Optimization of Ex Vivo Machine Perfusion and Transplantation of Vascularized Composite Allografts

Burlage, Laura C.; Lellouch, Alexandre G.; Taveau, Corentin B.; Tratnig-Frankl, Philipp; Pendexter, Casie A.; Randolph, Mark A.; Porte, Robert J.; Lantieri, Laurent; Tessier, Shannon N.; Cetrulo, Curtis L.; Uygun, Korkut

doi:10.1016/j.jss.2021.09.005

Cited by 16 publications

(20 citation statements)

References 79 publications

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“…Based on our previous experience with rat hindlimb perfusion [ 22 ] we considered flow rate and vascular resistance the key SNMP parameters in the forelimb model. These two parameters in the hindlimb model were critical to prevent perfusion-based injury to the grafts’ vasculature, ensuring adequate oxygenation of the tissues, and reducing edema.…”

Section: Resultsmentioning

confidence: 99%

“…We utilized our prior experience with rat hindlimb perfusion [ 22 ] as a benchmark for the forelimb perfusion parameters. Our initial control experiments in the rat forelimb began using the optimized hindlimb perfusate and perfusion metrics (21°C with the DMEM based perfusate that contained BSA (10% w/v), Dextran40 (0.5% w/v), PEG35 (0.5% w/v), Heparin (2ml/l), Insulin (200ul/l), and Dexamethasone (16mg/l)).…”

Section: Discussionmentioning

confidence: 99%

“…For machine perfusion of rat forelimbs, we adopted a hindlimb perfusion protocol our group previously developed [ 22 ]. The components and perfusate of our rat limb perfusion system are detailed in Fig 1 .…”

Section: Methodsmentioning

confidence: 99%

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Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Pendexter

Haque²,

Mojoudi³

et al. 2023

PLoS ONE

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Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Pendexter

Haque²,

Mojoudi³

et al. 2023

PLoS ONE

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“…Karangwa et al 17 . standardized nomenclature for perfusate temperature: hypothermic (0-12 °C) [18][19][20][21][22][23][24] , midthermic (13-24C°) [21][22][23][24][25][26][27] , subnormothermic (25-34 °C) 7 15,17,24-32 , and normothermic (35-38 °C) 18,30,[36][37][38][39][40][41] .…”

Section: Perfusate Temperaturementioning

confidence: 99%

Ex-Vivo Limb Perfusion

Meyers

Duarte-Bateman

Almalak

et al. 2023

EJT

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“… 18 There is no consensus on the threshold of parameters beyond which the limb is no longer considered suitable for transplantation or replantation. 13 , 18 , 19 , 20 , 21 Weight gain can be measured as a proxy for limb edema, which is a key component in the pathophysiology of compartment syndrome due to increased volume within a confined fascial space 10 , 14 , 19 , 22 , 23 , 24 Limb weight increases greater than 40% have been reported within 24 h of ex vivo limb perfusion. 25 We hypothesized that limb weight gain could be used as an early marker of skeletal muscle injury and viability during EVNLP.…”

Section: Introductionmentioning

confidence: 99%

Weight gain is an early indicator of injury in ex vivo normothermic limb perfusion (EVNLP)

et al. 2022

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Purpose There are no established criteria for discontinuing ex vivo normothermic limb perfusion (EVNLP) before irreversible damage occurs. This study evaluates weight gain as an indicator of injury during EVNLP. Methods Sixteen Yorkshire pig forelimbs were procured and preserved using EVNLP with a hemoglobin‐based oxygen carrier (HBOC‐201) or static cold storage. EVNLP continued until termination criteria were met: arterial pressure ≥ 115 mm Hg, compartment pressure > 30 mm Hg, or 20% reduction of oxygen saturation. Limb weight, contractility, hemodynamics, perfusate electrolytes, metabolites and gases were recorded. Muscles were biopsied 6‐h, and muscle injury scores (MIS) calculated. Forearm compartment pressures and indocyanine green (ICG) angiography were recorded at endpoint. Outcomes were compared at 2%, 5%, 10%, and 20% limb weight gain. Results EVNLP lasted 20 ± 3 h. Weight gain was observed after 13 ± 5 h (2%), 15 ± 6 h (5%), 16 ± 6 h (10%), and 19 ± 4 h (20%). Weight correlated positively with MIS (ρ = 0.92, p < 0.0001), potassium (ρ = −1.00, p < 0.0001), pressure (ρ = 0.78, p < 0.0001), and negatively with contractility (ρ = −0.96, p = 0.011). At 5% weight gain, MIS (p < 0.0001), potassium (p = 0.03), and lactate (p < 0.0001) were significantly higher than baseline. Median muscle contractility was 5 [3–5] at 2% weight gain, 4 [1–5] at 5%, 3 [0–4] and 2 [0–2] at 10% and 20%, respectively. At 20% weight gain, contractility was significantly lower than baseline (p = 0.003). Percent weight gain correlated negatively with endpoint ICG hoof fluorescence (r = −0.712, p = 0.047). Conclusions Weight gain correlated with microscopic muscle injury and was the earliest evidence of limb dysfunction. Weight gain may serve as a criterion for discontinuation of EVNLP.

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Optimization of Ex Vivo Machine Perfusion and Transplantation of Vascularized Composite Allografts

Cited by 16 publications

References 79 publications

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Ex-Vivo Limb Perfusion

Weight gain is an early indicator of injury in ex vivo normothermic limb perfusion (EVNLP)

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