肺表面活性物质稀释剂延迟肺灌洗治疗烟雾吸入性损伤

目的 探讨外源性肺表面活性物质(PS)稀释剂延迟肺灌洗对大鼠严重烟雾吸入伤后内源性PS功能障碍和急性呼吸衰竭的治疗效果.方法 90只Wistar大鼠随机分为5组:Ⅰ组,正常对照(n=14);Ⅱ组,烟雾吸入(n=27);Ⅲ组,烟雾+PS灌洗+机械通气(MV),n=21;Ⅳ组,烟雾+盐水灌洗+MV,n=10;V组,烟雾+MV,n=18.伤后2 h经气管插管注入含PS(100ms/ks)的等渗盐水30 ml/kg或等量盐水行肺灌洗,MV 4 h,观察24 h;检测动脉血气、肺水量、静态肺顺应性(Cst)、支气管肺泡灌洗液(BAIF)蛋白含量、BALF表面张力特性和24 h病死率等.结果 致伤动物伤后立即出现严重缺氧和一氧化碳中毒;Ⅱ组发生急性呼吸衰竭、高通透性肺水肿和PS功能障碍;Ⅲ组Cst和BALF表面张力特性显著改善(P<0.05),但氧合能力、肺水量和BALF蛋白含量无明显好转(P>0.05).Ⅳ、V组疗效不佳.结论 外源性PS稀释剂延迟肺灌洗可一定程度恢复烟雾吸入所致内源性PS功能抑制,改善肺功能,但不能显著减轻高通透性肺水肿和呼吸衰竭,不能降低早期病死率.     

Toll-like receptor 4 deficiency causes pulmonary emphysema

TLRs have been studied extensively in the context of pathogen challenges, yet their role in the unchallenged lung is unknown. Given their direct interface with the external environment, TLRs in the lungs are prime candidates to respond to air constituents, namely particulates and oxygen. The mechanism whereby the lung maintains structural integrity in the face of constant ambient exposures is essential to our understanding of lung disease. Emphysema is characterized by gradual loss of lung elasticity and irreversible airspace enlargement, usually in the later decades of life and after years of insult, most commonly cigarette smoke. Here we show Tlr4(-/-) mice exhibited emphysema as they aged. Adoptive transfer experiments revealed that TLR4 expression in lung structural cells was required for maintaining normal lung architecture. TLR4 deficiency led to the upregulation of what we believe to be a novel NADPH oxidase (Nox), Nox3, in lungs and endothelial cells, resulting in increased oxidant generation and elastolytic activity. Treatment of Tlr4(-/- )mice or endothelial cells with chemical NADPH inhibitors or Nox3 siRNA reversed the observed phenotype. Our data identify a role for TLR4 in maintaining constitutive lung integrity by modulating oxidant generation and provide insights into the development of emphysema.     

糜蛋白酶在烟草烟雾诱导的仓鼠肺动脉高压中的作用

目的探讨糜蛋白酶在烟草烟雾所诱导的肺动脉重构和肺动脉高压中的作用。方法将仓鼠暴露在烟草产生的烟雾中（烟雾暴露组,n=6）,4个月后,使用免疫组织化学法、蛋白免疫印迹法、放射免疫学测定、反转录PCR等测定仓鼠肺的形态学和肺组织的生物化学改变。对烟雾暴露组与对照组（n=6）上述指标进行比较。结果长期烟草烟雾暴露使仓鼠右心室收缩压升高,肺小动脉中层细胞肥大,同时肺组织糜蛋白酶活性及合成增加,血管紧张素Ⅱ（AngⅡ）水平升高（与对照组比较,P均﹤0.05）。糜蛋白酶抑素（chymostatin）可以降低烟草诱导的仓鼠肺组织中糜蛋白酶活性的增加和AngⅡ水平,改善肺小动脉的重构程度,降低右心室收缩压,但对仓鼠肺组织中血管紧张素转换酶（ACE）的活性无影响。结论长期烟草烟雾暴露可增加仓鼠肺中糜蛋白酶的活性及表达,激活的糜蛋白酶进一步诱导肺组织AngⅡ形成,这可能是烟草诱导的肺动脉高压发生机制的一部分。因此,糜蛋白酶抑素也许会对吸烟的肺动脉高压患者有益。     

