A comparison of the new preservation solution Celsior to Euro-Collins and University of Wisconsin solutions in lung reperfusion injury

BACKGROUND: The lung is particularly susceptible to reperfusion injury, both experimentally and clinically after transplantation. The extracellular-type preservation solution Celsior, which has been predominantly studied in cardiac preservation, has components designed to prevent cell swelling, free radical injury, energy depletion, and calcium overload. Using an isolated blood-perfused rat lung model, we investigated whether Celsior would decrease preservation injury and improve lung function after cold ischemic storage and reperfusion compared to Euro-Collins (EC) and University of Wisconsin (UW) solutions. METHODS: Lewis rat lungs were isolated, flushed with the respective cold preservation solution, and then stored at 4 degrees C for 6 or 12 hr. After ischemic storage, the lung block was suspended from a force transducer, ventilated with 100% O2, and reperfused for 90 min with fresh blood via a cannula in the pulmonary artery. Lung compliance, alveolar-arterial oxygen difference, and outflow oxygen tension were all measured. The capillary filtration coefficient (Kf), a sensitive measure of changes in microvascular permeability, was determined. RESULTS: For 6 hr of cold storage, lungs stored in Celsior had lower Kf values than those stored in EC, indicating decreased microvascular permeability. No other significant differences were noted between Celsior and EC or UW. For 12 hr of cold storage, Celsior provided increased oxygenation, decreased alveolar-arterial O2 differences, increased compliance, and decreased Kf values as compared to both EC and UW. CONCLUSIONS: Celsior provides better lung preservation than EC or UW as demonstrated by increased oxygenation, decreased capillary permeability, and improved lung compliance, particularly at 12-hr storage times. These results are highly relevant, inasmuch as EC and UW are the most common clinically used lung preservation solutions. Further studies of Celsior in experimental and clinical lung transplantation, as well as in other solid organs, are indicated.     

Clinical evaluation of single-tooth restorations supported by osseointegrated implants: a retrospective study

Unilateral whole lung lavage (UWLL) was performed four times in a patient with pulmonary alveolar proteinosis. PaO2 was 94 Torr even under ventilation with 100% O2. Because of the difficulty in providing adequate arterial oxygenation, extracorporeal membrane oxygenation (ECMO) was indispensable in accomplishing the first right UWLL. During the second left UWLL, the left lung was ventilated with nitrogen (N2) and an attempt was made to predict the lowest PaO2 occurring during lavage in order to establish criteria for the use of ECMO during UWLL. When both lungs were ventilated with 100%. O2, PaO2 rose to 150 Torr. PaO2 fell to 65 Torr after ventilation of the left lung with N2 while the right lung was ventilated with 100% O2 for 7 minutes. The N2 was replaced with 100% O2 and ventilation was continued for another 10 minutes to wash the N2 out of the left lung. When the tracheal tube in the left lung was clamped for 7 minutes for degassing, PaO2 fell to 59 Torr. Subsequently 1,200 ml of physiological saline was injected into the left lung, and PaO2 rose to 155 Torr. A 6 Torr difference was found between the value of PaO2 under ventilation with N2 and that of degassing, but this difference was not statistically significant. The lowest PaO2 occurring during UWLL was considered to be predictable if the unilateral lung was ventilated with N2.     

Canine lung transplantation after more than twenty-four hours of normothermic preservation

BACKGROUND: Consistent clinical results have not been achieved when lung preservation times exceed 6 hours. The aim of this study was to use an alternative normothermic autoperfusion technique for lung preservation and transplantation. METHODS: In six paired dogs, donor lungs were removed, along with the heart, liver, pancreas, duodenum, and both kidneys, and were preserved for 24 to 33 hours in a normothermic autoperfused multiple organ block. Orthotopic left lung transplantation was performed at the end of the preservation period. RESULTS: Lung function was good during the preservation period. With a gas mixture of 50% O2 + 3% CO2 + 47% N2 delivered to the multiorgan block, arterial oxygen tension ranged from 331 +/- 19 to 383 +/- 8 mm Hg; carbon dioxide tension ranged from 18 +/- 5 to 32 +/- 5 mm Hg; and pH ranged from 7.36 +/- 0.02 to 7.45 +/- 0.08. After transplantation, the dogs were kept anesthetized and ventilated for 24 hours with the same gas mixture. The opposite pulmonary artery was occluded 0 to 6 hours after transplantation. Arterial blood pressures were stable after surgery. Arterial oxygen tension was maintained between 205 +/- 39 and 320 +/- 57 mm Hg, and arterial carbon dioxide tension was maintained between 23 +/- 2 and 34 +/- 2 mm Hg. Lung tissue wet/dry weight ratio was 4.94 +/- 0.17 after preservation; this ratio did not differ from that found in normal controls (4.91 +/- 0.10). CONCLUSIONS: This study shows that the lungs were well preserved for more than 24 hours of preservation when the normothermic multiorgan block preparation was used. The transplanted left lung was able to support the anesthetized dog after the opposite pulmonary artery was occluded.     

