#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Ischemia and reperfusion injury in superficial inferior epigastric artery-based vascularized lymph node flaps


Autoři: David P. Perrault aff001;  Gene K. Lee aff001;  Antoun Bouz aff001;  Cynthia Sung aff001;  Roy Yu aff001;  Austin J. Pourmoussa aff001;  Sun Young Park aff001;  Gene H. Kim aff002;  Wan Jiao aff001;  Ketan M. Patel aff001;  Young-Kwon Hong aff001;  Alex K. Wong aff001
Působiště autorů: Division of Plastic and Reconstructive Surgery and Department of Surgery, Keck School of Medicine of USC, Los Angeles, California, United States of America aff001;  Departments of Pathology and Dermatology, Keck School of Medicine of USC, Los Angeles, California, United States of America aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227599

Souhrn

Vascularized lymph node transfer (VLNT) is a promising treatment modality for lymphedema; however, how lymphatic tissue responds to ischemia has not been well defined. This study investigates the cellular changes that occur in lymph nodes in response to ischemia and reperfusion. Lymph node containing superficial epigastric artery-based groin flaps were isolated in Prox-1 EGFP rats which permits real time identification of lymphatic tissue by green fluorescence during flap dissection. Flaps were subjected to ischemia for either 1, 2, 4, or 8 hours, by temporarily occluding the vascular pedicle. Flaps were harvested after 0 hours, 24 hours, or 5 days of reperfusion. Using EGFP signal guidance, lymph nodes were isolated from the flaps and tissue morphology, cell apoptosis, and inflammatory cytokines were quantified and analyzed via histology, immunostaining, and rtPCR. There was a significant increase in collagen deposition and tissue fibrosis in lymph nodes after 4 and 8 hours of ischemia compared to 1 and 2 hours, as assessed by picrosirius red staining. Cell apoptosis significantly increased after 4 hours of ischemia in all harvest times. In tissue subject to 4 hours of ischemia, longer reperfusion periods were associated with increased rates of CD3+ and CD45+ cell apoptosis. rtPCR analysis demonstrated significantly increased expression of CXCL1/GRO-α with 2 hours of ischemia and increased PECAM-1 and TNF-α expression with 1 hour of ischemia. Significant cell death and changes in tissue morphology do not occur until after 4 hours of ischemia; however, analysis of inflammatory biomarkers suggests that ischemia reperfusion injury can occur with as little as 2 hours of ischemia.

Klíčová slova:

Apoptosis – Collagens – Fibrosis – Gene expression – Ischemia – Lymph nodes – Reperfusion – Reperfusion injury


Zdroje

1. Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg. 2007;59(4):464–72. doi: 10.1097/01.sap.0000257149.42922.7e 17901744

2. Cormier JN, Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM. Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer. 2010;116(22):5138–49. doi: 10.1002/cncr.25458 20665892

3. Hinrichs CS, Watroba NL, Rezaishiraz H, Giese W, Hurd T, Fassl KA, et al. Lymphedema secondary to postmastectomy radiation: incidence and risk factors. Ann Surg Oncol. 2004;11(6):573–80. doi: 10.1245/ASO.2004.04.017 15172932

4. Petrek JA, Senie RT, Peters M, Rosen PP. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer. 2001;92(6):1368–77. doi: 10.1002/1097-0142(20010915)92:6<1368::aid-cncr1459>3.0.co;2-9 11745212

5. Akita S, Mitsukawa N, Kuriyama M, Kubota Y, Hasegawa M, Tokumoto H, et al. Comparison of vascularized supraclavicular lymph node transfer and lymphaticovenular anastomosis for advanced stage lower extremity lymphedema. Ann Plast Surg. 2015;74(5):573–9. doi: 10.1097/SAP.0000000000000513 25875724

6. Allen RJ Jr., Cheng MH. Lymphedema surgery: Patient selection and an overview of surgical techniques. J Surg Oncol. 2016;113(8):923–31. doi: 10.1002/jso.24170 26846615