Inhaled tobacco sterols: uptake by the lungs and disposition to selected organs of rats

Tobacco sterols (cholesterol, beta-sitosterol, campesterol, and stigmasterol) are present in tobacco smoke and appear in plasma of mammals exposed to cigarette smoke. Because tobacco sterols may be important in the pathogenesis of smoking-induced lung and vascular diseases, we studied the pattern of deposition of cigarette sterols in the lungs and appearance of cigarette sterols in plasma and body organs of rats. After exposure to twenty 5 ml "puffs" of smoke from tobacco labeled with [4-14C]cholesterol or beta-[4-14C]sitosterol, rats were killed just after exposure (day 0) and on days 2, 5, 8, 11, 15, and 30, and the lungs and selected body organs analyzed for activity. We found that cigarette sterols are associated with particulates in cigarette smoke, deposited mostly in distal airspaces and parenchyma of the lungs, and appear in plasma and several body organs for more than 30 days after this single exposure to cigarette smoke. Bronchoalveolar lavage fluid contained relatively small amounts of radiolabel for only the first few days, suggesting that most of the sterols were rapidly incorporated in lung parenchyma. Because disorders of sterol metabolism have been implicated in a variety of diseases including atherosclerosis and cancer, the significance of tobacco sterols to human smoking-induced diseases deserves further study.     

Double impact of cigarette smoke and mechanical ventilation on the alveolar epithelial type II cell

Introduction

Ventilator-induced lung injury (VILI) impacts clinical outcomes in acute respiratory distress syndrome (ARDS), which is characterized by neutrophil-mediated inflammation and loss of alveolar barrier function. Recent epidemiological studies suggest that smoking may be a risk factor for the development of ARDS. Because alveolar type II cells are central to maintaining the alveolar epithelial barrier during oxidative stress, mediated in part by neutrophilic inflammation and mechanical ventilation, we hypothesized that exposure to cigarette smoke and mechanical strain have interactive effects leading to the activation of and damage to alveolar type II cells.

Methods

To determine if cigarette smoke increases susceptibility to VILI in vivo, a clinically relevant rat model was established. Rats were exposed to three research cigarettes per day for two weeks. After this period, some rats were mechanically ventilated for 4 hours. Bronchoalveolar lavage (BAL) and differential cell count was done and alveolar type II cells were isolated. Proteomic analysis was performed on the isolated alveolar type II cells to discover alterations in cellular pathways at the protein level that might contribute to injury. Effects on levels of proteins in pathways associated with innate immunity, oxidative stress and apoptosis were evaluated in alveolar type II cell lysates by enzyme-linked immunosorbent assay. Statistical comparisons were performed by t-tests, and the results were corrected for multiple comparisons using the false discovery rate.

Results

Tobacco smoke exposure increased airspace neutrophil influx in response to mechanical ventilation. The combined exposure to cigarette smoke and mechanical ventilation significantly increased BAL neutrophil count and protein content. Neutrophils were significantly higher after smoke exposure and ventilation than after ventilation alone. DNA fragments were significantly elevated in alveolar type II cells. Smoke exposure did not significantly alter other protein-level markers of cell activation, including Toll-like receptor 4; caspases 3, 8 and 9; and heat shock protein 70.

Conclusions

Cigarette smoke exposure may impact ventilator-associated alveolar epithelial injury by augmenting neutrophil influx. We found that cigarette smoke had less effect on other pathways previously associated with VILI, including innate immunity, oxidative stress and apoptosis.     

