Effect of Static Cold Storage on Skeletal Muscle after Vascularized Composite Tissue Allotransplantation

Gok, Emre; Kubiak, Carrie A.; Guy, Erin; Kemp, Stephen W.P.; Özer, Kağan

doi:10.1055/s-0039-1693455

Cited by 14 publications

(16 citation statements)

References 25 publications

(26 reference statements)

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“…As recently described in the literature, 6-hour SCS VCA preservation already triggers hypoxia-induced injuries to the muscle in rodent limb Txp. 35 A similar trend in post-SCS limb transplant survival was reported by Arai et al when transplanting cold stored grafts in Euro-Collins solution for 6 to 72 hours. 36 Another concern with SCS is raised by Datta et al who suggest that ischemia-reperfusion induces an inflammatory cascade leading to a systemic vascular endothelial damage.…”

Section: Discussionsupporting

confidence: 73%

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion

Goutard

Vries

Tawa

et al. 2022

J Reconstr Microsurg

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Background For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for the recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model. Methods Partial hindlimbs were procured from Lewis rats and subjected to SCS in HTK solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution or to SNMP+Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flowrate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days. Results Transplantation of limbs preserved for 0, 12, 18 and 24-hour SCS resulted in similar survival rates at post-operative day 21. Grafts cold-stored for 48 hours presented delayed graft failure (p=0.0032). SNMP of limbs after 12-hr SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hr SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hr SCS+SNMP+Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS+Txp group (p=0.01613). Conclusion To date, VCA machine perfusion is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation.

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Section: Discussionsupporting

confidence: 73%

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion

Goutard

Vries

Tawa

et al. 2022

J Reconstr Microsurg

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“…And the long-term patency rate of artificial blood vessels is poor. In contrast, vascular allografts have advantages of wide sources, easy diameter matching and well histocompatibility, becoming an ideal vein substitute material in clinic (Gok et al 2020;O'Callaghan et al 2012;Qiu et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Effects of different preservation methods of human iliac veins

et al. 2022

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With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (−186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28 days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3 days (P < 0.05), both groups were same between 3 and 14 days, and then CSG lower than FSG after 14 days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7 days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14 days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28 days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28 days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2 weeks.

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“…This study investigated the feasibility of a novel machine perfusion device for limb preservation using a pressurized closed perfusion system to improve the current standard of care compared with nonpressurized open perfusion systems. Current standard of care for limb preservation is static cold storage, which relies on the hypothermic arrest of cellular metabolism to maintain the viability of tissue 1,2 . This method was reported more than 80 years ago in the late 1930s and is still being used today because of its low cost and relative effectiveness 18 .…”

Section: Discussionmentioning

confidence: 99%

Proof of concept study for a closed ex vivo limb perfusion system for 24-hour subnormothermic preservation using acellular perfusate

Veraza

Lopez

Parry

et al. 2022

J Trauma Acute Care Surg

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BACKGROUND:The two approaches to vascularized tissue machine perfusion use either the open (nonpressurized) or closed (pressurized) perfusion system.Most studies describing isolated limb perfusion preservation rely on open perfusion systems and report tissue edema exceeding 40% after 12 to 14 hours of preservation.A variant of machine perfusion places the limb and perfusate into a reservoir closed to atmosphere. It is hypothesized that the reservoir pressure, acting as a transmural pressure, has the advantage of reducing edema formation by counteracting the hydrostatic pressure gradient from the perfusion pressure.This proof-of-concept study aim was to demonstrate feasibility of the Universal Limb Stasis System for Extended Storage (ULiSSES) device (closed, vertical perfusion system) to preserve forelimbs of Sus scrofa swine for 24 hours of subnormothermic perfusion compared with an open, horizontal perfusion system. The ULiSSES is a compact, practical device that applies pulsatile, pressurized perfusion through the novel use of a diaphragm pump powered by compressed oxygen. METHODS:Forelimbs from swine were preserved in ULiSSES device (closed perfusion system) (n = 9) and in an open perfusion system (n = 4) using subnormothermic modified Krebs-Henseleit solution. Physiological parameters were measured at the start and every 3 hours for 24 hours. Limbs were weighed before and after perfusion to compare weight gain. Edema and cellular integrity were evaluated using histopathology pre and post perfusion. RESULTS:Closed perfusion system showed superiority compared with the open perfusion system in terms of oxygen consumption, reduction in vascular resistance, and overall tissue integrity. The closed perfusion system demonstrated a 21% reduction in weight gain compared with the open perfusion system and significantly reduced intracellular edema. CONCLUSION: The ULiSSES closed, pressurized perfusion technology has translatable military applications with the potential to preserve porcine limbs for 24 hours with improved results compared with an open perfusion system.

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Effect of Static Cold Storage on Skeletal Muscle after Vascularized Composite Tissue Allotransplantation

Cited by 14 publications

References 25 publications

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion

Effects of different preservation methods of human iliac veins

Proof of concept study for a closed ex vivo limb perfusion system for 24-hour subnormothermic preservation using acellular perfusate

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