Prolonged (≥24 Hours) Normothermic (≥32 °C) Ex Vivo Organ Perfusion: Lessons From the Literature

Tchouta, Lise; Alghanem, Fares; Rojas-Peña, Álvaro; Bartlett, Robert H.

doi:10.1097/tp.0000000000003475

Cited by 6 publications

(6 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent review of the experimental literature found only 3 reports of prolonged NEHP. 18 None provided hemodynamic assessment in the working heart mode and none reported transplantation after prolonged ex vivo preservation for assessment of cardiac function. Clinically, effective ex vivo perfusion devices have been developed for organ preservation and potential therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Twenty-four-hour Normothermic Ex Vivo Heart Perfusion With Low Flow Functional Assessment in an Adult Porcine Model

Spencer,

Wilhelm,

Urrea

et al. 2024

Transplantation

Self Cite

View full text Add to dashboard Cite

Background. Cold static storage and normothermic ex vivo heart perfusion are routinely limited to 6 h. This report describes intermittent left atrial (LA) perfusion that allows cardiac functional assessment in a working heart mode. Methods. Using our adult porcine model, general anesthesia was induced and a complete cardiectomy was performed following cardioplegic arrest. Back-table instrumentation was completed and normothermic ex vivo heart perfusion (NEHP) was initiated in a nonworking heart mode (Langendorff). After 1 h of resuscitation and recovery, LA perfusion was initiated and the heart was transitioned to a coronary flow-only working heart mode for 30 min. Baseline working heart parameters were documented and the heart was returned to nonworking mode. Working heart assessments were performed for 30 min every 6 h for 24 h. Results. Twenty-four-hour NEHP on 9 consecutive hearts (280 ± 42.1 g) was successful and no significant differences were found between working heart parameters at baseline and after 24 h of perfusion. There was no difference between initial and final measurements of LA mean pressures (5.0 ± 3.1 versus 9.0 ± 6.5 mm Hg, P = 0.22), left ventricular systolic pressures (44.3 ± 7.2 versus 39.1 ± 9.0 mm Hg, P = 0.13), mean aortic pressures (30.9 ± 5.8 versus 28.1 ± 8.1 mm Hg, P = 0.37), and coronary resistance (0.174 ± 0.046 versus 0.173 ± 0.066 mL/min/g, P = 0.90). There were also no significant differences between lactate (2.4 ± 0.5 versus 2.6 ± 0.4 mmol/L, P = 0.17) and glucose (173 ± 75 versus 156 ± 70 mg/dL, P = 0.37). Conclusions. A novel model using intermittent LA perfusion to create a coronary flow-only working heart mode for assessment of ex vivo cardiac function has been successfully developed.

show abstract

Section: Discussionmentioning

confidence: 99%

Twenty-four-hour Normothermic Ex Vivo Heart Perfusion With Low Flow Functional Assessment in an Adult Porcine Model

Spencer,

Wilhelm,

Urrea

et al. 2024

Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…6 In our literature review of NEVP, we found only 50 reports of successful perfusion for ≥24 hours, all using a perfusion circuit similar to an infant ECMO circuit. 7 There are currently three companies manufacturing devices for clinical human normothermic organ perfusion: Transmedics Organ Care System (heart, lung, liver), Organox (liver), and XVIVO perfusion system (lung). 1,[8][9][10][11] However, these systems are limited to 6 hours, after which organs begin to fail and are no longer suitable for transplantation.…”

Section: Discussionmentioning

confidence: 99%

Prolonged (24-hour) Normothermic ex vivo Heart Perfusion Facilitated by Perfusate Hemofiltration