Effects of cigarette smoke on elastase secretion by murine macrophages.

Mice were chronically exposed to cigarette smoke for various time periods up to 4 weeks. As a consequence of the exposure, there was an increase in the number of alveolar macrophages obtained from the lungs of these mice. Light microscopic examination of cultured cells revealed increased numbers of highly pleomorphic cells filled with pigmented residues of cigarette smoke. These cells were more mitotically active, with a five fold increase in the number of alveolar colony-forming cells compared to the controls. When macrophages derived from mice exposed to cigarette smoke were cultured at high density in the absence of serum, they secreted significantly greater amounts of elastase than did the same number of control macrophages. At concentrations as low as 0.50 micrograms/ml, cycloheximide reversibly inhibited elastase secretion from both the control and experimental cultures. The effects of cigarette smoke inhalation on elastase secretion by alveolar macrophages do not appear to be a direct effect of cigarette smoke on these cells. Exposure of normal mouse macrophages in vitro to pulses of aqueous extracts of cigarette smoke, while significantly increasing secretion of elastase by peritoneal exudative macrophages, did not augment that of resident or exudative alveolar macrophages. These results suggest that the increased elastase secretion observed with the use of cultured macrophages derived from mice exposed to cigarette smoke is the result of either indirect activation of resident macrophages or the recruitment of a highly activated exudative population into the lungs of the exposed animals.     

Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice

Adipose tissue provides for a rich and easily accessible source of multipotent stromal cells and thus offers the potential for autologous cell-based therapy for a number of degenerative diseases. Senile osteoporosis is characterized by a reduction in bone quality, which is associated with inadequacies in bone marrow stromal cell (BMSC) differentiation. In the present study, we have characterized adipose-derived stromal cells (ASCs) isolated from aged osteoporotic mice and evaluated their suitability as a source of osteogenic precursor cells. Significant reductions in both tibia bone quality and telomere length in liver tissue were observed in the senescence-accelerated mouse prone 6 strain (SAMP6), as compared to the control age-matched senescence-accelerated mouse resistant 1 strain (SAMR1), thus confirming osteoporosis and accelerated ageing traits in this model. ASCs isolated from inguinal fat expressed mesenchymal surface markers and were capable of differentiating along the osteoblast, adipocyte and chondrocyte lineages. Telomere length was not compromised in ASCs from SAMP6 mice but was actually found to be significantly increased as compared to control SAMR1 mice. Furthermore, ASCs from both strains were comparable in terms of telomerase activity, p21 mRNA expression, SA-β-gal activity and proliferative capacity. The overall osteogenic and adipogenic potential of ASCs was comparable between SAMP6 and SAMR1 strains, as determined by quantitative molecular, biochemical and histological analyses. In conclusion, adipose tissue may represent a promising autologous cell source for the development of novel bone regenerative therapeutic strategies in the treatment of age-related osteoporosis.     

Effects of an L-selectin antibody on the pulmonary and systemic manifestations of severe smoke inhalation injuries in sheep

Sheep were treated with either lymphocyte adhesion molecule (LAM)1-3, an antibody against L-selectin, (40 mg 1 hour before smoke inhalation and 35 mg 24 hours after smoke inhalation; n = 6) or equivalent volumes of 0.9% saline solution (n = 6). After the smoke inhalation injuries, the PaO2/FIO2 ratio declined in both groups until 40 hours after the injuries, when a trend toward improvement was noted in the group that received LAM1-3. Lung lymph flow increased in both groups until 36 hours after the smoke inhalation injuries and then significantly decreased in the group that received LAM1-3. Forty-eight hours after the smoke inhalation injuries, there was a significant decrease in the ratio of wet-dry lung weight and in preservation of the reflection coefficient in the group that received LAM1-3 (P < .05). Histopathologic examination showed no differences between the groups in the pulmonary morphology associated with smoke inhalation. A reduction in splanchnic blood flow was noted in the control group (P < .05); this reduction was attenuated by treatment with LAM1-3. The delayed pulmonary effects and improved splanchnic blood flow suggested that LAM1-3 attenuated the development of a systemically induced secondary lung injury rather than of the primary lung injury associated with smoke inhalation.     

