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

Abstract

Background Prolonged cold ischemia associated with static cold storage (SCS) results in higher incidence of acute and chronic allograft rejection in solid organ transplantations. Deleterious effects of SCS on vascularized composite tissue allograft were studied with limited data on muscle structure and function. The aim of this study is to evaluate the long-term impact of SCS on muscle metabolism, structure, and force generation using a syngeneic rat hindlimb transplantation model.

Methods Sixty-five male Lewis rats (250 ± 25 g) were distributed into five groups, including naive control, sciatic nerve denervation/repair, immediate transplantation, transplantation following static warm storage for 6 hours at room temperature, and transplantation following SCS for 6 hours at 4°C. Sciatic nerves were repaired in all transplantations. Muscle samples were taken for histology and metabolomics analysis following electromyography and muscle force measurements at 12 weeks after transplantation.

Results All cold-preserved limbs remained viable at 12 weeks, whereas animals receiving limbs preserved in room temperature had no survivors. The SCS transplantation group showed a 73% injury score, significantly higher than groups receiving immediate transplants without cold preservation (50%, p < 0.05). A significant decline in muscle contractile force was also demonstrated in comparison to the immediate transplantation group (p < 0.05). In the SCS group, muscle energy reserves remained relatively well preserved in surviving fibers.

Conclusion SCS extends allograft survival but fails to preserve muscle structure and force.

Keywords

static cold storage - VCA transplantation - muscle

• References

• 1 Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation 1988; 45 (04) 673-676
• 2 Taylor MJ. Biology of Cell Survival in the Cold: The Basis for Biopreservation of Tissues and Organs. Vol. 2006. Boca Raton, FL: CRC Press; 2007: 15-62
• 3 Datta N, Devaney SG, Busuttil RW, Azari K, Kupiec-Weglinski JW. Prolonged cold ischemia time results in local and remote organ dysfunction in a murine model of vascularized composite transplantation. Am J Transplant 2017; 17 (10) 2572-2579
• 4 Bonastre J, Landín L, Bolado P, Casado-Sánchez C, López-Collazo E, Díez J. Effect of cold preservation on chronic rejection in a rat hindlimb transplantation model. Plast Reconstr Surg 2016; 138 (03) 628-637
• 5 Tsuji N, Yamashita S, Sugawara Y, Kobayashi E. Effect of prolonged ischaemic time on muscular atrophy and regenerating nerve fibres in transplantation of the rat hind limb. J Plast Surg Hand Surg 2012; 46 (3–4): 217-221
• 6 Shores JT, Malek V, Lee WPA, Brandacher G. Outcomes after hand and upper extremity transplantation. J Mater Sci Mater Med 2017; 28 (05) 72
• 7 Hautz T, Engelhardt TO, Weissenbacher A. , et al. World experience after more than a decade of clinical hand transplantation: update on the Innsbruck program. Hand Clin 2011; 27 (04) 423-431 , viii
• 8 Molitor M, Kanatani T, Lanzetta M. Hind-Limb Transplantation in the Rat: Surgical Technique, Anaesthesia and Early Postoperative Management. In: Lanzetta M, Dubernard JM, Petruzzo P. , eds. Hand Transplantation. Milano: Springer Milan; 2007: 27-40
• 9 Urbanchek MG, Wei B, Egeland BM, Abidian MR, Kipke DR, Cederna PS. Microscale electrode implantation during nerve repair: effects on nerve morphology, electromyography, and recovery of muscle contractile function. Plast Reconstr Surg 2011; 128 (04) 270e-278e
• 10 Cederna PS, Youssef MK, Asato H, Urbanchek MG, Kuzon Jr WM. Skeletal muscle reinnervation by reduced axonal numbers results in whole muscle force deficits. Plast Reconstr Surg 2000; 105 (06) 2003-2009 , discussion 2010–2011
• 11 Gans C. Fiber architecture and muscle function. Exerc Sport Sci Rev 1982; 10: 160-207
• 12 Yoshimura K, Asato H, Cederna PS, Urbanchek MG, Kuzon WM. The effect of reinnervation on force production and power output in skeletal muscle. J Surg Res 1999; 81 (02) 201-208
• 13 Kung TA, Cederna PS, van der Meulen JH, Urbanchek MG, Kuzon Jr WM, Faulkner JA. Motor unit changes seen with skeletal muscle sarcopenia in oldest old rats. J Gerontol A Biol Sci Med Sci 2014; 69 (06) 657-665
• 14 McCormack MC, Kwon E, Eberlin KR. , et al. Development of reproducible histologic injury severity scores: skeletal muscle reperfusion injury. Surgery 2008; 143 (01) 126-133
• 15 Lorenz MA, Burant CF, Kennedy RT. Reducing time and increasing sensitivity in sample preparation for adherent mammalian cell metabolomics. Anal Chem 2011; 83 (09) 3406-3414
• 16 Xia J, Sinelnikov IV, Han B, Wishart DS. MetaboAnalyst 3.0–making metabolomics more meaningful. Nucleic Acids Res 2015; 43 (W1): W251-257
• 17 Atkinson DE. The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 1968; 7 (11) 4030-4034
• 18 Atkinson DE, Walton GM. Adenosine triphosphate conservation in metabolic regulation. Rat liver citrate cleavage enzyme. J Biol Chem 1967; 242 (13) 3239-3241
• 19 Landin L, Cavadas PC, Garcia-Cosmes P, Thione A, Vera-Sempere F. Perioperative ischemic injury and fibrotic degeneration of muscle in a forearm allograft: functional follow-up at 32 months post transplantation. Ann Plast Surg 2011; 66 (02) 202-209
• 20 Irwin MS. Nature and mechanism of peripheral nerve damage in an experimental model of non-freezing cold injury. Ann R Coll Surg Engl 1996; 78 (04) 372-379
• 21 van Alphen WA, Smith AR, ten Kate FJ. Maximum hypothermic ischemia in replants containing muscular tissue. J Hand Surg Am 1988; 13 (03) 415-422
• 22 Eckert P, Schnackerz K. Ischemic tolerance of human skeletal muscle. Ann Plast Surg 1991; 26 (01) 77-84
• 23 Borisov AB, Dedkov EI, Carlson BM. Interrelations of myogenic response, progressive atrophy of muscle fibers, and cell death in denervated skeletal muscle. Anat Rec 2001; 264 (02) 203-218
• 24 Dedkov EI, Kostrominova TY, Borisov AB, Carlson BM. Reparative myogenesis in long-term denervated skeletal muscles of adult rats results in a reduction of the satellite cell population. Anat Rec 2001; 263 (02) 139-154
• 25 Gok E, Ozer K. Treating the donor: strategies to prolong VCA preservation. Curr Transplant Rep 2017; 4 (04) 304-310
• 26 Suszynski TM, Wildey GM, Falde EJ. , et al. The ATP/DNA ratio is a better indicator of islet cell viability than the ADP/ATP ratio. Transplant Proc 2008; 40 (02) 346-350