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Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine.

ABSTRACT: OBJECTIVES:Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine. METHODS:A swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorporeal lungs and recipient swine. Lungs were ventilated and perfused in a normothermic chamber for 4 days. Longitudinal analyses of extracorporeal lungs (ie, functional assessments, multiscale imaging, cytokine quantification, and cellular assays) and recipient swine (eg, vital signs and blood and tissue analyses) were performed. RESULTS:Throughout 4 days of normothermic support, extracorporeal lung function was maintained (arterial oxygen tension/inspired oxygen fraction >400 mm Hg; compliance >20 mL/cm H2O), and recipient swine were hemodynamically stable (lactate <3 mmol/L; pH, 7.42 ± 0.05). Radiography revealed well-aerated lower lobes and consolidation in upper lobes of extracorporeal lungs, and bronchoscopy showed healthy airways without edema or secretions. In bronchoalveolar lavage fluid, granulocyte-macrophage colony-stimulating factor, interleukin (IL) 4, IL-6, and IL-10 levels increased less than 6-fold, whereas interferon gamma, IL-1?, IL-1?, IL-1ra, IL-2, IL-8, IL-12, IL-18, and tumor necrosis factor alpha levels decreased from baseline to day 4. Histologic evaluations confirmed an intact blood-gas barrier and outstanding preservation of airway and alveolar architecture. Cellular viability and metabolism in extracorporeal lungs were confirmed after 4 days. CONCLUSIONS:We demonstrate feasibility of normothermic maintenance of extracorporeal lungs for 4 days by cross-circulation with conscious swine. Cross-circulation approaches could support the recovery of damaged lungs and enable organ bioengineering to improve transplant outcomes.

SUBMITTER: Hozain AE

PROVIDER: S-EPMC7094131 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine.

Hozain Ahmed E AE Tipograf Yuliya Y Pinezich Meghan R MR Cunningham Katherine M KM Donocoff Rachel R Queen Dawn D Fung Kenmond K Marboe Charles C CC Guenthart Brandon A BA O'Neill John D JD Vunjak-Novakovic Gordana G Bacchetta Matthew M

The Journal of thoracic and cardiovascular surgery 20191017 4

<h4>Objectives</h4>Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine.<h4>Methods</h4>A swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorpore ...[more]

PMID: 31761338

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Project description:ObjectivesMinimally invasive extracorporeal circulation (MiECC) is suggested to have favourable impact on blood loss compared to conventional extracorporeal circulation. We aimed to compare the impact of both systems on coagulation.MethodsRandomized trial comparing endogenous thrombin-generating potential early after elective coronary surgery employing either MiECC group (n = 30) or conventional extracorporeal circulation group (n = 30). Secondary outcomes were in vivo thrombin generation, bleeding end points and haemodilution, as well as morbidity and mortality up to 30-day follow-up.ResultsCompared to the conventional extracorporeal circulation group, the MiECC group showed (i) a trend towards a higher early postoperative endogenous thrombin-generating potential (P = 0.06), (ii) lower intraoperative levels of thrombin-antithrombin complex and prothrombin fragment 1 + 2 (P < 0.001), (iii) less haemodilution early postoperatively as measured by haematocrit and weight gain, but without correlation to coagulation factors or bleeding end points. Moreover, half as many patients required postoperative blood transfusion in the MiECC group (17% vs 37%, P = 0.14), although postoperative blood loss did not differ between groups (P = 0.84). Thrombin-antithrombin complex levels (rs = 0.36, P = 0.005) and prothrombin fragment 1 + 2 (rs = 0.45, P < 0.001), but not early postoperative endogenous thrombin-generating potential (rs = 0.05, P = 0.72), showed significant correlation to increased transfusion requirements. The MiECC group demonstrated significantly lower levels of creatine kinase-MB, lactate dehydrogenase and free haemoglobin indicating superior myocardial protection, less tissue damage and less haemolysis, respectively. Perioperative morbidity and 30-day mortality did not differ between groups.ConclusionsConventional but not MiECC is associated with significant intraoperative thrombin generation despite full heparinization. No correlation between coagulation factors or bleeding end points with the degree of haemodilution could be ascertained.Clinicaltrials.gov identifierNCT03216720.

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Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine.

Publications

Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine.

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