The effect of dopamine on pulmonary hemodynamics and tissue damage after inhalation injury in an ovine model.

Hypoxic pulmonary vasoconstriction and reduced blood flow occur as a result of smoke inhalation. The aim of this study was to investigate how the amelioration of blood flow reduction by the vasodilator dopamine affects histopathologic outcome. We exposed the left lungs of chronically instrumented sheep (n = 12) to smoke, awakened them, and studied them for 24 hours. Six hours after inhalation injury, the sheep received randomized infusions of dopamine (9 micrograms/kg/min) or equal volumes of 0.9% saline solution. Pulmonary resistance in the left lungs of animals in the group that received saline solution rose continuously throughout the study period (624 +/- 48 dyne.sec.cm-5/m2 to 1747 +/- 140 dyne.sec.cm-5/m2, baseline to 24 hours after injury). Dopamine treatment caused a significantly lower vascular resistance in the injured lung than did saline solution between 8 and 24 hours after injury. The histologic evaluation of the injured lungs showed epithelial necrosis and cast formation in both groups in addition to an increased wet/dry ratio. No difference in lung injury between the groups could be distinguished. We conclude that the amelioration of blood flow reduction by treatment with dopamine in the lungs that were exposed to smoke did not affect pulmonary damage after inhalation injury.     

一氧化氮对吸入性损伤犬肺功能的改善作用及机制

目的：评价吸入一氧化氮（ＮＯ）对烟雾吸入性损伤犬肺功能的改善效果，并验证其作用机制。方法：２１只犬随机分为３组，烟雾吸入后的对照组（８只）给予单纯吸氧（ＦｉＯ２０．４５）；治疗组（９只）吸氧（ＦｉＯ２０．４５）＋０．００４５％ＮＯ，连续监测１２小时血气变化；正常组（４只）不致伤，用于建立组织学对照。数据行多个样本均数间方差分析。结果：治疗组肺氧合功能明显改善（Ｐ均＜０．０５），肺通气功能也明显改善（Ｐ均＜０．０５）；动脉血和肺组织环磷酸鸟苷（ｃＧＭＰ）明显升高（Ｐ均＜０．０１）。结论：吸入ＮＯ能明显改善肺功能，其作用机制为提高平滑肌细胞内ｃＧＭＰ水平。推荐临床应用吸入ＮＯ作为吸入性损伤的综合治疗方法。     

烟雾吸入致伤犬右侧肺引发左侧肺损伤的实验研究

目的：探讨烟雾致伤犬一侧肺对另侧肺的影响及其机制。方法：在Olympus(型号P10）纤维支气管镜引导下直视行双腔管气道插管,烟雾吸入致伤犬右侧肺,分别采用AVL990型自动血气分析仪、干湿重法、过氧化氢还原法、微量酸滴定法、TBA法、生物测定法检测犬动脉血气、肺含水量、髓过氧化物酶（MPO）活性、磷脂酶A2（PLA2）活性、脂质过氧化物丙二醛（MDA）及血小板活化因子（PAF）含量。结果：右侧肺烟雾吸入致伤后,犬呼吸频率明显增快,动脉血氧分压（PaO2)进行性下降,24小时达8．37kPa(1kPa=7.5mmHg)。但动脉血二氧化碳分压（PaCO2)仅24小时点与伤前比较显著升高。进一步研究发现,烟雾致伤后右侧肺后24小时,左侧肺含水量明显增加,粒细胞标志酶MPO活性、膜磷脂分解酶PLA2活性、炎性介质PAF及MDA含量与正常对照组比较均显著升高。病理检查见,致伤犬双肺弥漫性肺泡内水肿,间隔增厚,伴大量炎细胞浸润,惟左侧肺略轻。结论：烟雾吸入致伤犬一侧肺可引起另侧肺水肿,其机制与另侧肺组织继发性的白细胞浸润、PLA2活化、脂质过氧化损伤及炎性介质PAF增加有关。     