Johnson¹,

Fallon²,

Langley³

et al. 2022

ASAIO Journal

Self Cite

View full text Add to dashboard Cite

Currently, normothermic ex vivo heart perfusion (NEVHP) is limited to 6-12 hours. NEVHP for 24 hours or more would allow organ treatment, assessment of organ function, and nearperfect recipient matching. We present a model of NEVHP using continuous hemofiltration (HFn) with sustained myocardial viability up to 24 hours. Twenty hearts from 6-10 kg piglets were procured and maintained on our NEVHP circuit. HFn hearts (n = 10) underwent NEVHP with HFn, whereas controls (n = 10) used NEVHP alone. All HFn vs. four controls were viable at 24 h (p = 0.004). At end perfusion, HFn hearts had higher left ventricular systolic pressure (51.5 ± 6.8 mm Hg, 38.3 ± 5.2 mm Hg, p = 0.05), lower coronary resistance (0.83 ± 0.11 mm Hg/mL/min, 1.18 ± 0.21mmHg/mL/min, p < 0.05), and lower serum lactate levels (2.9 ± 0.4 mmol/L, 4.1 ± 0.6 mmol/L, p < 0.0001) when compared to control hearts. HFn hearts also had less extensive myocardial damage and significantly less edema than control hearts with lower weight gain and wet-dry ratios. Using our circuit, NEVHP for 24 hours is possible with HFn and allows for preservation of myocardial function, improved tissue viability, decreased tissue edema, and less myocardial injury.

show abstract

“…With technological advances and development of more complex perfusion platforms, interest in pre-transplant preservation of kidneys in a metabolically active state has sparked, with the prospect of resuscitation, repair, rejuvenation, and perhaps even regeneration (6,7). Whereas short-term machine perfusion (≤6h) allows for resuscitation and viability assessment, extended preservation is likely needed for reconditioning, repair and regeneration of the graft (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…Ex vivo preservation of human livers has been prolonged to 7-days (11), with promising 1-year post transplant outcomes for a patient that received a liver graft after 3-days of ex vivo preservation (7,9,12). In contrast to the advances seen in multi-day preservation of human livers (6,8,(11)(12)(13), preservation of donor kidneys in a metabolically active state seems far more challenging.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Advancing multi-day ex vivo kidney perfusion using spatially resolved metabolomics

Haan

Witjas

Graaf

et al. 2023

Preprint

View full text Add to dashboard Cite

The ability to preserve metabolically active kidneys ex vivo for multiple days may permit reconditioning, repair and regeneration of deceased donor kidneys. However, the kidneys high metabolic demand limits its functional preservation. Current approaches focus on normothermic machine perfusion (NMP) at 37C or hypothermic machine perfusion (HMP) at 4-8C. At normothermia, kidneys are metabolically active but ex vivo preservation is limited to hours. During hypothermia kidneys can be preserved up to 24 hours but are metabolically inactive and suffer cold-induced injury. Therefore, we revisited sub normothermic perfusion (at 25C) as an alternative approach to preserve human kidneys in a metabolically active state for extended periods of time. In a custom-made platform that includes a cell-free perfusate enriched with TCA cycle fuels, urine recirculation, and continuous hemofiltration we perfused discarded human kidneys up to 8 days. Using spatially resolved single cell resolution isotope tracing we demonstrate active metabolism in all the different renal cell types over this period. However, beyond 4 days cell composition of nephron segments assessed with spatial lipidomics changed substantially and injury markers such as NGAL and LDH increased in the perfusate. Up to 4 days, perfused human discarded donor kidneys maintained metabolic fluxes, functional parameters and allow for reperfusion using a porcine auto transplantation model. These data underpin that extended multi-day metabolic preservation of human kidneys is achievable using a sub normothermic perfusion platform.

show abstract

Prolonged (≥24 Hours) Normothermic (≥32 °C) Ex Vivo Organ Perfusion: Lessons From the Literature

Cited by 6 publications

References 114 publications

Twenty-four-hour Normothermic Ex Vivo Heart Perfusion With Low Flow Functional Assessment in an Adult Porcine Model

Twenty-four-hour Normothermic Ex Vivo Heart Perfusion With Low Flow Functional Assessment in an Adult Porcine Model

Prolonged (24-hour) Normothermic ex vivo Heart Perfusion Facilitated by Perfusate Hemofiltration

Advancing multi-day ex vivo kidney perfusion using spatially resolved metabolomics

Contact Info

Product

Resources

About