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External pressure dynamics promote kidney viability and perfusate filtration during ex vivo kidney perfusion.

ABSTRACT: Normothermic machine perfusion (NMP) has not yet been established as a technique for preserving organs for a day. A key contributing factor to the same is that the perfusing solutions cannot circulate continuously and evenly in the organs. Here, we conceived a method of applying intermittent air pressure from outside the organ to assist its circulatory distribution during perfusion. We used a perfusion culture system while applying external pressure to culture rat kidneys and compared the circulatory distribution in the kidneys, changes in tissue morphology due to injury, and perfusate filtration. The intermittent pressurization (IMP) (-) group showed markedly poorer circulation on the upper side compared with that in the lower side, alongside histological damage. On the other hand, the IMP (+) group showed improved circulation in the upper side and had lesser histological damage. Furthermore, the IMP (+) group maintained the ability to filter perfusate for 24 h. In transplantation medicine and regenerative medicine research, this method has the potential to contribute to more efficient organ preservation and more functional tissue regeneration in the future.

SUBMITTER: Higashi Y

PROVIDER: S-EPMC9747902 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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External pressure dynamics promote kidney viability and perfusate filtration during ex vivo kidney perfusion.

Higashi Yuhei Y Homma Jun J Sekine Hidekazu H Yago Hiroki H Kobayashi Eiji E Shimizu Tatsuya T

Scientific reports 20221213 1

Normothermic machine perfusion (NMP) has not yet been established as a technique for preserving organs for a day. A key contributing factor to the same is that the perfusing solutions cannot circulate continuously and evenly in the organs. Here, we conceived a method of applying intermittent air pressure from outside the organ to assist its circulatory distribution during perfusion. We used a perfusion culture system while applying external pressure to culture rat kidneys and compared the circul ...[more]

PMID: 36513748

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Project description:ObjectiveCritical 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.MethodsTwo 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.ResultsAirway 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.ConclusionsPressure-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.

Dataset Information

External pressure dynamics promote kidney viability and perfusate filtration during ex vivo kidney perfusion.

Publications

External pressure dynamics promote kidney viability and perfusate filtration during ex vivo kidney perfusion.

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