猪同种异体原位左肺移植模型的建立

目的建立接近于人的猪同种异体左肺原位移植动物模型。方法环江香猪12只作为供体,巴马香猪12只作为受体,左侧第4肋间开胸,完成左肺原位移植。术后1、2、4、6、12 h开胸测左、右肺动脉的压力,同时取左、右肺静脉血进行血气分析,取左、右肺组织,观察含水量及病理学改变。结果动物术后均存活,随着术后时间延长,供肺静脉血氧合指数(Pa O2/Fi O2)下降和肺动脉压(PAP)上升,与受体正常肺比较,差异有显著性(P0.05)。随着时间的推移,移植肺组织出现水肿、炎性细胞浸润、红细胞渗出,肺泡壁增厚明显,部分肺泡腔完全闭塞,部分肺组织实变等变化,与受体肺组织比较,含水量增加显著(P0.05)。结论为研究肺移植缺血再灌注损伤及免疫排斥反应研究机制提供了理想的动物模型。     

银杏提取物对大鼠肺缺血/再灌注损伤的保护作用

目的：观察银杏提取物（EGB）对大鼠体外循环肺缺血／再灌注损伤（I／R）的保护作用。方法：建立离体大鼠肺灌流模型．SD大鼠随机分成假手术组（Sham）、I／R组和EGB组,观察大鼠肺组织形态学改变、分别测定肺组织匀浆及灌流液中超氧化物歧化醇（SOD）、丙二醛（MDA）的含量、肺湿干重比（W／D）和平均肺动脉压（MPAP）。结果：HE染色显示EGB组肺损伤明显减轻、肺组织湿／干重比和MPAP显著低于I／R组：EGB组肺脏灌流液和组织匀浆中SOD的活性显著高于I／R组,MDA含量则显著低于I／R组。结论：EGB对大鼠肺I／R损伤具有保护作用。     

持续灌注和静态保存对中性粒细胞凋亡的影响

为研究体外循环机持续灌注、间断压力灌注、单纯低温保存犬离体肺对支气管肺泡灌洗液中中性粒细胞凋亡变化以及对肺泡巨噬细胞吞噬凋亡中性粒细胞的影响,探索最佳的离体肺保存方式,将30只Mongrel犬随机分成3组,为体外循环组、压力灌注组和低温保存组,每组10只。在保持机械通气的条件下,完整摘取双肺,3种不同方式保存离体肺,并按时间点留取支气管肺泡灌洗液标本。流式细胞仪检测犬离体肺支气管肺泡灌洗液中中性粒细胞凋亡,免疫组织化学法检测犬离体肺肺泡巨噬细胞对凋亡中性粒细胞吞噬。随着犬肺离体时间的推移,各实验组离体肺支气管肺泡灌洗液中凋亡的中性粒细胞明显减少,在每个时间点上,体外循环组中性粒细胞的凋亡最多,压力灌注组中次之,低温保存组中最少。各实验组吞噬凋亡中性粒细胞的巨噬细胞随着离体时间的延长呈逐渐减少的趋势,在肺离体各时间点上,体外循环组中巨噬细胞对凋亡中性粒细胞的吞噬清除优于间断压力灌注组和单纯低温保存组。采用体外循环机持续灌注犬离体肺,能增加中性粒细胞凋亡,促使吞噬细胞吞噬凋亡的中性粒细胞,避免发生凋亡延迟,从而减轻离体肺组织的缺血再灌注损伤,具有较好的肺保护作用。     

