Composite Vascularized Allograft Machine Preservation: State of the Art

Rezaei, Majid; Figueroa, Brian; Ordenana, Carlos; Brunengraber, Henri; Dasarathy, Srinivasan; Rampazzo, Antonio; Gharb, Bahar Bassiri

doi:10.1007/s40472-019-00263-0

Cited by 7 publications

(9 citation statements)

References 95 publications

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“…13 Ex vivo normothermic perfusion (EVNP) has been used as an alternative to static cold storage (SCS) to improve allograft quality in solid organ and vascularized composite allotransplantation (VCA). 14,15 Preclinical and early clinical series seem to support an advantageous effect of oxygenation during EVNP. 16 Perfusion solutions containing packed red blood cells (pRBC) as an oxygen carrier have been shown to improve outcomes when compared with acellular perfusates.…”

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confidence: 99%

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Ex vivo normothermic preservation of amputated limbs with a hemoglobin-based oxygen carrier perfusate

Figueroa

Said

Rezaei

et al. 2021

J Trauma Acute Care Surg

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BACKGROUND: Ex vivo normothermic limb perfusion (EVNLP) preserves amputated limbs under near-physiologic conditions. Perfusates containing red blood cells (RBCs) have shown to improve outcomes during ex vivo normothermic organ perfusion, when compared with acellular perfusates. To avoid limitations associated with the use of blood-based products, we evaluated the feasibility of EVNLP using a polymerized hemoglobin-based oxygen carrier-201 (HBOC-201). METHODS:Twenty-four porcine forelimbs were procured from Yorkshire pigs. Six forelimbs underwent EVNLP with an HBOC-201-based perfusate, six with an RBC-based perfusate, and 12 served as static cold storage (SCS) controls. Ex vivo normothermic limb perfusion was terminated in the presence of systolic arterial pressure of 115 mm Hg or greater, fullness of compartments, or drop of tissue oxygen saturation by 20%. Limb contractility, weight change, compartment pressure, tissue oxygen saturation, oxygen uptake rates (OURs) were assessed. Perfusate fluid-dynamics, gases, electrolytes, metabolites, methemoglobin, creatine kinase, and myoglobin concentration were measured. Uniformity of skin perfusion was assessed with indocyanine green angiography and infrared thermography. RESULTS:Warm ischemia time before EVNLP was 35.50 ± 8.62 minutes (HBOC-201), 30.17 ± 8.03 minutes (RBC) and 37.82 ± 10.45 (SCS) ( p = 0.09). Ex vivo normothermic limb perfusion duration was 22.5 ± 1.7 hours (HBOC-201) and 28.2 ± 7.3 hours (RBC) ( p = 0.04). Vascular flow (325 ± 25 mL•min −1 vs. 444.7 ± 50.6 mL•min −1 ; p = 0.39), OUR (2.0 ± 1.45 mL O 2 •min −1 •g −1 vs. 1.3 ± 0.92 mL O 2 •min −1 •g −1

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confidence: 99%

“…Ex vivo normothermic perfusion (EVNP) has been used as an alternative to static cold storage (SCS) to improve allograft quality in solid organ and vascularized composite allotransplantation (VCA) 14,15 . Preclinical and early clinical series seem to support an advantageous effect of oxygenation during EVNP 16 .…”

mentioning

confidence: 99%

Ex vivo normothermic preservation of amputated limbs with a hemoglobin-based oxygen carrier perfusate

Figueroa

Said

Rezaei

et al. 2021

J Trauma Acute Care Surg

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“…Current experience supports that shorter ischemia duration results in superior allograft function, 34 and decreased incidence of acute and chronic rejection in limb transplantation 35 . Ex vivo normothermic perfusion (EVNP) is gaining popularity as an alternative to SCS to improve allograft preservation in solid organ and vascularized composite allotransplantation (VCA) 17 . However, ongoing metabolic activity during normothermic perfusion increases the demands of substrate supply and catabolite removal, requiring close monitoring of cellular integrity.…”

Section: Discussionmentioning

confidence: 99%

“…Gradual loss of tissue viability occurs, resulting in increased vascular resistance and compartment pressure that necessitates perfusion termination. Most groups conduct ex vivo limb perfusion experiments under subnormothermic or hypothermic conditions 14–17 . To date, there have been no studies dedicated to defining the maximum acceptable normothermic machine perfusion duration for limbs 9 .…”

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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“…Although SCS is commonly used for VCA graft preservation in clinical settings, a number of limitations exist, including: (1) extensive tissue damage after prolonged hypothermic preservation, (2) difficulty in assessing graft viability prior to transplantation, and (3) limited preservation time, wherein most VCA grafts are limited to less than 6 h of SCS. 46,98,99 These inherent limitations of SCS have encouraged research into new technologies that would allow for better graft preservation. Emerging techniques in VCA preservation can be broadly classified into two categories: (1) machine perfusion and (2) cryopreservation.…”

Section: Future Strategiesmentioning

confidence: 99%

Preservation solutions for attenuation of ischemia–reperfusion injury in vascularized composite allotransplantation

2021

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Vascularized composite allotransplantation represents the final level of the reconstructive ladder, offering treatment options for severe tissue loss and functional deficiencies. Vascularized composite allotransplantation is particularly susceptible to ischemia–reperfusion injury and requires preservation techniques when subjected to extended storage times prior to transplantation. While static cold storage functions to reduce ischemic damage and is widely employed in clinical settings, there exists no consensus on the ideal preservation solution for vascularized composite allotransplantation. This review aims to highlight current clinical and experimental advances in preservation solution development and their critical role in attenuating ischemia–reperfusion injury in the context of vascularized composite allotransplantation.

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Composite Vascularized Allograft Machine Preservation: State of the Art

Cited by 7 publications

References 95 publications

Ex vivo normothermic preservation of amputated limbs with a hemoglobin-based oxygen carrier perfusate

Ex vivo normothermic preservation of amputated limbs with a hemoglobin-based oxygen carrier perfusate

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

Preservation solutions for attenuation of ischemia–reperfusion injury in vascularized composite allotransplantation

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