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Background: Mature lobar transplantation will increase the pediatric donor organ pool; however, issues regarding size discrepancy between donor grafts and recipient lungs remain unresolved. We hypothesized that an oversized mature pulmonary lobar allograft implanted into an immature recipient would provide adequate longterm pulmonary function versus a size-matched mature lobar graft or an immature whole lung., Methods: We investigated our hypothesis in a porcine orthotopic left lung transplant model in which 19 immature animals made up one control and three recipient groups. Group I underwent sham left thoracotomy (control, n = 4). Group II received age- and size-matched immature whole left lung transplant (n = 6). Group III received mature size-matched left upper lobe transplants (n = 4). Group IV received mature over-sized left lower lobe transplants (n = 5). Twelve weeks after implantation, data were collected after the native right lung was excluded., Results: Graft weight was significantly elevated in group IV as compared with the explanted lung (72.4 +/- 6.8 versus 38.3 +/- 4.5 g; p = 0.003). Pulmonary artery pressure and pulmonary vascular resistance were significantly elevated in group III as compared with the over-sized mature lower lobe transplants (51.8 +/- 2.2 versus 40.4 +/- 2.5 mm Hg [p < 0.0001] and 1,605.9 +/- 117.5 versus 857.6 +/- 133.6 dynes.s.cm-5 [p < 0.0005], respectively). A trend toward decreased oxygenation was identified in group II., Conclusions: Over-sized mature lobar grafts provide improved hemodynamics as compared with size-matched grafts. Mature left lower lobe grafts are superior to size-matched upper lobe grafts in this model, probably as a result of an augmented vascular bed.

Background: Decreased airway compliance after lung transplantation has been observed with severe ischemia-reperfusion injury. Further, it has been shown that the surfactant system is impaired after lung preservation and reperfusion. We hypothesized that surfactant replacement after allograft storage could preserve airway compliance during reperfusion., Methods: Rabbit lungs were harvested after flush with 50 mL/kg of cold saline solution. Immediate control lungs were studied with an isolated ventilation/perfusion apparatus using venous rabbit blood recirculated at 40 mL/min, room-air ventilation at 20 breaths/min, and constant airway pressure (n = 8). Twenty-four-hour control lungs were preserved at 4 degrees C for 24 hours and then similarly studied (n = 7). Surfactant lungs underwent similar harvest and preservation for 24 hours, but received 1.5 mL/kg of intratracheal surfactant 5 minutes before reperfusion (n = 10). Airway pressure and flow were recorded continuously during 30 minutes of reperfusion. Tidal volume and airway compliance were calculated at 30 minutes., Results: Tidal volume was 33.67 +/- 0.57, 15.75 +/- 5.72, and 29.83 +/- 1.07 mL in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.004, surfactant versus 24-hour control). Airway compliance was 1.94 +/- 0.27, 0.70 +/- 0.09, and 1.46 +/- 0.10 mL/mm Hg in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.002, surfactant versus 24-hour control)., Conclusions: We conclude that surfactant administration before reperfusion after 24 hours of cold storage preserves tidal volume and airway compliance in the isolated ventilated/perfused rabbit model of lung reperfusion injury.

Background: Bronchial viability after lung transplantation remains a concern. Modern preservation methods, surgical technique, and limited cold ischemic periods have decreased the frequency of bronchial complications. However, lungs procured from non-heart-beating donors are subjected to a mandatory period of warm ischemia. We investigated bronchial healing in a porcine survival model of left lung transplantation using organ procurement from non-heart-beating donors after a 60-minute period of warm ischemia., Methods: Fourteen adult domestic swine underwent left lung transplantation. All lungs were preserved with cold Euro-Collins flush and stored inflated at 4 degrees C. Control lungs (n = 5) were flushed, harvested, and stored for 2 hours before implantation. Experimental lungs (n = 9) were procured from non-heart-beating donors. These lungs were subjected to 60 minutes of warm ischemia before flush and harvest, followed by 2 hours of cold storage before implantation. After 21 days of immunosuppression with prednisone, azathioprine, and cyclosporine, pulmonary function was assessed. Bronchial viability was evaluated with bronchoscopy and, at autopsy, followed by histologic analysis., Results: Implantation time did not differ significantly between the control group and the experimental group (59.6 +/- 2.1 versus 64.4 +/- 2.9 minutes, p = 0.24). Control swine exhibited no evidence of ischemic injury to the donor bronchus. In contrast, six of nine lungs procured from non-heart-beating donors showed evidence of ischemic bronchial injury (p = 0.031 versus control). Findings ranged from hypovascular edematous mucosa to necrosis and sloughing of the mucosa throughout the entire donor bronchial tree. The remaining three non-heart-beating donor lungs exhibited normal lung function and bronchial healing., Conclusions: We conclude that 60 minutes of warm ischemia for lungs procured from non-heart-beating donors results in impaired bronchial viability with current preservation techniques. Thirty minutes of warm ischemia may be the acceptable limit for lung procurement from non-heart-beating organ donors.