三种犬离体肺保存方式对肺表面活性物质的影响

为研究3种不同的犬离体肺保存方式对支气管肺泡灌洗液中肺表面活性物质的影响。随机将30只Mongrel犬分成3组,为体外循环灌注组、间断压力灌注组和单纯低温保存组,每组10只。在保持机械通气的条件下,摘取犬双肺,3种不同方式保存离体肺,按时间点留取支气管肺泡灌洗液标本,BCA法测定总蛋白浓度,抗坏血酸法测定总磷脂的含量,薄层色谱分析测定二棕榈酸磷脂酰胆碱含量,酶联免疫吸附试验检测白介素(IL-1a/2/6/8)。随着犬肺离体时间的推移,各实验组离体肺支气管肺泡灌洗液中DPPC/PL的比值呈时间依赖性下降,各白介素/总蛋白比值呈时间依赖性升高。在同一时间点上,体外循环灌注组中DPPC/PL的比值最高,间断压力灌注组次之,单纯低温保存组最低;体外循环灌注组中各白介素/总蛋白的比值最低,间断压力灌注组次之,单纯低温保存组最高。采用体外循环机持续灌注犬离体肺,离体肺中可维持较高浓度的肺泡表面活性物质,维持肺泡表面张力,发挥肺保护作用,这可能与抑制炎症介质的释放有关。     

滚压泵在乳猪肺灌注模型建立中的应用

目的通过滚压泵建立一种操作简单的猪隔离肺持续灌注和缺血再灌注模型,并比较两种灌注方法对肺的损伤。方法12只乳猪随机分为缺血再灌注组（对照组）和持续灌注组（实验组）。分别在左、右心耳以及肺动脉插管。滚压泵将贮血器中的灌注液泵入肺动脉,灌注双肺后再通过左心耳将灌注液引流回贮血器,建立猪肺灌注模型。对照组双肺停止灌注90min后灌注30min,实验组双肺持续灌注120min,灌注流量均为80mL/kg.min。测定实验前后的肺静态顺应性以及灌注液中TNF-α、IL-6变化。测定肺组织湿干比并进行电镜观察。结果实验组肺静态顺应性（实验组6.14±1.17mL/cmH2O,对照组7.89±0.94mL/cmH2O,p=0.017）、湿干比（对照组5.18±0.97,实验组3.84±1.08,P=0.048）、TNF-α指标均优于对照组（实验组0.80±0.26ng/mL,对照组0.52±0.15ng/mL,P=0.044）（P〈0.05）,电镜下的肺损伤程度轻于对照组。结论通过滚压泵建立猪肺持续灌注和缺血再灌注模型具有操作简便的特点。持续性非搏动灌注较之缺血再灌注对肺的损伤更轻。     

Kyoto-1保存液保存的移植用肺Ⅱ型肺泡上皮细胞钠-钾泵的研究

目的：临床认为肺水肿已成肺移植过程中的最大障碍。近年来资料表明,过是肺泡液的吸收与Ⅱ型肺泡上皮细胞Na^ 的跨膜能力有关,保存中若能保持肺上Na^ -K^ -ATPase的活性,对成功的肺移植是非常必要的,本实验研究0℃、4℃Kyoto-1（NewET－K）保存液保存体肺脏,型Ⅱ肺泡上皮细胞Na^ -K^ -ATPase的活性变化,为Kyoto-1在临床上最大时限地保存供体肺提供基础理论依据。方法：取Wistar大白鼠,随机分为对照组和实验组,对照组取新鲜肺脏。实验组分别灌注0℃、4℃的Kyoto-1保存液,分别放入0℃、4℃冰箱中保存4h,24h,48h,进行光,电镜酶组织化学研究。使用图像分析系统进行定量测定。结果：4℃、24h实验组钠泵活性可以得到较好的保存（P＞0．05）。结论：钠泵可以作为检测供保存质量的重要指标。     

慢性低氧性肺动脉高压大鼠肺组织内质网应激介导的凋亡的变化

目的:探讨内质网应激介导的凋亡在低氧性肺动脉高压大鼠肺组织中的变化及意义.方法:清洁级雄性SD大鼠22只随机被均分成对照组和低氧组(n=11).采用常压低氧法复制慢性低氧高二氧化碳性肺动脉高压模型,4周后,测定肺动脉平均压(mPAP)、右心室游离壁(RV)和左心室加室间隔(LV+S)重量比、肺细小动脉管壁面积/管总面积...     

