Treatment of smoke-induced pulmonary injury with nebulized dimethylsulfoxide

Inhalation injury was produced in sheep that were chronically prepared for study. The injury was induced by insufflating them with smoke from burning cotton cloth. One group of animals was treated with the oxygen-free radical scavenger dimethylsulfoxide (DMSO) and heparin. Another group received heparin treatment alone, and a third was untreated. The drugs were nebulized into the tracheostomy at 4-hr intervals beginning 1 hr after injury. Following the inhalation injury, lung lymph flow and extravascular lung water measured by thermal-dye dilution technique were both increased. These elevations were associated with minor increases in pulmonary artery pressure, and, thus, since the lymph to plasma protein ratio was unchanged, this increased extravascular fluid formation was probably the result of an elevated microvascular permeability. These changes were associated with a reduction in alpha 2 macroglobulin antiprotease activity. The treated groups showed much smaller responses to the inhalation insult. This was especially true in the animals that received the DMSO. These findings support the concept that oxygen free radicals are responsible for the pulmonary edema associated with inhalation injury.     

Ibuprofen reduces the lung lymph flow changes associated with inhalation injury

Inhalation injury was produced in sheep which were chronically prepared for study. The injury was induced by insufflating them with smoke from burning cotton cloth. One group of animals was treated with the cyclooxygenase inhibitor ibuprofen and another group was untreated. Eight hr following the administration of smoke, there was an elevation of lung lymph flow in both groups. These changes were not as severe in the animals which were treated with ibuprofen. The pulmonary changes which occur following smoke inhalation injury are associated with elevations of the metabolites of arachidonic acid, especially those generated by the cyclooxygenase pathway. These metabolites in some way contribute to the pathophysiological changes induced by the inhalation of smoke, since they are reduced by the administration of a cyclooxygenase inhibitor.     

Inhalation injury and positive pressure ventilation in a sheep model

The mortality rate of inhalation injury was lowered in six chronically instrumented sheep through positive pressure ventilation and positive end-expiratory pressure (PEEP). Six range ewes were prepared for study by implanting catheters to measure lung lymph flow and cardiopulmonary variables. After surgery, these animals were studied in the unanesthetized state and then subjected to an inhalation by insufflating them with smoke from burning cotton. Following the smoking procedure, the animals were studied for 72 hr. All had marked falls in arterial oxygen tension and they developed dyspnea within 24 hr. The inhalation injury produced a marked change in lung lymph flow concomitant with an elevation in the lymph to plasma (L/P) oncotic pressure ratio. This is characteristic of a change in microvascular permeability to protein. A tracheostomy was performed at 72 hr and the animals were connected to positive pressure ventilators with PEEP. All six animals survived. It was concluded that the sheep lung lymph preparation is a very suitable model for the study of inhalation injury and positive pressure ventilation.     

吸入一氧化氮对犬烟雾吸入性损伤肺组织ACE活性的影响

血管紧张素转换酶（ACE）已作为肺毛细血管内皮细胞受损的指示性指标，本研究旨在评价吸入一氧化氮（NO）对吸入性损伤后肺血管内皮细胞的影响。用21只犬随机分为3组，烟雾吸入后，吸氧组（n=8）单纯吸氧（FiO2，0．45）；NO治疗组（n=9）吸氧（FiO2，0．45）＋0．0045％（45PPm）NO，连续监测12小时动脉血ACE活性变化；正常组（n＝4）不致伤，用于建立组织学对照。动脉血数据行多个样本均数间方差分析，支气管肺泡灌洗液（BALF）和肺组织ACE活性行两样本均数t检验。结果治疗组血浆ACE活性比对照组降低（P＜0．05）；BALF和肺组织中，治疗组ACE活性也明显低于对照组（P＜0．01）。吸入NO对犬烟雾吸入性损伤肺毛细血管内皮细胞有一定减轻损害作用。     