Background: We previously demonstrated that standard preservation using Euro-Collins solution impairs lung function in the setting of high-flow reperfusion because of potassium-induced vasoconstriction. Preservation strategies for single-lung transplantation are an important factor in patients with pulmonary hypertension. This study investigates the hypothesis that low-potassium preservation solution will improve function of lungs subjected to high-flow reperfusion., Methods: Twenty-one New Zealand white rabbit lungs were harvested and studied on an isolated, blood-perfused model of lung function after 4 hours of cold ischemia at 4 degrees C. Control lungs were preserved with 50 mL/kg of cold saline solution flush (group I). Experimental lungs were preserved with low-potassium solution (group II) or Euro-Collins solution (group III) at similar temperatures and volumes., Results: The pulmonary arteriovenous oxygen gradient at the end of the 30-minute high-flow reperfusion period was significantly higher in group II compared with group III (121.3 +/- 19.2 mm Hg versus 31.1 +/- 4.2 mm Hg; p < 0.001). The pulmonary vascular resistance was significantly lower in group II than in group III (46.3 +/- 1.8 x 10(3) dynes x s x cm(-5) versus 79.8 +/- 8.4 x 10(3) dynes x s x cm(-5); p < 0.01. The percent decrease in dynamic airway compliance in group III was significantly greater than in group I and II (-51.0% +/- 13.3% versus -10.2% +/- 3.4% and -11.2% +/- 2.8%, respectively; p < 0.001). Similarly, the wet to dry ratio of the lungs in group III was significantly greater than in groups I and II (13.9 +/- 2.3 versus 5.9 +/- 0.2 and 6.0 +/- 0.4, respectively; p < 0.001)., Conclusions: These data demonstrate that a low-potassium preservation solution yields improved lung function after high-flow reperfusion in an ex vivo rabbit lung model. Lung preservation should be aimed at the clinical setting.

Background: Lung procurement from recently deceased cadavers has been suggested to enlarge the limited donor pool. We hypothesized that lungs harvested from non-heart-beating donors (NHBD) would function as well as those harvested from heart-beating donors., Methods: Sixteen adult swine underwent left lung allotransplantation. Controls received lungs procured from heart-beating donors, NHBD pigs received lungs immediately harvested from donors after death from asphyxiation, and NHBD-15 and NHBD-30 pigs received lungs harvested after 15 and 30 minutes after asphyxiation., Results: After 1 week of survival, mean dynamic airway compliance (mL/cm H2O +/- standard error of the mean) was 16.3 +/- 0.7 in controls, and 17.3 +/- 1.0, 16.4 +/- 6.0, and 7.3 +/- 1.6 in the NHBD, NHBD-15, and NHBD-30 groups, respectively (p = 0.02, NHBD-30 versus others combined). No significant differences were noted in the pulmonary venous partial pressure of oxygen or pulmonary vascular hemodynamics compared with controls., Conclusions: The decrease in airway compliance noted in the NHBD-30 group may reflect an exacerbation of reperfusion injury caused by 30 minutes of warm ischemia during organ retrieval. We conclude that posttransplantation lung function using an NHBD with up to 15 minutes of warm ischemia is equivalent to lung function after heart-beating harvest.