急性缺氧动物吸入纯氧后再缺氧损伤机理的研究

目的:观察急性缺氧动物再缺氧损伤现象及探讨其发生机理.方法:采用右心漂浮导管检测法,及放免法测定了血浆ET1含量的变化.结果:急性缺氧动物肺动脉平均压在吸入100%氧气后即明显下降,在突然停止吸氧而改吸室内空气后,下降的肺动脉压逐渐回升,5 min后恢复到吸氧前水平,但随着时间的延长,肺动脉压继续攀升,10 min后肺动脉压已明显高于吸氧前水平,15min后,肺动脉压达最高值,与此同时,缺氧动物心率、肺血管阻力、血浆ET1水平均显著高于吸氧前水平,而血氧分压反较吸氧前低.结论:急性缺氧动物存在着再缺氧损伤,而血浆ET1升高引起的肺动脉压异常升高在其发生中起重要作用.     

老年人，请保护好你的肺

我们知道,肺脏的主要功能是吸进空气中的氧气,排出人体代谢产生的废气——二氧化碳,俗称。吐故纳新”。若是肺脏不能吸进足够的氧气,排不出二氧化碳,血液里的氧气就会减低,二氧化碳就会增高,人就会感到气短,导致呼吸急促,严重时会出现口唇、指甲发绀,医学上称作呼吸功能不全。     

老年人，请保护好你的肺

我们知道,肺脏的主要功能是吸进空气中的氧气,排出人体代谢产生的废气——二氧化碳,俗称。吐故纳新”。若是肺脏不能吸进足够的氧气,排不出二氧化碳,血液里的氧气就会减低,二氧化碳就会增高,人就会感到气短,导致呼吸急促,严重时会出现口唇、指甲发绀,医学上称作呼吸功能不全。     

Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and “pearls of wisdom”/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible.     

Ascorbic acid prolongs the viability and stability of isolated perfused lungs: A mechanistic study using 31P and hyperpolarized 13C nuclear magnetic resonance

Ex vivo lung perfusion (EVLP) has recently shown promise as a means of more accurately gauging the health of lung grafts and improving graft performance post-transplant. However, reperfusion of ischemic lung promotes the depletion of high-energy compounds and a progressive loss of normal mitochondrial function, and it remains unclear how and to what extent the EVLP approach contributes to this metabolic decline. Although ascorbate has been used to mitigate the effects of ischemia–reperfusion injury, the nature of its effects during EVLP are also not clear. To address these uncertainties, this study monitored the energy status of lungs during EVLP and after the administration of ascorbate using ³¹P and hyperpolarized ¹³C NMR (nuclear magnetic resonance). Our experiments demonstrated that the oxidative phosphorylation capacity and pyruvate dehydrogenase flux of lungs decline during ex vivo perfusion. The addition of ascorbate to the perfusate prolonged lung viability by 80% and increased the hyperpolarized ¹³C bicarbonate signal by a factor of 2.7. The effect of ascorbate is apparently due not to its antioxidant quality but rather to its ability to energize cellular respiration given that it increased the lung’s energy charge significantly, whereas other antioxidants (glutathione and α-lipoic acid) did not alter energy metabolism. During ascorbate administration, inhibition of mitochondrial complex I with rotenone depressed energy charge and shifted the metabolic state of the lung toward glycolysis; reenergizing the electron transport chain with TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) recovered metabolic activity. This indicates that ascorbate slows the decline of the ex vivo perfused lung’s mitochondrial activity through an independent interaction with the electron transport chain complexes.     

Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death

Background

Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs.

Methods

C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs.

Results

Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix.

Conclusions

These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of donor lungs. The therapeutic benefits of EVs are in part mediated through anti-inflammatory promoting mechanisms via attenuation of immune cell activation as well as prevention of endothelial barrier integrity to prevent lung edema. Therefore, MSC-derived EVs offer a potential therapeutic strategy to treat post-transplant IR injury as well as rehabilitation of DCD lungs.

     

The extracorporeal perfusion of swine uterus as an experimental model: the effect of oxytocic drugs.