Equilibration of intravascular albumin with lung lymph in unanesthetized sheep

In 16 unanesthetized sheep with chronic lung lymph fistulas we measured pulmonary vascular pressures, lymph flow, lymph and plasma total protein and albumin concentration. We determined the rate of equilibration of radioiodinated albumin between plasma and lung interstitial fluid (lung lymph) in three steady-state conditions; baseline (n = 14), increased pulmonary microvascular pressure (n = 9) and increased microvascular permeability (n = 4). The tracer protein equilibration proceeded according to single compartment wash-in kinetics in all experiments. Lung lymph flow averaged 5.3 +/- 2.8 (S.D.)ml/h under baseline conditions, 16.1 +/- 10.6 ml/h during increased pressure and 37.3 +/- 29.4 ml/h during increased permeability. The half time of equilibration averaged 2.9 +/- 1.0 h, 2.2 +/- 1.0 h and 0.7 +/- 0.2 h, respectively. Lung interstitial fluid equilibrates with plasma proteins more rapidly than most other organs. The marked difference between increased permeability and the other conditions demonstrates the sensitivity of this method. No evidence was obtained that any tracer protein entered lung lymph within the caudal mediastinal lymph node.     

Ibuprofen prevents synthetic smoke-induced pulmonary edema

Multiple potentially injurious agents are present in smoke but the importance of each of these agents in producing lung injury as well as the mechanisms by which the lung injury is produced are unknown. In order to study smoke inhalation injury, we developed a synthetic smoke composed of a carrier of hot carbon particles of known size to which a single known common toxic agent in smoke, in this case HCI, could be added. We then exposed rats to the smoke, assayed their blood for the metabolites of thromboxane and prostacyclin, and intervened shortly after smoke with the cyclooxygenase inhibitors indomethacin or ibuprofen to see if the resulting lung injury could be prevented. Smoke exposure produced mild pulmonary edema after 6 h with a wet-to-dry weight ratio of 5.6 +/- 0.2 SEM (n = 11) compared with the non-smoke-exposed control animals with a wet-to-dry weight ratio of 4.3 +/- 0.2 (n = 12), p less than 0.001. Thromboxane B, and 6-keto-prostaglandin F1 alpha rose to 1,660 +/- 250 pg/ml (p less than 0.01) and to 600 +/- 100 pg/ml (p greater than 0.1), respectively, in the smoke-injured animals compared with 770 +/- 150 pg/ml and 400 +/- 100 pg/ml in the non-smoke-exposed control animals. Indomethacin (n = 11) blocked the increase in both thromboxane and prostacyclin metabolites but failed to prevent lung edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.     

High MW hyaluronan inhibits smoke inhalation‐induced lung injury and improves survival

Background and objective: High MW hyaluronan (HMW HA) as opposed to low MW hyaluronan (LMW HA) has been shown to have anti‐inflammatory and anti‐apoptotic effects. We hypothesized that treatment with HMW HA would block smoke inhalation lung injury by inhibiting smoke‐induced lung inflammation and airway epithelial cell apoptosis. Methods: Anesthetized, intubated male rats were randomly allocated to either control or smoke inhalation injury groups. Rats were treated with 3‐mL subcutaneous normal saline solution (sham) or LMW HA (35 kDa) or HMW HA (1600 kDa) 18 h before exposure to 15 min of cotton smoke (n = 5 each). Rats were also treated post smoke inhalation with 1600 kDa HA by intra‐peritoneal injection (3 mL) or intra‐tracheal nebulization (200 µL). Lung neutrophil infiltration, airway apoptosis, airway mucous plugging and lung injury were assessed 4 h after smoke inhalation injury. Results: Rats pretreated with 1600 kDa HA had significantly less smoke‐induced neutrophil infiltration, lung oedema, airway apoptosis and mucous plugging. Pretreatment with 35 kDa HA, in contrast, increased smoke‐induced neutrophil infiltration and lung injury score. Intra‐tracheal administration of a single dose 1600 kDa HA, but not intra‐peritoneal injection, significantly improved survival post smoke inhalation. Conclusions: High MW hyaluronan (1600 kDa) may prove to be a beneficial therapy for smoke inhalation through inhibition of smoke‐induced inflammation, lung oedema, airway epithelial cell apoptosis and airway mucous plugging.     