骨髓间充质干细胞移植对烟雾吸入性损伤兔早期肺组织的影响

目的 探讨骨髓间充质干细胞(MSCs)移植对烟雾吸入性损伤兔早期肺组织损伤的影响.方法 采用直接贴壁法体外培养兔MSCs,用流式细胞术鉴定MSCs.将48只兔制备烟雾吸入性损伤模型后按随机数字表法均分成致伤组和MSCs组.MSCs组伤后立即静脉给予含1×107个/ml MSCs的磷酸盐缓冲液(PBS)10 ml;致伤组则给予10 ml PBS.分别于干预后2、6和24 h活杀8只兔,取肺组织行组织病理学观察,同时进行肺损伤评分.结果 流式细胞术检测显示所培养细胞为MSCs.肺大体标本和光镜下均观察到MSCs组肺损伤程度较致伤组明显减轻.虽然MSCs组和致伤组伤后2 h肺损伤评分(分)比较差异无统计学意义(4.0±0.7比4.5±0.6,P＞0.05),但MSCs组伤后6 h和24 h肺损伤评分(分)明显低于致伤组(6 h:6.1±0.9比8.2±0.9,24 h:4.6±0.9比10.4±0.8,均P＜0.01).结论 MSCs移植能明显减轻烟雾吸入性损伤兔肺组织损伤,改善肺损伤评分.

Abstract：

Objective To explore the effect of bone marrow mesenchymal stem cells (MSCs)engraftment on lung tissue at early stage of smoke inhalation injury in rabbits. Methods MSCs were proliferated by the method of whole marrow culture and identified by flow cytometry. Forty-eight rabbits were randomly divided into smoke inhalation group (S group) and MSCs group (M group) after reproduction of rabbit smoke inhalation injury model. 10 ml of phosphate buffer saline (PBS) containing 1 × 107/ml MSCs was intravenously injected in M group, meanwhile 10 ml PBS was injected intravenously in S group. Eight rabbits were sacrificed at 2, 6 and 24 hours after intervention, and the lung tissue was harvested for morphological and pathological observation, and lung injury score was used to evaluate smoke inhalation injury.Results Cultured cells were confirmed to be MSCs with flow cytometry. Lung injury in rabbits of M group was less serious in morphology and histopathology than that in S group. Though there was no significance in lung injury score between M group and S group at 2 hours after injury (4.0±0.7 vs. 4.5±0.6, P＞0.05),the lung injury scores in M group at 6 hours and 24 hours after injury were significantly lower than those in S group (6 hours: 6.1±0.9 vs. 8.2±0.9, 24 hours: 4. 6±0.9 vs. 10.4±0. 8, both P＜0. 01). Conclusion Intravenous engraftment of MSCs could ameliorate lung injury induced by smoke inhalation, and improve lung injury score significantly.     

Elastin fragments drive disease progression in a murine model of emphysema

Mice lacking macrophage elastase (matrix metalloproteinase-12, or MMP-12) were previously shown to be protected from the development of cigarette smoke-induced emphysema and from the accumulation of lung macrophages normally induced by chronic exposure to cigarette smoke. To determine the basis for macrophage accumulation in experimental emphysema, we now show that bronchoalveolar lavage fluid from WT smoke-exposed animals contained chemotactic activity for monocytes in vitro that was absent in lavage fluid from macrophage elastase-deficient mice. Fractionation of the bronchoalveolar lavage fluid demonstrated the presence of elastin fragments only in the fractions containing chemotactic activity. An mAb against elastin fragments eliminated both the in vitro chemotactic activity and cigarette smoke-induced monocyte recruitment to the lung in vivo. Porcine pancreatic elastase was used to recruit monocytes to the lung and to generate emphysema. Elastin fragment antagonism in this model abrogated both macrophage accumulation and airspace enlargement.     