The objective of this study was to establish an experimental model for extracorporeal perfusion of swine uterus. In order to validate this model, we examined some biochemical parameters and determined the effect of oxytocic drugs (Oxytoxin, Prostaglandin E (2)) on extracorporeal perfused swine uteri. Thirty swine uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer for a period up to eleven hours with the aim to preserve a viable organ, which should be responsive to hormones. The intrauterine pressure was recorded after administration of various concentrations of oxytocin and prostaglandin E (2). Perfusate pH, perfusate lactate, partial oxygen and carbon dioxide tensions, oxygen saturation, and hydrogencarbonate levels in the perfusate, all indicators of tissue ischemia or cell necrosis, showed good preservation of the organ for up to seven hours. We examined the relation of intrauterine pressure to oxytocin and prostaglandin E (2). Both were able to induce contractions of the uterus, whereas prostaglandin E (2) produced rhythmical contractions of smaller amplitude and a higher frequency. We could demonstrate that our perfusion system was able to preserve the swine uterus in a functional condition appropriate for the study of physiological questions.     

Spontaneous injury in isolated sheep lungs: role of resident polymorphonuclear leukocytes.

Perfusion of isolated sheep lungs with homologous blood caused pulmonary hypertension and edema that was not altered by depletion of perfusate polymorphonuclear (PMN) leukocytes (D. B. Pearse et al., J. Appl. Physiol. 66: 1287-1296, 1989). The purpose of this study was to evaluate the role of resident PMN leukocytes in this injury. First, we quantified the content and activation of lung PMN leukocytes before and during perfusion of eight isolated sheep lungs with a constant flow (100 ml.kg-1.min-1) of homologous blood. From measurements of myeloperoxidase (MPO) activity, we estimated that the lungs contained 1.2 x 10(10) PMN leukocytes, which explained why the lung PMN leukocyte content, measured by MPO activity and histological techniques, did not increase significantly with perfusion, despite complete sequestration of 2.0 x 10(9) PMN leukocytes from the perfusate. MPO activities in perfusate and lymph supernatants did not increase during perfusion, suggesting that lung PMN leukocytes were not activated. Second, we perfused lungs from 6 mechlorethamine-treated and 6 hydroxyurea-treated sheep with homologous leukopenic blood and compared them with 11 normal lungs perfused similarly. Despite marked reductions in lung PMN leukocyte concentration, there were no differences in pulmonary arterial pressure, lymph flow, or reservoir weight between groups. Extravascular lung water was greater in both groups of leukopenic lungs. These results suggest that resident PMN leukocytes did not contribute to lung injury in this model.     

N-oxidation of imipramine by isolated perfused rat and rabbit lung

Pulmonary uptake and metabolism of imipramine (IMP) was investigated in isolated perfused rat (IPrL) and rabbit (IPRL) lung preparations. Perfusate containing ¹⁴C-IMP (1.2 μmole/g lung) was recirculated through the pulmonary artery in artificially ventilated lungs. The radioactivity in the perfusate declined rapidly and about 80% of the dose was taken up by the lungs within 10 minutes in both IPrL and IPRL preparations. A steady-state was apparently reached thereafter in the IPRL, while a portion of the radiolabel effluxed into the perfusate of the IPrLs, thus reducing the net lung content to 54% of added IMP by 60 minutes. After 60 minutes perfusion, metabolites of IMP accounted for the major radioactivity (80%) in the perfusate, while the lung contained mainly (83%) the unchanged parent compound. The principal metabolite was identified as IMP-N-oxide (IMP-NO) which was found in the perfusate after 5 minutes of perfusion. Only 3% of the added IMP was metabolized by IPRL in 60 minutes. SKF-525A, an inhibitor of cytochrome P-450-mediated monooxygenase system, did not inhibit but enhanced the metabolism of IMP by IPrL to IMP-NO. IMP was principally metabolized to IMP-NO by incubations of 9,000 g supernatant fractions of rat lungs to a significantly higher extent than similar rabbit lung preparations. Including SKF-525A significantly accelerated the metabolism of IMP to IMP-NO in accordance with the perfusion experiments. These results suggest that in contradiction to publishedd reports, IMP is appreciably metabolized by the rat lung $\text{via}$ N-oxidation by non-cytochrome P-450 pathway and the metabolite formed in the lung is released into the circulation indicating its low affinity for the lung tissue.     

Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.     