Alveolar expansion itself but not continuous oxygen supply enhances postmortem preservation of pulmonary grafts

OBJECTIVE: If lungs could be retrieved for transplant after circulatory arrest, the shortage of donors might be significantly alleviated. Great controversy still exists concerning the optimal mode of preservation of pulmonary grafts in these non-heart-beating donors. METHODS: Graft function was measured in an isolated room air-ventilated rabbit lung model during reperfusion with homologous, diluted (Hb +/- 8.0 g/dl) and deoxygenated (PaO2 +/- 40 mmHg) blood up to 4 h. Five groups of cadavers (n = 4 in each group) were studied: In the control group, lungs were immediately reperfused. In the other groups, cadavers were left at room temperature for 4 h after death with lungs either deflated (group 1), inflated with room air (group 2), or ventilated with room air (group 3) or 100% nitrogen (group 4). RESULTS: After 1 h of reperfusion, significant differences were noted between group 1 and groups 2, 3, and 4 in peak airway pressure (27 +/- 5 cm H2O vs. 15 +/- 1 cm H2O, 17 +/- 2 cm H2O, and 16 +/- 1 cm H2O, respectively; P < 0.05), in weight gain (137 +/- 24 vs. 31 +/- 7, 30 +/- 3, and 30 +/- 2%, respectively; P < 0.05), and in veno-arterial oxygen pressure gradient (9 +/- 5 vs. 95 +/- 13, 96 +/- 7 and 96 +/- 4 mmHg, respectively; P < 0.05). Also, wet-to-dry weight ratio at end of reperfusion was significantly different (10.2 +/- 1.0 vs. 6.0 +/- 0.3. 5.2 +/- 0.3 and 5.4 +/- 0.5, respectively; P < 0.05). No significant differences in any of these parameters were observed between groups 2, 3, and 4. CONCLUSIONS: These data suggest that: (1) pulmonary edema will develop in atelectatic lungs if reperfusion is delayed for 4 h after death; (2) postmortem room air-inflation is as good as ventilation in prolonging warm ischemic tolerance; (3) ventilation with room air is no different from that with nitrogen; (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the warm ischemic lung from reperfusion injury independent of continuous oxygen supply.     

Resection hip arthroplasty for malignant pelvic tumor. Outcome in 5 patients followed more than 2 years

BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some properties that provide protection from lung injury. Furthermore, its protective effect in cold storage of donor lungs has been confirmed. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution, and orthotopic left lung transplantations were performed. Rats were divided into four groups (n = 6). Group I received no preservation or storage. Groups II, III, and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP. Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial O2 tension values of groups III and IV were better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8, 373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3 +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01). Wet-dry weight ratio in group III was lower than in groups II and IV (group II, III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147, and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion injury in an in vivo rat lung transplantation model. Either administration of VIP via the flush solution or systemically just after reperfusion was associated with improved pulmonary function.     

High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alpha2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.     

Lung preservation with low-potassium dextran flush in a primate bilateral transplant model

We used a bilateral lung transplant model to confirm, in primates, the results of lung preservation studies previously obtained in a canine single-lung transplant model. The donor lungs were flushed with low-potassium dextran solution and maintained semiinflated with 100% oxygen at 10 degrees C for a planned ischemic time of 12 hours for the lung implanted first. Of eight experiments performed, results in the 6 operative survivors form the basis of this report. After bilateral lung transplantation, animals were maintained on a ventilator for 6 hours; arterial oxygen tension, pulmonary artery pressure, and pulmonary vascular resistance were determined in the recipients at 2, 4, and 6 hours after transplantation and compared with donor values, which served as controls. Arterial oxygen tension in the recipients did not differ from the controls (p = not significant), whereas the pulmonary artery pressure and pulmonary vascular resistance showed significant elevation (p < 0.05 versus control values). After the 6 hours of assessment, the animals were extubated and 3 survived for 48 to 72 hours with a mean arterial oxygen tension of 69 mm Hg on room air. These results demonstrate excellent lung function after a minimum of 12 hours of preservation in a primate model in which the animal is totally dependent on the function of transplanted lung tissue, and confirm the potential for prolonged clinical lung preservation.     

Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Peak airway pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and wet to dry weight ratio were measured during delayed hypothermic crystalloid flush in rabbit lungs (n = 6) at successive intervals after death comparing cadavers with lungs left deflated (group 1), inflated with room air (group 2) or 100% oxygen (group 4), or ventilated with room air (group 3), or 100% nitrogen (group 5), or 100% oxygen (group 6). RESULTS: There was a gradual increase in mean pulmonary artery pressure and pulmonary vascular resistance with longer postmortem intervals in all study groups (p = not significant, group 1 versus group 2 versus group 3). There was also a gradual increase in peak airway pressure and wet-to-dry weight ratio over time in all groups, which reflected edema formation during flush (airway pressure, from 14.5 +/- 1.0 cm H2O to 53.7 +/- 12.2 cm H2O, and wet-to-dry weight ratio, from 3.6 +/- 0.1 to 11.5 +/- 1.2, in group 1 at 0 and 6 hours postmortem, respectively; p < 0.05). Compared with group 1, however, the increase in groups 2 and 3 was much slower (airway pressure, 20.9 +/- 0.5 cm H2O and 18.8 +/- 1.2 cm H2O, and wet-to-dry weight ratio, 5.2 +/- 0.3 and 4.6 +/- 0.4 at 6 hours postmortem, respectively; p < 0.05 versus group 1 and p = not significant, group 2 versus group 3). Airway pressure and wet-to-dry weight ratio did not differ between groups 2 and 4 or between groups 3, 5, and 6. CONCLUSIONS: These data suggest that (1) pulmonary edema will develop in atelectatic lungs if hypothermic flush is delayed for 2 hours after death, (2) postmortem inflation is as good as ventilation in prolonging warm ischemic tolerance, (3) inflation with oxygen or ventilation with nitrogen or oxygen is no different from that with room air, and (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the lung from warm ischemic damage independent of continued oxygen delivery.     

Low-dose sodium nitroprusside reduces pulmonary reperfusion injury

BACKGROUND: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension. METHODS: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.     

Effect of hypotension preceding death on the function of lungs from donors with nonbeating hearts

BACKGROUND: A shortage of suitable brain-dead donors continues to severely limit lung transplantation. Use of donors with nonbeating hearts has been suggested as a solution. Lungs are unique, in that aerobic metabolism can continue in the absence of blood circulation because oxygen is present in airways and alveoli. Animal studies have shown reasonable cadaveric graft function up to several hours after sudden death by drug administration. However, hemodynamic instability before death may worsen lung function through activation and pulmonary sequestration of neutrophils and release of inflammatory mediators. Because many potential cadaveric donors experience hypotension before death, this study was undertaken to assess the effect of hypotensive shock on cadaveric lung viability. METHODS: A rat isolated lung reperfusion model was used to assess pulmonary function over 3 hours of reperfusion or until gross pulmonary edema developed. Twenty-five rats were randomly allocated to the following study groups, which were based on status before lung harvest: (1) control: no interventions; (2) hypotensive: 1 hour of hypotension by exsanguination to a mean blood pressure of 30 to 40 mm Hg; (3) cadaver: death by cervical dislocation followed by 3 hours of in situ lung ischemia; (4) hypotensive + 3 hours cadaver: 1 hour of hemorrhagic shock, followed by death and 3 hours of in situ ischemia; (5) hypotensive + 2 hours cadaver: similar to group 4, except the in situ ischemia was abbreviated to 2 hours. RESULTS: No significant differences were found among group 1, 2, or 3 lungs with regard to wet to dry weight ratios, gas exchange, and pulmonary arterial or airway pressures. However, all group 4 lungs became grossly hemorrhagic and developed severe pulmonary edema within 10 minutes of reperfusion. Group 5 lungs fared only marginally better, with two of five lungs tolerating 3 hours of reperfusion. CONCLUSIONS: A period of hypotension before death severely impairs cadaveric lung viability.     