烟雾吸入伤后血管紧张素转化酶的变化及意义

采用大鼠烟雾吸入伤模型，动态观察了伤后支气管肺泡灌洗液（BALF）及血浆中血管紧张素转化酶（ACE）活性的变化，辅以动脉血气分析，肺水量及BALF中总蛋白和白蛋白含量测定。结果发现，动物伤后出现急性呼吸衰竭和严重肺水肿，BALF中总蛋白和白蛋白含量均显著增加；血浆及BALF中ACE活性亦明显升高，且与BALF中蛋白水平的变化明显相关，提示ACE不仅是吸入伤后血管内皮细胞损伤的标志，而且可作为血管通透性增加及诊断严重吸入性损伤的早期敏感指标。     

Superoxide dismutase prevents the thrombin-induced increase in lung vascular permeability: role of superoxide in mediating the alterations in lung fluid balance

We investigated the effects of superoxide dismutase (SOD) and SOD linked to Ficoll (mol. wt = 400,000) on the changes in pulmonary transvascular fluid and protein exchange following pulmonary microembolism induced with alpha-thrombin. Studies were made in chronically prepared unanesthetized sheep with lung lymph fistulas. Control thrombin challenged sheep (n = 5) were compared to animals infused with SOD (the SOD-thrombin group, n = 5) or animals infused with SOD linked to high molecular weight Ficoll (the Ficoll-SOD-thrombin group, n = 6). The Ficoll-SOD-thrombin animals were also compared to animals infused with Ficoll alone (the Ficoll-thrombin group, n = 4). In the control-thrombin group, thrombin induced sustained increases in the pulmonary transvascular protein clearance (pulmonary lymph flow X lymph/plasma protein concentration ratio) and pulmonary vascular resistance (PVR). In the SOD-thrombin group, thrombin initially increased both pulmonary transvascular protein clearance and PVR; however, the later increases in protein clearance and PVR were blunted. The pulmonary reflection coefficients for total protein (sigma), a measure of vascular permeability to protein, decreased from a value of 0.70 +/- 0.03 in normal sheep to 0.60 +/- 0.01 following thrombin challenge (p less than 0.05) indicating an increase in lung vascular permeability. The sigma value in the SOD-treated animals was 0.70 +/- 0.02, indicating a protective effect of SOD. The infusion of the Ficoll-SOD complex also attenuated the increases in pulmonary transvascular protein clearance and PVR after thrombin. However, the infusion of Ficoll alone induced a similar protection. The lymph from the SOD-thrombin and Ficoll-SOD-thrombin groups prevented the reduction of ferricytochrome C by xanthine/xanthine oxidase, whereas, the lymph from the Ficoll-thrombin animals did not have this effect, indicating SOD activity was present in the animals receiving the enzyme but not in the group infused with Ficoll alone. Differences in the degree of intravascular coagulation could not explain the response to Ficoll since the decreases in fibrinogen concentration following the thrombin were similar in all the groups. Since Ficoll and related dextrans may modify neutrophil function, in particular neutrophil adherence to the endothelium, we examined the effects of Ficoll on neutrophil adherence. The results indicated that when Ficoll was added to the endothelial medium Ficoll reduced the increase adherence of neutrophils to the endothelial cell monolayer. Therefore, Ficoll as a carrier for SOD may provide a direct protection in models of lung vascular injury that are dependent on neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)     

Attenuation of reperfusion-induced systemic inflammation by preconditioning with nitric oxide in an in situ porcine model of normothermic lung ischemia

STUDY OBJECTIVES: Inhalation of nitric oxide (NO) can ameliorate pulmonary ischemia/reperfusion (I/R) injury of the lung in several experimental models, but toxic effects of NO were also reported. Here we investigate whether NO inhalation for a short period prior to surgery is sufficient to prevent symptoms of lung I/R injury, especially the inflammatory response. DESIGN: Using an in situ porcine lung model, normothermic left lung ischemia was maintained for 90 min, followed by a 5-h reperfusion period (group 1, n = 7). In group 2 (n = 6), I/R was preceded by inhalation of NO (10 min, 15 ppm). Animals in group 3 (n = 7) underwent sham surgery without NO inhalation or ischemia. MEASUREMENTS: Oxygenation and hemodynamic parameters were measured as indicators of lung functional impairment. Plasma levels of interleukin (IL)-1beta, IL-6, and transforming growth factor (TGF)-beta1 were determined throughout the I/R maneuver. In addition, tissue macrophages were analyzed by lectin binding. RESULTS: Symptoms of I/R injury (pulmonary hypertension and decreased oxygenation) in group 1 animals were attenuated by NO inhalation. The reperfusion-induced increases of the levels of IL-1beta and IL-6 in plasma were reduced by NO pretreatment. A peak of TGF-beta1 immediately after NO administration was observed in group 2, but not in groups 1 and 3. There was no significant effect of NO on tissue macrophages. CONCLUSION: NO inhalation for a short period prior to lung I/R is sufficient to protect against pulmonary hypertension, impaired oxygenation, and the inflammatory response of pulmonary I/R injury.     