Continuous nebulized albuterol attenuates acute lung injury in an ovine model of combined burn and smoke inhalation

OBJECTIVE: Albuterol, due to its bronchodilatory and anti-inflammatory effects, is given via continuous nebulization in children with severe asthma. Combined burn and smoke inhalation injury frequently results in acute lung injury due to a combination of airway obstruction and inflammation. We hypothesized that albuterol administered via continuous nebulization would mitigate acute lung injury after smoke inhalation injury and burn. DESIGN: Randomized prospective animal model. SUBJECTS: Twenty adult female sheep (mean weight, 33.1+/-0.9 kg). INTERVENTIONS: Adult ewes were subjected to a 40% body surface area third-degree flame burn and smoke inhalation injury after tracheostomy. Sheep were allocated to a) sham group, b) saline continuous nebulization group, c) 20 mg of albuterol continuous nebulization group, or d) 40 mg of albuterol continuous nebulization group (n=5 animals per group). All groups received intravenous lactated Ringer's solution at 4 mL.kg-1.%burn(-1).24 hrs-1 for resuscitation and were equally mechanically ventilated throughout the 48-hr study period. Pulmonary and cardiac function, lung lymph flow, bronchial obstruction score, and wet/dry lung weights were recorded. RESULTS: Compared with saline and control groups, the albuterol groups had lower pause and peak inspiratory pressures, decreased pulmonary transvascular fluid flux, a significantly higher Pao2/Fio2 ratio, and decreased shunt fraction at 48 hrs postinjury. The wet-to-dry lung weight ratio and bronchial obstruction scores were lower for sheep receiving albuterol. CONCLUSIONS: Continuous nebulization of albuterol improves pulmonary function via improved airway clearance and decreased fluid flux in a combined burn/smoke inhalation injury model.     

Lack of hematogenous mediated pulmonary injury with smoke inhalation

Inhalation injury was studied in chronically prepared sheep (n = 12) by insufflating one lung with cotton smoke from burning cotton cloth. The contralateral lung was insufflated with air. There was also a sham group in which both lungs were insufflated with air (n = 6). The pulmonary status of the smoked animals gradually deteriorated; by 24 hours shunt blood flow had increased to 32 +/- 3% and the animals were sacrificed. Wet-weight/dry-weight ratios were elevated only in the smoke-exposed lungs. They likewise showed histologic evidence of injury. Lavage materials from the injured lungs had higher percentages of neutrophils than the others. The lung lesion produced by the inhalation of cotton smoke appears to be localized to the area of injury, rather than being a generalized pulmonary response.     

A novel animal model of sepsis after acute lung injury in sheep

OBJECTIVE: Patients with acute lung injury after smoke inhalation often develop pneumonia subsequently complicated by sepsis. This often is a fatal complication. The aim of this study was to develop a standardized and reproducible model of hyperdynamic sepsis after smoke inhalation in sheep. DESIGN: Prospective, experimental study in sheep. SETTINGS: Experimental laboratory in a university hospital. SUBJECTS: Twenty-one female Merino ewes. INTERVENTION: Animals were anesthetized and surgically prepared for this chronic study. After a week of recovery, baseline data were collected. After tracheostomy was performed, sheep were connected to a volume-controlled ventilator. Acute lung injury was produced by insufflating the lungs with 48 breaths of cotton smoke. During halothane anesthesia, live bacteria suspended in a 30-mL saline solution containing 2-5 x 10(11) colony-forming units were instilled through a bronchoscope into the right lower and middle lung lobes (10 mL each) and left lower lung lobe (10 mL; n = 10). Eleven sheep were given smoke but not bacteria. After injury and the bacterial challenge, the animals were ventilated mechanically with 100% oxygen. The animals were monitored for 48 hrs. was detected in blood cultures after 14-48 hrs. MEASUREMENTS AND MAIN RESULTS: The sheep developed a hyperkinetic cardiovascular response concomitant with a decrease in Pao similar to severe sepsis in human patients who meet the criteria for acute respiratory distress syndrome (PaO2 /FIO2 <200). These changes were more severe than in animals exposed to smoke inhalation alone. Mean arterial pressures at 48 hrs in the smoke-alone and the smoke + sepsis group were 85.5 +/- 5.2 and 68.1 +/- 7.6 mm Hg, respectively (mean +/- se, p<.05). CONCLUSION: This animal model closely resembles hyperdynamic sepsis in humans and may be of great value for studies of sepsis with smoke inhalation.     