Enhancement of extended lung preservation with a vasoactive intestinal peptide-enriched University of Wisconsin solution

Vasoactive intestinal peptide (VIP) is a known pulmonary and bronchial vasodilator as well as an oxygen free radical scavenger. Since its effect as an additive to University of Wisconsin (UW) solution for lung preservation has been shown previously, the aim of this study was to determine the ability of VIP to improve lung preservation followed by reperfusion. Four groups of excised Sprague-Dawley rat lungs (n = 24) were studied using an isolated blood perfused working lung model. The first 3 groups of lungs were flushed and stored in UW solution at 4 degrees C for: (1) 4 hr, (2) 18 hr, and (3) 24 hr. Group 4 lungs were flushed with UW solution + VIP (1 microgram/ml) and stored in UW solution + VIP (0.5 microgram/ml) for 24 hr. After preservation, the lungs were reperfused to evaluate their functions for 2 hr or until lung failure occurred (arterial oxygen saturation less than 90% and/or appearance of bronchial fluid in the bronchial cannula). In the lungs stored in UW solution for 24 hr, failure occurred after 10 min of reperfusion and all functions were significantly altered. The addition of VIP to UW solution maintained the functional capacity of the lungs, recorded by lung resistance, lung compliance, elastic work, flow resistive work, shunt fraction, and blood oxygen tension. No statistical difference in these parameters other than shunt fraction was found when the VIP group was compared with the group preserved for 4 hr in UW solution. We conclude that lung preservation can be extended to 24 hr with the maintenance of lung functional capacity if VIP is added to UW solution.     

Cellular distribution of pulmonary Mn and CuZn superoxide dismutase: effect of hyperoxia and interleukin-1

Pulmonary superoxide dismutase (SOD) plays an important role in the lung defense against O2 toxicity. We have previously demonstrated that tracheal insufflation of interleukin-1 alpha (IL-1) selectively enhances pulmonary MnSOD and protects rats against O2 toxicity. However, little is known about the cellular distribution of pulmonary MnSOD- and CuZnSOD-specific proteins. We performed immunohistochemistry in plastic sections (2 microns thick) to determine the effects of hyperoxia and IL-1 on the cellular distribution of pulmonary MnSOD and CuZnSOD in rats. MnSOD and CuZnSOD were present in all lung cells. Smooth muscle and endothelial cells appeared to contain higher immunoreactive MnSOD and CuZnSOD proteins than other lung cell types. Exposure of rats to 100% O2 for 24 hr had no effect on the cellular distribution and intensity of pulmonary MnSOD. However, at 50 hr after O2 exposure the intensity of pulmonary MnSOD was reduced. In contrast, tracheal insufflation of IL-1 markedly enhanced the intensity of pulmonary MnSOD in rats exposed to O2 for 50 hr. Neither O2 exposure nor IL-1 insufflation had any apparent effect on the distribution and intensity of pulmonary CuZnSOD. We conclude that IL-1 selectively enhances pulmonary MnSOD and that this effect is manifested in most lung cells, particularly smooth muscle and endothelial cells.     

Pulmonary function after one-lung ventilation in newborns: the basis for neonatal thoracoscopy

BACKGROUND: To maintain good exposure during major video-assisted thoracic surgery it is necessary to deflate completely the ipsilateral lung. However, little is known about the effects of one-lung ventilation (OLV) on pulmonary function in newborn patients. METHODS: Ten neonatal domestic pigs with a mean age of 6+/-0.6 days were intubated and ventilated in pressure-controlled mode (inspired oxygen fraction=1.0). One-lung ventilation was maintained for 120 minutes. Serial measurements of hemodynamics and gas exchange were done before, during, and until 90 minutes after OLV. Pulmonary function testing was performed before and after OLV for each lung separately. RESULTS: With the inspired oxygen fraction set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar-arterial oxygen tension gradient increased slightly from the baseline value of 2.6% +/-0.3% to 3.8%+/-0.3% during OLV (mean+/-standard error of the mean; p=0.02), and from 358+/-28 to 407+/-18 mm Hg (not significant), respectively. Both values returned to baseline during the subsequent ventilation of both lungs. Static compliance and resistance of the ventilated lung did not change. Compliance of the collapsed lung decreased after reexpansion from 0.42+/-0.07 to 0.29+/-0.06 mL x cm H2O(-1) x kg(-1), p=0.008). Resistance remained unchanged (0.22+/-0.02 versus 0.25+/-0.05 cm H2O x L(-1) x s(-1); not significant). CONCLUSIONS: There were only minor effects on pulmonary function during and after OLV in the neonatal piglet. Alterations in gas exchange during OLV were minimal. Prolonged collapse of the lung with subsequent reexpansion was associated with a slight decrease in compliance, indicating some mild lung injury.     

Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs

Ventilation during ischemia attenuates ischemia-reperfusion lung injury, but the mechanism is unknown. Increasing tissue cyclic nucleotide levels has been shown to attenuate lung ischemia-reperfusion injury. We hypothesized that ventilation prevented increased pulmonary vascular permeability during ischemia by increasing lung cyclic nucleotide concentrations. To test this hypothesis, we measured vascular permeability and cGMP and cAMP concentrations in ischemic (75 min) sheep lungs that were ventilated (12 ml/kg tidal volume) or statically inflated with the same positive end-expiratory pressure (5 Torr). The reflection coefficient for albumin (sigmaalb) was 0.54 +/- 0.07 and 0.74 +/- 0. 02 (SE) in nonventilated and ventilated lungs, respectively (n = 5, P < 0.05). Filtration coefficients and capillary blood gas tensions were not different. The effect of ventilation was not mediated by cyclic compression of alveolar capillaries, because negative-pressure ventilation (n = 4) also was protective (sigmaalb = 0.78 +/- 0.09). The final cGMP concentration was less in nonventilated than in ventilated lungs (0.02 +/- 0.02 and 0.49 +/- 0. 18 nmol/g blood-free dry wt, respectively, n = 5, P < 0.05). cAMP concentrations were not different between groups or over time. Sodium nitroprusside increased cGMP (1.97 +/- 0.35 nmol/g blood-free dry wt) and sigmaalb (0.81 +/- 0.09) in nonventilated lungs (n = 5, P < 0.05). Isoproterenol increased cAMP in nonventilated lungs (n = 4, P < 0.05) but had no effect on sigmaalb. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester had no effect on lung cGMP (n = 9) or sigmaalb (n = 16) in ventilated lungs but did increase pulmonary vascular resistance threefold (P < 0.05) in perfused sheep lungs (n = 3). These results suggest that ventilation during ischemia prevented an increase in pulmonary vascular protein permeability, possibly through maintenance of lung cGMP by a nitric oxide-independent mechanism.     

Warm ischemic tolerance in collapsed pulmonary grafts is limited to 1 hour

OBJECTIVE: To determine the length of warm ischemic tolerance in pulmonary grafts from non-heart-beating donors. SUMMARY BACKGROUND DATA: If lungs could be retrieved for transplant after circulatory arrest, the shortage of donors might be significantly alleviated. Great concern, however, exists about the length of tolerable warm ischemia before cold preservation of pulmonary grafts retrieved from such non-heart-beating donors. METHODS: The authors compared the influence of an increasing postmortem interval on graft function in an isolated, room air-ventilated rabbit lung model during blood reperfusion up to 4 hours. Four groups of cadavers (four animals per group) were studied. In group 1, lungs were immediately reperfused. In the other groups, cadavers with lungs deflated were left at room temperature for 1 hour (group 2), 2 hours (group 3), or 4 hours (group 4). RESULTS: Pulmonary vascular resistance was enhanced in all ischemic groups compared with the control group. An increase was noted with longer postmortem intervals in peak airway pressure and in weight gain. A concomitant decline was observed in the venoarterial oxygen pressure gradient caused by progressive edema formation, as reflected by the wet-to-dry weight ratio at the end of reperfusion. CONCLUSIONS: Warm ischemia resulted in increased pulmonary vascular resistance. Graft function in lungs retrieved 1 hour after death was not significantly worse than in nonischemic lungs. Therefore, 60 minutes of warm ischemia with the lung collapsed may be tolerated before cold storage. Further studies are necessary to investigate whether lungs retrieved from non-heart-beating donors will become a realistic alternative for transplant.     

A prospective evaluation of children under the age of 5 years living in the same household as adults with recently diagnosed pulmonary tuberculosis

Lung injury is a well-documented adverse effect of cardiopulmonary bypass. The mechanism of injury is not fully understood, but pulmonary hypoxia may be a factor. Post-operative pulmonary epithelial permeability (PEP) in ventilated versus non-ventilated lungs was measured within 2 h of return to the intensive care unit using a 99Tcm-diethylenetriamine pentaacetate aerosol technique. A portable scintillation detector system was required. Sodium iodide detectors have been used previously with this technique but are cumbersome. This study used mini caesium iodide detectors (Oakfield Instruments, Oxon, UK), which can be attached directly to the patient and are more suited to the intensive care setting. The clearance half-time from lung to blood (T1/2LB) was measured in 31 patients (62 lungs). The mean (+/- S.E.M.) clearance half-times were 42.3 +/- 2.7 and 45.7 +/- 3.8 min for non-ventilated and ventilated lungs respectively, with a mean difference of 3.4 +/- 3.1 min (P > 0.05). We conclude that, using this technique, no significant difference in PEP is observed between ventilated and non-ventilated lungs in patients undergoing cardiopulmonary bypass.     

