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Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury.

ABSTRACT: Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury.We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcine model of lung injury. Two groups of 4 animals each received a 2-hour infusion of LPS through the external jugular vein. Serial measurements of blood gases were performed every 30 minutes until the partial pressure of oxygen/fraction of inspired oxygen ratio dropped below 150 on two consecutive readings. Lungs were then randomized to treatment with 4 hours of normothermic EVLP with STEEN Solution (XVIVO Perfusion Inc, Englewood, CO) or 4 additional hours of in vivo perfusion (control). Airway pressures and blood gases were recorded for calculation of dynamic lung compliance and partial pressure of oxygen/fraction of inspired oxygen ratios. EVLP was performed with hourly recruitment maneuvers and oxygen challenge.All animals reached a partial pressure of oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg within 3 hours after start of the LPS infusion. Oxygenation and compliance in the control animals continued to decline during the 4-hour in vivo perfusion period, and 3 of the 4 animals died of severe hypoxia within 4 hours. The EVLP group demonstrated significant improvements hour 1 to hour 4 in oxygenation (365.8 ± 53.0 vs 584.4 ± 21.0 mm Hg, p = 0.02) and dynamic compliance (9.0 ± 2.8 vs 15.0 ± 3.6, p = 0.02 mL/cm H2O).EVLP successfully rehabilitated LPS-induced lung injury in this preclinical porcine model and may thus provide a means to rehabilitate many types of acute lung injury.

SUBMITTER: Mehaffey JH

PROVIDER: S-EPMC5438908 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury.

Mehaffey J Hunter JH Charles Eric J EJ Sharma Ashish K AK Salmon Morgan M Money Dustin D Schubert Sarah S Stoler Mark H MH Tribble Curtis G CG Laubach Victor E VE Roeser Mark E ME Kron Irving L IL

The Annals of thoracic surgery 20170421 6

<h4>Background</h4>Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury.<h4>Methods</h4>We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcin ...[more]

PMID: 28434548

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Project description:OBJECTIVE:Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS:Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. RESULTS:Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. CONCLUSIONS:Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

Project description:ImportanceThe mortality rate for individuals on the wait list for lung transplant is 15% to 25%, and still only 20% of lungs from multiorgan donors are used for lung transplant. The lung donor pool may be increased by assessing and reconditioning high-risk extended criteria donor lungs with ex vivo lung perfusion (EVLP), with similar short-term outcomes.ObjectiveTo assess the long-term outcomes of transplant recipients of donor lungs treated with EVLP.Design, setting, and participantsThis retrospective cohort single-center study was conducted from August 1, 2008, to February 28, 2017, among 706 recipients of donor lungs not undergoing EVLP and 230 recipients of donor lungs undergoing EVLP.ExposureDonor lungs undergoing EVLP.Main outcomes and measuresThe incidence of chronic lung allograft dysfunction and allograft survival during the 10-year EVLP era were the primary outcome measures. Secondary outcomes included donor characteristics, maximum predicted percentage of forced expiratory volume in 1 second, acute cellular rejection, and de novo donor-specific antibody development.ResultsThis study included 706 patients (311 women and 395 men; median age, 50 years [interquartile range, 34-61 years]) in the non-EVLP group and 230 patients (85 women and 145 men; median age, 46 years [interquartile range, 32-55 years]) in the EVLP group. The EVLP group donors had a significantly lower mean (SD) Pao2:fraction of inspired oxygen ratio than the non-EVLP group donors (348 [108] vs 422 [88] mm Hg; P < .001), higher prevalence of abnormal chest radiography results (135 of 230 [58.7%] vs 349 of 706 [49.4%]; P = .02), and higher proportion of smoking history (125 of 204 [61.3%] vs 322 of 650 [49.5%]; P = .007). More recipients in the EVLP group received single-lung transplants (62 of 230 [27.0%] vs 100 of 706 [14.2%]; P < .001). There was no significant difference in time to chronic lung allograft dysfunction between the EVLP and non-EVLP group (70% vs 72% at 3 years; 56% vs 56% at 5 years; and 53% vs 36% at 9 years; log-rank P = .68) or allograft survival between the EVLP and non-EVLP groups (73% vs 72% at 3 years; 62% vs 58% at 5 years; and 50% vs 44% at 9 years; log-rank P = .97) between the 2 groups. All secondary outcomes were similar between the 2 groups.Conclusions and relevanceSince 2008, 230 of 936 lung transplants (24.6%) in the Toronto Lung Transplant Program were performed after EVLP assessment and treatment. Use of EVLP-treated lungs led to an increase in the number of patients undergoing transplantation, with comparable long-term outcomes.

Dataset Information

Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury.

Publications

Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury.

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