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

Aboelnazar, N.; Himmat, Sayed; Hatami, Sanaz; White, Christopher W.; Burhani, Mohamad S.; Dromparis, Peter; Matsumura, Nobutoshi; Tian, Ganghong; Dyck, Jason R.B.; Mengel, Michael; Freed, Darren H.; Nagendran, Jayan

doi:10.1016/j.healun.2017.09.007

Cited by 42 publications

(47 citation statements)

References 39 publications

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“…As seen in our previous experiments, TNF‐α levels rose significantly in the initial part of the experiment then began to recede over time . TNF‐α concentrations were significant lower in the in the TPN group over time (Figure C, P = .02).…”

Section: Resultssupporting

confidence: 78%

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Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Buchko

Stewart

Hatami

et al. 2019

American Journal of Transplantation

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Ex vivo lung perfusion (EVLP) protocols generally limit metabolic supplementation to insulin and glucose. We sought to determine whether the addition of total parenteral nutrition (TPN) would improve lung function in EVLP. Ten porcine lungs were perfused using EVLP for 24 hours and supplemented with insulin and glucose. In the treatment group (n = 5), the perfusate was also supplemented with a continuous infusion of TPN containing lipids, amino acids, essential vitamins, and cofactors. Physiologic parameters and perfusate electrolytes were continuously evaluated. Perfusate lactate, lipid and branch chain amino acid (BCAA) concentrations were also analyzed to elucidate how substrates were being utilized over time. Lungs in the TPN group exhibited significantly better oxygenation. Perfusate sodium was more stable in the TPN group. In the control group, free fatty acids (FFA) were quickly depleted, reaching negligible levels early in the perfusion. Alternatively, BCAA in the control group rose continually over the perfusion demonstrating a shift toward proteolysis for energy substrate. In the TPN group, both FFA and BCAA concentrations remained stable at in vivo levels after initial stabilization. TNF‐α concentrations were lower in the TPN group. The addition of TPN in EVLP allows for better electrolyte composition, decreased inflammation, and improved graft performance.

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Section: Resultssupporting

confidence: 78%

“…Lung procurement and negative pressure ventilation (NPV)‐EVLP was performed as previously described . The animals were sedated with ketamine (20 mg/kg), atropine sulfate (0.05 mg/kg), and xylazine (0.9 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Buchko

Stewart

Hatami

et al. 2019

American Journal of Transplantation

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“…Subgroup analysis revealed downregulated/injury 6‐gene set expression to be reduced to a significantly greater extent with cellular perfusates, suggesting that they may offer further benefit over acellular solutions. Although no clear difference was identified between ventilation strategies in the current study, another recent study by our group, which included 32 porcine and 6 human lungs treated with EVLP, demonstrated significantly less pro‐inflammatory cytokine production ( P < .05), edema ( P < .01), and bullae formation ( P = .02) with NPV vs PPV . A major difference between these 2 studies is that they assessed distinct cohorts of organs.…”

Section: Discussionmentioning

confidence: 55%

“…Clinical success has been achieved with multiple distinct EVLP protocols utilizing different perfusate solutions, flow rates, left atrium models, respiratory rates, and oxygen concentrations . Various experimental protocols, including longer durations and novel ventilation strategies, have also been described. Determining the optimum protocol for EVLP remains an ongoing topic of research and debate.…”

Section: Discussionmentioning

confidence: 99%

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Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs

Dromparis

Aboelnazar

Wagner

et al. 2019

American Journal of Transplantation

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Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex vivo repair remain poorly understood. We aimed to assess the utility of gene expression for characterizing ALI during EVLP. One hundred sixty-nine porcine lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11) hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12 (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies. The expression of 53 previously described ALI-related genes was measured and correlated with function and histology. Twenty-eight genes were significantly upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets demonstrated differential expression with EVLP (P < .001) but not CSP. Upregulated 28-gene set expression peaked after 6 hours of EVLP, whereas downregulated 6-gene set expression continued to decline after 12 hours. Cellular perfusates demonstrated a greater reduction in downregulated 6-gene set expression vs acellular perfusate (P < .038). Gene set expression correlated with relevant functional and histologic parameters, including P/F ratio (P < .001) and interstitial inflammation (P < .005). Further studies with posttransplant results are warranted to evaluate the clinical significance of this novel molecular approach for assessing organ quality during EVLP.

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Ex Vivo Lung Perfusion: Promises and Reality

Noda¹,

Sánchez²

2021

Contemporary Lung Transplantation

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

Cited by 42 publications

References 39 publications

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation

Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs

Ex Vivo Lung Perfusion: Promises and Reality

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