-
Je něco špatně v tomto záznamu ?
Reduced Hypoxia-Related Genes in Porcine Limbs in Ex Vivo Hypothermic Perfusion Versus Cold Storage
N. Krezdorn, D. Sakthivel, M. Turk, MA. Aycart, S. Tasigiorgos, EM. Bueno, I. Sinha, B. Pomahac,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ischemia-reperfusion injury remains the major limiting factor for limb replantation and transplantation. Static cold storage (SCS) on ice currently represents the standard mode of preservation but is limited to 6 h of duration. Ex vivo machine perfusion has evolved as a potential alternative to safely extend the duration of ex vivo preservation by providing continuous supply of oxygen and nutrients. This study aims to evaluate underlying molecular mechanisms of both preservation modalities. METHODS: We assessed molecular changes in amputated porcine forelimbs stored on ice at 4°C for 2 h (n = 2) and limbs perfused with Perfadex solution at 10°C for 2 h (n = 3) or 12 h (n = 3) before replantation. Muscle biopsies were examined for histological changes and gene expression levels using H&E staining and a hypoxia-related PCR gene array, respectively. RESULTS: Histology revealed only minor differences between the ice (SCS) and perfusion groups after 2 h of preservation, with decreased muscle fiber disruption in the perfusion groups compared with the ice (SCS) group. Perfused limbs demonstrated downregulation of genes coding for glycolytic pathways and glucose transporters after 2 h and 12 h when compared with SCS after 2 h. Similarly, genes that induce angiogenesis and those that are activated on DNA damage were downregulated in both perfusion groups as compared with SCS. CONCLUSIONS: Perfusion of porcine limbs resulted in less activation of hypoxia-related gene families when compared with SCS. This may indicate a state more closely resembling physiological conditions during perfusion and potentially limiting ischemic injury. Our study confirms ex vivo perfusion for up to 12 h as a viable alternative for preservation of vascularized composite tissues.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc19000248
- 003
- CZ-PrNML
- 005
- 20210208143402.0
- 007
- ta
- 008
- 190107s2018 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.jss.2018.05.067 $2 doi
- 035 __
- $a (PubMed)30463709
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Krezdorn, Nicco $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany.
- 245 10
- $a Reduced Hypoxia-Related Genes in Porcine Limbs in Ex Vivo Hypothermic Perfusion Versus Cold Storage / $c N. Krezdorn, D. Sakthivel, M. Turk, MA. Aycart, S. Tasigiorgos, EM. Bueno, I. Sinha, B. Pomahac,
- 520 9_
- $a BACKGROUND: Ischemia-reperfusion injury remains the major limiting factor for limb replantation and transplantation. Static cold storage (SCS) on ice currently represents the standard mode of preservation but is limited to 6 h of duration. Ex vivo machine perfusion has evolved as a potential alternative to safely extend the duration of ex vivo preservation by providing continuous supply of oxygen and nutrients. This study aims to evaluate underlying molecular mechanisms of both preservation modalities. METHODS: We assessed molecular changes in amputated porcine forelimbs stored on ice at 4°C for 2 h (n = 2) and limbs perfused with Perfadex solution at 10°C for 2 h (n = 3) or 12 h (n = 3) before replantation. Muscle biopsies were examined for histological changes and gene expression levels using H&E staining and a hypoxia-related PCR gene array, respectively. RESULTS: Histology revealed only minor differences between the ice (SCS) and perfusion groups after 2 h of preservation, with decreased muscle fiber disruption in the perfusion groups compared with the ice (SCS) group. Perfused limbs demonstrated downregulation of genes coding for glycolytic pathways and glucose transporters after 2 h and 12 h when compared with SCS after 2 h. Similarly, genes that induce angiogenesis and those that are activated on DNA damage were downregulated in both perfusion groups as compared with SCS. CONCLUSIONS: Perfusion of porcine limbs resulted in less activation of hypoxia-related gene families when compared with SCS. This may indicate a state more closely resembling physiological conditions during perfusion and potentially limiting ischemic injury. Our study confirms ex vivo perfusion for up to 12 h as a viable alternative for preservation of vascularized composite tissues.
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Sakthivel, Dharaniya $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- 700 1_
- $a Turk, Marvee $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- 700 1_
- $a Aycart, Mario A $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- 700 1_
- $a Tasigiorgos, Sotirios $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- 700 1_
- $a Bueno, Ericka M $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- 700 1_
- $a Sinha, Indranil $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA.
- 700 1_
- $a Pomahač, Bohdan, $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: bpomahac@bwh.harvard.edu. $d 1971- $7 xx0117402
- 773 0_
- $w MED00002957 $t The Journal of surgical research $x 1095-8673 $g Roč. 232, č. - (2018), s. 137-145
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/30463709 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20190107 $b ABA008
- 991 __
- $a 20210208143402 $b ABA008
- 999 __
- $a ind $b bmc $g 1363805 $s 1038371
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2018 $b 232 $c - $d 137-145 $e 20180704 $i 1095-8673 $m The Journal of surgical research $n J Surg Res $x MED00002957
- LZP __
- $a Pubmed-20190107