Perfusate Exchange Does Not Improve Outcomes in 24-hour Ex Situ Lung Perfusion.

Reliable 24-hour preservation is required to optimize the rehabilitation potential of Ex Situ Lung Perfusion (ESLP). Other ESLP protocols include fresh perfusate replacement to counteract an accumulation of deleterious by-products. We describe the results of our reliable 24-hour negative pressure ventilation (NPV)-ESLP protocol with satisfactory acute post-transplant outcomes and investigate perfusate exchange (PE) as a modification to enhance prolonged ESLP. Twelve pig lungs underwent 24 hours of NPV-ESLP using 1.5L of cellular perfusate (500 mL packed red blood cells and 1 L buffered perfusate). The Control (n = 6) had no PE; the PE (n = 6) had 500 mL replaced after 12 hours of NPV-ESLP with 1000 mL fresh perfusate. Three left lungs per group were transplanted. Results are reported as Control vs PE (mean ± SEM). Both groups demonstrated stable and acceptable oxygenation during 24 hours of ESLP with final PF ratios of 527.5 ± 42.19 and 488.4 ± 35.38 (P = .25). Final compliance measurements were 20.52 ± 3.59 and 18.55 ± 2.91 (P = .34). There were no significant differences in pulmonary artery pressure after 24 hours of ESLP (10.02 ± 2.69 vs 14.34 ± 1.64, P = .10), and pulmonary vascular resistance only differed significantly at T12 (417.6 ± 53.06 vs 685.4 ± 81.19, P = .02). Percentage weight gain between groups was similar (24.32 ± 8.4 and 45.33 ± 7.76, P = .07). Post-transplant left lung oxygenation was excellent (327.3 ± 14.62 and 313.3 ± 15.38, P = .28). There was no significant difference in % weight gain of lungs post-transplant (22.20 ± 7.22 vs 14.36 ± 9.96, P = .28). Acceptable lung function was maintained during 24-hour NPV-ESLP and post-transplant regardless of PE.

Forgie K ，Watkins A ，Du K ，Ribano A ，Fialka N ，Himmat S ，Hatami S ，Khan M ，Wang X ，Edgar R ，Buswell-Zuk KM ，Freed DH ，Nagendran J ... -  《-》

Moderate-Flow Perfusion is Superior to Low-Flow Perfusion in Ex Situ Lung Perfusion.

Forgie K ，Fialka N ，Watkins A ，Du K ，Himmat S ，Hatami S ，Khan M ，Wang X ，Edgar R ，Buswell-Zuk KM ，Freed D ，Nagendran J ... -  《-》

Normothermic Perfusion is Superior to Cold Perfusion in Porcine Ex Situ Lung Perfusion.

Cold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model. Four perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model. Pig lungs were allotted to four groups: (1) Normothermia (38°C, n = 6); (2) profound hypothermia (10°C, n = 6); (3) moderate hypothermia (20°C, n = 3); (4) subnormothermia (32°C, n = 3). A fifth group subnormothermic low-flow (SNLF) perfusion was examined to assess the effect of reduced cardiac output with cold perfusion (32°C, 10% cardiac output, n = 6). Only Normothermic and SNLF groups demonstrated acceptable oxygenation after 12 hours NPV-ESLP and were transplanted. All other groups failed prematurely. After 12 hours of ESLP, Normothermic lungs demonstrated significantly greater dynamic compliance compared to SNLF lungs (P = .03). Edema formation post-ESLP was significantly worse in the SNLF group (P = .01). There was no significant difference in pulmonary artery pressures after ESLP (P = .10); however, pulmonary vascular resistance was significantly greater in the SNLF (P = .04). Isolated left lung oxygenation 4-hours post-transplant and left lung edema formation was not significantly different between Normothermic and SNLF post-transplant (P = .09). Proinflammatory cytokines were significantly greater during SNLF-ESLP (tumor necrosis factor alpha, P < .05). Prolonged normothermic (38°C) NPV-ESLP is superior to 10, 20, and 32°C perfusion. Normothermic ESLP of porcine lungs results in superior graft function and reduced inflammation versus SNLF-ESLP.

Forgie K ，Fialka N ，Watkins A ，Du K ，Himmat S ，Hatami S ，Khan M ，Wang X ，Edgar R ，Buswell-Zuk KM ，Freed DH ，Nagendran J ... -  《-》

Normothermic Negative Pressure Ventilation Ex Situ Lung Perfusion: Evaluation of Lung Function and Metabolism.

Forgie KA ，Fialka N ，Buchko M ，Himmat S ，Hatami S ，Qi X ，Wang X ，Buswell KM ，Edgar R ，Freed DH ，Nagendran J ... -  《Jove-Journal of Visualized Experiments》

Negative pressure ventilation decreases inflammation and lung edema during normothermic ex-vivo lung perfusion.

Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC). The impact of ventilation strategy on the preservation of 6 unutilized human donor lungs was also evaluated. Physiologic parameters, cytokine profiles, lung injury, bullae and edema formation were compared between treatment groups. Perfused lungs demonstrated acceptable oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen ratio >350 mm Hg) and physiologic parameters. However, there was less generation of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interleukin-8) in human and pig lungs perfused, irrespective of perfusate solution used, when comparing NPV with PPV (p < 0.05), and a reduction in bullae formation with an NPV modality (p = 0.02). Pig lungs developed less edema with NPV (p < 0.01), and EVLP using an acellular perfusate solution had greater edema formation, irrespective of ventilation strategy (p = 0.01). Interestingly, human lungs perfused with NPV developed negative edema, or "drying" (p < 0.01), and lower composite acute lung injury (p < 0.01). Utilization of an NPV strategy during extended EVLP is associated with significantly less inflammation, and lung injury, irrespective of perfusate solution composition.

Aboelnazar NS ，Himmat S ，Hatami S ，White CW ，Burhani MS ，Dromparis P ，Matsumura N ，Tian G ，Dyck JRB ，Mengel M ，Freed DH ，Nagendran J ... -  《-》