Effect of crystalloid resuscitation and inhalation injury on extravascular lung water: clinical implications

STUDY OBJECTIVE: Arterial thermal dilution with an integrated fiberoptic monitoring system (COLD Z-021; Pulsion Medical Systems; Munich, Germany) allows measurement of extravascular lung water (EVLW) and pulmonary permeability index (PPI). The aim of this study was to evaluate the widespread clinical assumption that early respiratory failure following burn and inhalation injury is due to interstitial fluid accumulation in the lung. DESIGN: Clinical, prospective study. SETTING: ICU of a university referral center of burn care. PATIENTS: Thirty-five severely burned adults (> 20% of body surface area). INTERVENTIONS: Resuscitation therapy was guided by the results of hemodynamic monitoring using the intrathoracic blood volume (ITBV) as a cardiac preload indicator. The resuscitation goals included a normalization of preload (ITBV > 850 mL/m(2)) and cardiac index (> 3.5 L/min/m(2)) within 24 h after ICU admission. Fluid loading was implemented to reach these goals. MEASUREMENTS AND RESULTS: One hundred forty lung water measurements were performed at 0 h, 12 h, 24 h, and 48 h after admission to the ICU. Significant elevation of EVLW and PPI was found in three measurements (2%) at 48 h after ICU admission, and was in one patient associated with inhalation injury. EVLW and PPI were not significantly different between patients with and without inhalation injury. No correlation was found between resuscitation volume and EVLW (r(2) = 0.02) or between the alveolar-arterial oxygen pressure difference and EVLW (r(2) = 0.017). Chest radiograph abnormalities were found in 2 of 22 patients with inhalation injury; these were not associated with increased values of EVLW. CONCLUSION: Early fluid accumulation in the lung in burned patients is very uncommon, even in the presence of inhalation injury. There is no evidence that thermal injury causes an increase in pulmonary capillary membrane permeability.     

Dose Dependence and Time Course of Smoke Inhalation Injury in a Rabbit Model

The dose dependence and time course of smoke inhalation injury were determined in a rabbit model. Animals were insufflated with 18–90 breaths of cotton smoke or room air (control) at a rate of 18 breaths/min and tidal volume of 12 ml/kg. Smoke-exposed animals exhibited dose-related histologic effects with progressive deterioration of respiratory function during the postexposure period of observation (96 h). The smoke-exposed rabbits had reproducible injuries to both airway mucosa and lung parenchyma, manifested by disruption and sloughing of airway and alveolar epithelia, and exudation of protein-rich fluid and leukocytes into the airway and alveolar spaces. Significant effects were evident by 24 h postexposure. Smoke inhalation also affected the respiratory burst of alveolar macrophages. Generation of superoxide anions by alveolar macrophages at 48 h postexposure was increased significantly after smoke inhalation (54 breaths). The present rabbit model should be useful for studying the interactions between pulmonary epithelial cells and leukocytes after smoke inhalation and for determining the role that abnormal functioning of alveolar macrophages plays in the development of smoke inhalation injury. Accepted for publication: 8 October 1998     

Chronic cigarette smoke inhalation and aging in mice: 1. Morphologic and functional lung abnormalities

The effects of long-term cigarette smoke inhalation on the morphologic and functional integrity of lungs of C57BL/6 young and old mice have been assessed. Smoke exposure occurred over a 9-month period beginning when the young animals were 2 months of age and the old mice 8-10 months. At the termination of the experiment, microscopic and morphometric evaluation of pulmonary tissue revealed peribronchiolar and perivascular accumulations of lymphocytes and macrophages in lungs of both young and old smoke-exposed mice. Such lesions were never observed in sham-treated or control animals of either age. These observations indicate that lesions in mice can be induced by long-term smoke inhalation. In addition, three other anomalous manifestations, prominent only in the smoke-exposed old animals, were noted: 1) reduction of alveolar space with a concomitant increase in lung cellularity and thickened alveolar septa; 2) intra-alveolar accumulation of surfactantlike material; and 3) decreased pulmonary function. Since these abnormalities were prominent only in smoke-exposed old animals, an interaction between smoke inhalation and aging is indicated. Pulmonary function data complement morphologic and morphometric observations and indicate that the manifestation of abnormality noted in the old smoke-exposed animals are restrictive in nature and conform most closely to pulmonary fibrosis.     

