy 1 year earlier because of benign phyllodes tumor was admitted because of dry cough and abnormal chest radiograph findings. Chest computed tomograms demonstrated multiple thin-walled cavities and nodules. Clinical examinations and transbronchial biopsy specimens failed to provide a conclusive diagnosis. However, the pulmonary thin-walled cavities enlarged, and a nodular shadow revealed cavitary formation. An open lung biopsy was performed to diagnose the pulmonary lesions. Although biopsy specimens disclosed the infiltration of poorly differentiated adenocarcinoma cells in pleura and pulmonary parenchyma, no primary site was detected. The patient did not respond to systemic chemotherapy (CDDP and VP-16), and died of respiratory failure due to advanced pulmonary metastasis. Autopsy demonstrated marked tumor invasion of the lungs, myocardium, and bone. We analyzed malignant cells in lung tissues at autopsy by immunohistochemistry, and found identical malignant cells in surgical samples obtained during the patients earlier mastectomy. A diagnosis of pulmonary metastasis from malignant phyllodes tumor of the breast was made. Thin walled cavitary lesions from malignant phyllodes tumor are rare; however, pulmonary metastasis of malignant phyllodes tumor should be considered one disease that exhibits thin-walled cavities as a radiographic manifestation.

[Lung tissue injury caused by oxidant-antioxidant imbalance].

The lung is susceptive to excess oxidants from inhaled air and marginated large portion of circulating leukocytes. Oxygen radicals generated from sequestrated leukocytes injure endothelial cells to increase permeability. Excessively generated oxidants in the mitochondria, such as in ischemia-reperfusion injury, changes mitochondrial function and cause Ca++ leak from the organelle, which leads to induction of apoptosis. Reactive oxygen intermediates induce some cytokine gene expression such as IL-8. Hydrogen peroxide activates phospholipase C and the subsequent signal transduction pathways resulting in change of cytoskeletal configuration and cell shape. It is expected that understanding of contribution of oxidant-antioxidant imbalance in lung diseases may develop new strategy of 'antioxidant' therapies.

Sleep apnoea syndrome as a risk for mortality in elderly inpatients.

OBJECTIVE: The characteristics of sleep apnoea syndrome (SAS) in the elderly, including subtype classification and association with mortality, have not been fully elucidated. This study examined these factors in an elderly Japanese inpatient population. METHODS: Overnight polysomnography was used to diagnose and classify SAS in 145 elderly inpatients (mean ± age 81 ± 8 years). Clinical data, including brain computerized tomography findings, were recorded. The study population included nine inpatients with obstructive SAS, 12 with central SAS, 25 with mixed SAS and 99 controls (no SAS). RESULTS: Increased body mass index and grade of aortic arch calcification independently contributed to risk of all subtypes of SAS combined. There was an independent association between SAS and increased risk of mortality from all causes as well as from pneumonia and from cardiovascular disease. Only mixed SAS was independently and positively associated with increased risk of death from pneumonia. CONCLUSIONS: Obstructive, central and mixed SAS were associated with increased risk of cardiovascular related and all-cause mortality. Mixed SAS was associated with an increase in mortality from pneumonia. There was no relationship between mortality and severity of SAS.

Mouth pressure curve on abrupt interruption of airflow during forced expiration.

The mouth pressure curve after abrupt interruption during forced expiratory maneuver was investigated to evaluate the collapsing state of the airway downstream to the choke point. Immediately after the airflow interruption at the mouth by means of the electromagnetic valve, the mouth pressure suddenly increased (1st phase), followed by a slower rise (2nd phase) within about 100 msec until the pressure reaches the alveolar pressure. The pleural and alveolar pressures remained constant during this process. It was evidenced that, from point of view of mean flow, the airflow flowed at a rate of Vmax through the choke point during the second phase. Thus, it is strongly suggested that the choke point remained at the same point during the 2nd phase. From these results, the 2nd phase of the mouth pressure is expected to represent the specific characteristics for the downstream airway.