Actions of lipoxygenase metabolites in isolated rat lungs

Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. We examined the production and action of lipoxygenase metabolites in isolated lungs, where we controlled the perfusing fluid used. Arachidonate injected into isolated rat lungs perfused with cell- and protein-free physiological salt solution caused a transient pressor response. Following indomethacin, arachidonate caused a delayed slow pressure rise followed by edema. The lung effluent contracted the guinea pig ileum. High-pressure liquid chromatography (HPLC) analysis of the perfusate demonstrated the presence of leukotrienes (LTC4 and LTD4). Diethylcarbamazine, a leukotriene synthesis inhibitor, prevented the slow pressure rise and edema seen after indomethacin plus arachidonate. In lungs perfused with cell- and protein-free physiological salt solution, LTC4, but not LTD4, caused a transient pressure rise followed by a sustained pressure rise. The sustained rise was abolished by a leukotriene-receptor blocker (FPL 55712) but not by indomethacin. In blood-perfused lungs, LTC4 caused only the transient pressure rise that was not blocked by FPL 55712. In lungs perfused with physiological salt solution containing albumin, LTC4 had no effect. We concluded that 1) perfused nonsensitized rat lungs produced LTC4 and LTD4; 2) LTC4 may be a major pulmonary vasoconstrictor; and 3) albumin binding limits the pressor effect of LTC4.     

Protective effect of alpha-human atrial natriuretic polypeptide (alpha-hANP) on chemical-induced pulmonary edema

It has been established that alpha-hANP, the newly discovered peptide extracted from human cardiac atria, has potent natriuretic and hypotensive actions. Our present investigation is the first to demonstrate that alpha-hANP is capable of protecting against pulmonary edema caused by various chemicals, using isolated perfused guinea pig lung system. Lungs were perfused via pulmonary artery with Krebs-Ringer bicarbonate buffer at 5.0 ml/min, and wet weight of lungs and perfusion pressure of pulmonary artery (Pa) were monitored. Bolus injection of Triton-X or CHAPS into cannulated pulmonary artery produced edema as indicated by a massive increase in wet weight and a slight increase in Pa. Constant infusion of alpha-hANP through pulmonary artery at 200 ng/ml was effective in causing decrease in wet weight of lung. Perfusion of lung with paraquat or PGF2 alpha, and repeated bolus injection of arachidonic acid or PGE2 caused elevation in both wet weight of lung and Pa. The treatment with alpha-hANP similar to that described above also protected against edema caused by paraquat or arachidonic acid. Bolus administration of epinephrine induced a slight increase in wet weight and Pa, and alpha-hANP was effective in decreasing the elevated lung wet weight and Pa of lungs. Infusion or bolus administration of alpha-hANP into control lungs increased cGMP level in outflow perfusate as well as in lung tissue significantly. In lungs with edema which were induced by Triton-X or paraquat, there was a slight increase in cGMP level in Triton-X treated and no increase in paraquat treated lung tissues. In either cases, was there any increase in cGMP level in perfusate. The specific binding study of [125I]alpha-hANP revealed that the lack of increase in cGMP was not due to a loss of receptor in Triton-X or paraquat treated lungs. Thus our study demonstrated that alpha-hANP had a direct anti-edematic action(s) in lung which was not secondary to the systemic natriuretic and/or hypotensive action(s).     

The metabolism of 3-H-cortisone and 3-H-cortisol by the isolated perfused rat and guinea pig lungs.

Isolated perfused rat lungs removed more than 35% of 3-H-cortisone (1 times 10-9M) from the perfusate during one passage through the pulmonary circulation. The cortisone in the lungs was then rapidly converted to cortisol, which was returned to the perfusate. The tritiated steroid taken up was so rapidly washed from the lung, that only 10% remained after a 12 minute perfusion with steroid-free medium. In recirculating experiments, nearly 60% conversion to cortisol occurred over 32 cycles; in addition, there was a slow increase in the percentage of polar compounds in the medium. Similarly, the perfused hindlimbs preparation from the rat converted cortisone to cortisol and returned the cortisol to the perfusate. In contrast, guinea pig isolated perfused lungs had neglible effect on cortisone. Rat lungs demonstrated only a limited ability to convert 3-H-cortisol to cortisone. The results suggest that the lungs may play an important role in maintaining cortisone/cortisol levels in the plasma.