Combined monitoring of thoracic duct and lung lymph during E. coli sepsis in awake sheep

A thoracic duct lymph fistula in combination with a lung lymph fistula in the awake sheep was used to evaluate effects of thoracic lymph diversion during a septic insult and to monitor systemic and local changes in the lung and gastrointestinal tract. Live Escherichia coli 10(9) kg-1 b.w. were infused in 9 sheep. After sepsis, arterial pressure, cardiac output, partial pressure of oxygen, leukocytes and platelets decreased significantly compared to baseline values. Pulmonary arterial pressure increased significantly throughout the experiment with peak values at 44 +/- 4 mmHg after 15 minutes. Lung lymph flow (QL) (n = 6) increased from 23 +/- 0.5 to 11.2 +/- 2.4 ml/30 minutes after 60 minutes. QL then decreased but remained elevated. Lymph to plasma protein concentration ratio (L/P) in lung lymph decreased from 0.62 +/- 0.02 during baseline to 0.47 +/- 0.04 after 60 minutes. L/P then increased and was, after 150 minutes, no longer different from baseline. These lung lymph data favor increased pulmonary microvascular permeability during sepsis. Lymph flow in the thoracic duct (QT) (n = 9) increased from 34.2 +/- 6 to 58.3 +/- 9 ml/30 minutes during the first 30 minutes after bacterial infusion. QT was, after 90 minutes, back to baseline but then progressively increased. L/P in thoracic lymph steadily increased from 0.56 +/- 0.03 to 0.78 +/- 0.04. Thromboxane B2 and 6-keto PGF1 alpha in thoracic duct and lung lymph increased significantly after bacterial infusion and remained elevated thereafter. Combined monitoring of thoracic duct and lung lymph enabled comparison of systemic and pulmonary reactions in septic sheep.     

The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury

In this study we examined the role of inducible nitric oxide synthase (iNOS) in acute respiratory distress syndrome (ARDS) in sheep with severe combined burn and smoke inhalation injury. BBS-2, a potent and highly selective iNOS dimerization inhibitor, was used to exclude effects on the endothelial and neuronal NOS isoforms. Seven days after surgical recovery, sheep were given a burn (40% of total body surface, 3rd degree) and insufflated with cotton smoke (48 breaths, < 40 degrees C) under anesthesia. BBS-2 was provided by constant infusion at 100 microg/kg/hour, beginning 1 hour after injury. During 48 hours, control sheep developed multiple signs of ARDS. These included decreased pulmonary gas exchange, increased pulmonary edema, abnormal lung compliance, and extensive airway obstruction. These pathologies were associated with a large increase in tracheal blood flow and elevated plasma NO2-/NO3- (NOx) levels. These variables were all stable in sham animals. Treatment of injured sheep with BBS-2 attenuated the increases in tracheal blood flow and plasma NOx levels, and significantly attenuated all the pulmonary pathologies that were noted. The results provide definitive evidence that iNOS is a key mediator of pulmonary pathology in sheep with ARDS resulting from combined burn and smoke inhalation injury.     

Ethchlorvynol-induced pulmonary edema: a chronically instrumented, awake sheep model mimicking human disease

Ethchlorvynol injection in humans leads to a clinical picture consistent with increased permeability pulmonary edema, ie, the adult respiratory distress syndrome. There has been only one such case reported in which the pulmonary wedge pressure was measured. In an attempt to mimic the human disease, the authors established the awake, unanesthetized chronic sheep lung lymph fistula model and injected 15 mg/kg of ethchlorvynol intravenously after a baseline period. There were transient increases in pulmonary artery and systemic blood pressure with decreases in cardiac output. Lymph flow increased five-fold and remained elevated for 24 hr, returning to normal by 48 hr. All animals survived. Pulmonary morphologic changes consisted of alveolar and interstitial edema and some disruption of endothelial and epithelial cells. These findings resolved by 48 hr postinjection. The authors conclude that this model mimics the findings in humans who have injected ethchlorvynol intravenously.     

