Hypothermic Ex Situ Perfusion of Human Limbs With Acellular Solution for 24 Hours

Abstract

Background. Machine perfusion (MP) has evolved as a promising approach for the ex situ preservation in organ transplantation. However, the literature on the use of MP in human vascularized composite allografts is scarce. The aim of this study was to evaluate the effects of hypothermic MP with an acellular perfusate in human upper extremities and compare with the current gold standard of static cold storage (SCS). Methods. Six upper extremities were assigned to either MP (n = 3) or SCS (n = 3) conditions for 24 h. MP-extremities were perfused with oxygenated Steen solution at a constant pressure of 30 mm Hg and 10°C. Results. Median total ischemia time was 213 min (range, 127–222 min). Myoglobin, creatine-kinase (CK) showed increased levels at the start of MP (medians: myoglobin: 4377 ng/mL, CK: 1442 U/L), peaking 6 h after perfusate exchange (medians: myoglobin: 9206 ng/mL, CK: 3995 U/L) at timepoint 24. Lactate levels decreased from a median of 6.9–2.8 mmol/L over time. Expression of hypoxia-inducible factor 1-alpha peaked in the SCS-group after 8 h, followed by a decrease. Increased hypoxia-inducible factor 1-alpha expression in the MP group was delayed until 20 h. Perfusion pressure, temperature, and circuit flow were maintained at median of 30.88 mm Hg, 9.77°C, and 31.13 mL/min, respectively. Weight increased 1.4% in the SCS group and 4.3% in the MP group over 24 h. Conclusions. Hypothermic ex situ perfusion with an oxygenated acellular Steen solution may extend the allowable extracorporeal preservation time by a factor of 4–6 compared to SCS and holds promise to be beneficial for vascularized composite allograft recipients and victims of traumatic major limb amputation.

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

“…The same group subsequently reported a 10% weight gain and successful heterotopic replantation; however, they did not detail the changes that were introduced to control the weight gain 28 . Haug et al 39 perfused three human limbs, for 24 hours, with an oxygenated acellular solution with very low flow and pressure (30.4 mL·min −1 , 30 mm Hg) at 10°C. They reported 4.3% weight increase, median potassium levels of 5.7 mmol·L −1 and, lactic acid of 2.8 mmol·L −1 .…”

Some Like It Hot—A Commentary to Ex Vivo Normothermic Perfusion of Human Upper Limbs

“…Ex situ machine perfusion (EMP) has been proven to be a viable method to enhance the allowable time until transplantation, exceeding static cold storage. 1 The next requisite step to advance this technology in the niche of clinical VCA is to optimize the EMP settings as a preparation for the clinical use.…”

“…Potential assessments for the effects of IRI could be of histomorphometric or immunohistological nature. 1,8 We believe that EMP offers the possibility to assess the quality of the VCA before transplantation similar to the metabolic assessment in cardiac allograft perfusion. 9…”

Donor and Recipient Matching in Facial Vascularized Composite Allotransplantation: A Closer Look at the Donor Pool

“…To increase the geographic radius of potential vascularized composite allotransplant donors and to diminish longer ischemia time, new strategies for ex situ tissue preservation are paramount, and this donor pool may be of relevance in the future. 26 Expanding the donor pool with organs from donors that test positive for treatable viruses is a known approach in solid organ transplantation and may be of interest in vascularized composite allotransplantation. 27 A significant portion of all organ donors is hepatitis C-positive because of the increase in intravenous drug use and brain death caused by overdose.…”