Early effects of inhalation injury on lung mechanics and pulmonary perfusion

We investigated the early effects of a rather large amount of cotton-smoke on lung mechanics and pulmonary perfusion. Under halothane anesthesia 18 ewes were intubated with a double-lumen tube. In 6 sheep the left lung was exposed to smoke, in another 6 the right lung. A sham group of 6 sheep was insufflated with air instead of smoke. Prior to and 30–45 min following the smoking- (sham-) procedure the following parameters were determined for the smoke- (sham-) exposed and the contralateral lung: static compliance, inspiratory airway resistance, and physiologic dead space ratio. In addition MAP, MPAP, WP, and CO were recorded. The data indicate that inhalation of large amounts of smoke has no major direct effects on pulmonary mechanics and perfusion in the early post-injury period. Only an increase in airway resistance of the smoke exposed lungs was found, which must be attributed to a local reflex mechanism. Presented in part at the Society of Critical Care Medicine 15th Annual Educational and Scientific Symposium, Washington, DC, USA, 27–31 May 1986     

Inhaled cigarette smoke selectively reverses human hypoxic vasoconstriction

The acute effects of the inhaled gas phase of cigarette smoke on pulmonary (PAP) and systemic (SAP) arterial pressures and on plasma arterial cGMP content were compared with those of inhaling 10, 20 and 80 ppm nitric oxide (NO) in one healthy adult volunteer spontaneously breathing a hypoxic gas mixture. Hypoxia (FIO₂ 0.12) induced a sustained, stable pulmonary vasoconstriction. Inhaled NO induced a dose-dependent fall in PAP; plasma cGMP rose from 39.4 (hypoxia) to 164 pmol/ml (hypoxia plus 80 ppm NO). Exposure to cigarette smoke induced a rapid, consistent and reversible fall in PAP; plasma cGMP rose from 45.5 (hypoxia) to 138 pmol/ml (hypoxia plus cigarette smoke). Neither NO nor cigarette smoke inhalation induced any change in SAP. These data suggest that exposure to cigarette smoke is able selectively to reverse acute hypoxic vasoconstriction in humans without causing systemic vasodilation, an effect likely mediated through the NO-cGMP pathway.     

Trauma: the acute response

Moderate to severe trauma is followed by a local response, which involves changes in cell function and an inflammatory reaction, and a systemic response coordinated by the nervous and endocrine systems. Early post-trauma alterations in cells are due primarily to decreased oxygen supply and include 1) the shifting of electrolytes and water, either into or out of cells, and 2) the production or release of various local tissue factors. These tissue factors produce changes in blood flow, increased vascular permeability, and other local manifestations of inflammation. Trauma activates nervous and hormonal pathways which help to restore blood volume and maintain the function of essential organs. The effects of these responses on cellular oxygen consumption and body temperature are described. Examples of respiratory system involvement in response to trauma in the lungs or elsewhere are given. These include increased capillary permeability in the lungs, pulmonary emboli, and damage from smoke and heat inhalation.