A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with increased mortality in up to 10% of patients with rheumatoid arthritis. Lung exposure to cigarette smoke has been implicated in disease development. Little is known about the mechanisms underlying the development of RA-ILD, in part due to the lack of an appropriate mouse model. The objectives of this study were (i) to test the suitability of SKG mice as a model of cellular and fibrotic interstitial pneumonia in the setting of autoimmune arthritis, and (ii) to determine the role of lung injury in the development of arthritis in SKG mice. Lung tissues were evaluated in arthritic SKG mice by quantifying cell accumulation in bronchoalveolar lavage, static compliance, collagen levels, and infiltrating cell phenotypes by flow cytometry and histology. Lung injury was induced by exposure to cigarette smoke or bleomycin. Arthritic SKG mice developed a patchy cellular and fibrotic interstitial pneumonia associated with reduced static compliance, increased collagen levels, and accumulation of inflammatory cells. Infiltrating cells comprised CD4+ T cells, B cells, macrophages, and neutrophils. Chronic exposure to cigarette smoke or initiation of lung injury with bleomycin did not cause arthritis. The pattern of lung disease suggests that arthritic SKG mice represent an authentic model of nonspecific interstitial pneumonia in RA-ILD patients. The lack of arthritis development after cigarette smoke or lung injury suggests that a model where breaches in immunologic tolerance are induced by lung inflammation and injury alone may be overly simplistic.     

The effect of airway deposition on the assessment of lung injury by 99mTc-DTPA clearance--lung injury in interstitial lung diseases assessed by using the duplicated 99mTc-DTPA aerosol inhalation method

The 99mTc-DTPA aerosol inhalation method permits detection of pulmonary epithelial damage. We investigated one of several problems, airway deposition of inhaled aerosol, on the assessment of pulmonary epithelial permeability in healthy nonsmokers and patients with interstitial lung diseases. We used the rate constant of pulmonary 99mTc-DTPA clearance curve, k, as a parameter of the epithelial permeability. The alveolar-peripheral airway deposition of aerosol was estimated by the duplicated inhalation method, which we newly developed. The mean k in patients with interstitial lung diseases (2.52 +/- 0.72%/min, n = 8; p less than 0.01) was significantly greater than that in healthy nonsmokers (0.92 +/- 0.20%/min, n = 4). The alveolar-peripheral airway deposition was similar in both healthy nonsmokers and interstitial lung diseases (73.5 +/- 7.8% and 75.5 +/- 9.2%, respectively). The mean k corrected for alveolar-peripheral airway deposition (corrected k; kc) was higher in patients with interstitial lung diseases (4.08 +/- 1.63%/min; p less than 0.01) as compared with healthy nonsmokers (1.36 +/- 0.47%/min). The mean k was significantly greater than the mean kc in both groups (p less than 0.01, p less than 0.01). However, there was a significant correlation between the k and kc obtained among the subjects (r = 0.951; p less than 0.01). We, therefore, conclude that correction for alveolar-peripheral airway deposition was not necessary to distinguish the patients with interstitial lung diseases from the healthy nonsmokers using 99mTc-DTPA aerosol inhalation method although the correction was significant in the individual subjects.     

Cardiopulmonary changes occurring with pulmonary intravascular clearance of live bacteria in sheep

Sheep were infused with live bacteria to determine if the bacteria are phagocytized in the pulmonary circulation and to study the associated cardiopulmonary changes. Unanesthetized animals (n = 9) with chronic hemodynamic and pulmonary lymph catheters received a 1 hr central venous infusion of live Pseudomonas aeruginosa (5 x 10(7) Ps./minute) and were compared to a sham group (n = 7). The pulmonary arterial levels of bacteria were five to 100 times higher than the aortic levels. Pulmonary intravascular clearance rates were 79-91%. Electron microscopy of the lungs 24 hr after the bacterial infusion showed that pulmonary intravascular macrophages and neutrophils phagocytosed the bacteria. Severe initial and mild persistent pulmonary hypertension occurred. The pulmonary lymph flow was elevated, initially from hydrostatic pressure and later from increased permeability. A hyperdynamic circulation occurred from 6 to 18 hr, with elevated cardiac index and lowered systemic vascular resistance and mean arterial pressure, mimicking cardiopulmonary changes seen in clinical sepsis. The removal of bacteria in the lungs may contribute to the injury in sheep.