Pattern of injury and the role of neutrophils in reperfusion injury of rat lung

Using a rat lung model, we sought to characterize the time course for ischemia-reperfusion injury and the role of neutrophils in the development of injury. Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, and vein for 90 min, resulting in complete left lung ischemia. The lungs were then ventilated and reperfused for up to 4 hr. Time-matched sham animals underwent the identical thoracotomy and hilar dissection, but the lungs were not rendered ischemic. Using vascular permeability of 125I-labeled bovine serum albumin as a measure of reperfusion injury, a bimodal pattern of injury was observed. Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant early phase of lung injury at 30 min of reperfusion (P < 0.0001), followed by partial recovery. A second peak of lung injury was noted after 4 hr of reperfusion (P < 0.001). Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course. To determine the role of neutrophils in the development of lung reperfusion injury, additional animals undergoing the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operation. Profound neutropenia (< 75/mm3 blood) was confirmed by differential leukocyte counts. Neutropenia had no protective effect against microvascular permeability at 30 min of reperfusion, but there was a significant reduction in lung injury at 4 hr (P < 0.005). We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury, consisting of both neutrophil-independent and neutrophil-mediated events.     

Does the mode of donor death influence the early outcome of lung transplantation? A review of lung transplantation from donors involved in major trauma

BACKGROUND: Pulmonary dysfunction, often delayed in presentation, is among the sequelae of major trauma. Transplantation of lungs from donors involved in major trauma therefore carries a risk of early graft dysfunction. This study was conducted to assess this risk. METHODS: A retrospective comparison of the outcome from 123 donors (57 donors resulting from major trauma, group T, and 66 donors with nontraumatic origin, group NT) in 125 consecutive technically successful lung or heart-lung transplantations. Variables analyzed included the following: clinical and bacteriologic details of donors and indexes of early graft dysfunction in the recipients. RESULTS: Group T donors were more likely to be younger and male (p < 0.05) and more likely to have had lung ventilation for over 48 hours (p < 0.05) than group NT donors. Microbial contamination of routine donor bronchial lavage (72 of 122, 61%) was no higher in group T (34 of 57, 60%), but, in this group, enteric gram-negative bacilli were more common (30% versus 7%; p < 0.05). Male patients were more likely to receive lungs from group T donors (35 male, 23 female), and female patients were more likely to receive lungs from group NT donors (27 male, 40 female). Mode of donor death did not affect the following indexes of early graft function: length of postoperative ventilation, ratio of arterial oxygen tension to fractional concentration of inspired oxygen at 1 or 24 hours after transplantation, or the incidence of diffuse alveolar damage in lung biopsy specimens at 7 days. Thirty-day mortality (28%) was no higher among recipients of group T lungs, but six recipient deaths were donor-related (donor-transmitted pneumonia in five and donor acquired fat embolism in one case). CONCLUSION: The use of donors involved in major trauma does not increase the risk of early complications after lung transplantation providing their specific characteristics are recognized.     

Chlorine gas induced acute lung injury in isolated rabbit lung

This study was designed to investigate the pathogenesis of chlorine gas (Cl2) induced acute lung injury and oedema. Isolated blood-perfused rabbit lungs were ventilated either with air (n=7) or air plus 500 parts per million (ppm) of Cl2 (n=7) for 10 min. Capillary pressure, measured by analysing the pressure/time transients of pulmonary arterial, venous and double (both arterial and venous) occlusions, was unchanged in both groups. In Cl2-exposed lungs, the fluid filtration rate increased from -0.228+/-0.25 to 1.823+/-1.23 mL min(-1) x 100 g(-1) (p<0.001) and the filtration coefficient increased from 0.091+/-0.01 to 0.259+/-0.07 mL x min(-1) x cmH2O(-1) x 100 g(-1) (p<0.001). No changes were observed in the control lungs. The extravascular lung water/blood-free dry weight ratio was 8.6+/-1.6 in the Cl2 group and 4.0+/-0.5 in the control group (p<0.001), confirming that the increase in lung weight was related to accumulation of extravascular fluid. Although the alveolar flooding by oedema is explained, in part, by the Cl2-induced epithelial injury, our results suggest that Cl2 exposure induces acute lung injury and oedema due to an increased microvascular permeability.