7. Basta MN, Gao LL, Wu LC. Operative treatment of peripheral lymphedema: a systematic meta-analysis of the efficacy and safety of lymphovenous microsurgery and tissue transplantation. Plast Reconstr Surg. 2014;133(4):905–13. doi: 10.1097/PRS.0000000000000010 24352208

8. Cheng MH, Huang JJ, Wu CW, Yang CY, Lin CY, Henry SL, et al. The mechanism of vascularized lymph node transfer for lymphedema: natural lymphaticovenous drainage. Plast Reconstr Surg. 2014;133(2):192e–8e. doi: 10.1097/01.prs.0000437257.78327.5b 24469190

9. De Brucker B, Zeltzer A, Seidenstuecker K, Hendrickx B, Adriaenssens N, Hamdi M. Breast Cancer-Related Lymphedema: Quality of Life after Lymph Node Transfer. Plast Reconstr Surg. 2016;137(6):1673–80. doi: 10.1097/PRS.0000000000002169 27219223

10. Dionyssiou D, Demiri E, Tsimponis A, Sarafis A, Mpalaris V, Tatsidou G, et al. A randomized control study of treating secondary stage II breast cancer- related lymphoedema with free lymph node transfer. Breast cancer research and treatment. 2016;156(1):73–9. doi: 10.1007/s10549-016-3716-0 26895326

11. Ozturk CN, Ozturk C, Glasgow M, Platek M, Ashary Z, Kuhn J, et al. Free vascularized lymph node transfer for treatment of lymphedema: A systematic evidence based review. J Plast Reconstr Aesthet Surg. 2016;69(9):1234–47. doi: 10.1016/j.bjps.2016.06.022 27425000

12. Patel KM, Lin CY, Cheng MH. A Prospective Evaluation of Lymphedema-Specific Quality-of-Life Outcomes Following Vascularized Lymph Node Transfer. Ann Surg Oncol. 2015;22(7):2424–30. doi: 10.1245/s10434-014-4276-3 25515196

13. Tobbia D, Semple J, Baker A, Dumont D, Johnston M. Experimental assessment of autologous lymph node transplantation as treatment of postsurgical lymphedema. Plast Reconstr Surg. 2009;124(3):777–86. doi: 10.1097/PRS.0b013e3181b03787 19730296

14. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. International review of cell and molecular biology. 2012;298:229–317. doi: 10.1016/B978-0-12-394309-5.00006-7 22878108

15. Kerrigan CL, Daniel RK. Critical ischemia time and the failing skin flap. Plast Reconstr Surg. 1982;69(6):986–9. doi: 10.1097/00006534-198206000-00014 7079406

16. Siemionow M, Arslan E. Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery. 2004;24(6):468–75. doi: 10.1002/micr.20060 15378577

17. Eefting F, Rensing B, Wigman J, Pannekoek WJ, Liu WM, Cramer MJ, et al. Role of apoptosis in reperfusion injury. Cardiovasc Res. 2004;61(3):414–26. doi: 10.1016/j.cardiores.2003.12.023 14962473

18. Eckert P, Schnackerz K. Ischemic tolerance of human skeletal muscle. Ann Plast Surg. 1991;26(1):77–84. doi: 10.1097/00000637-199101000-00012 1994817

19. Zelt RG, Olding M, Kerrigan CL, Daniel RK. Primary and secondary critical ischemia times of myocutaneous flaps. Plast Reconstr Surg. 1986;78(4):498–503. doi: 10.1097/00006534-198610000-00011 3763727

20. Nguyen GK, Hwang BH, Zhang Y, Monahan JF, Davis GB, Lee YS, et al. Novel biomarkers of arterial and venous ischemia in microvascular flaps. PloS one. 2013;8(8):e71628. doi: 10.1371/journal.pone.0071628 23977093

21. Yang CY, Ho OA, Cheng MH, Hsiao HY. Critical Ischemia Time, Perfusion, and Drainage Function of Vascularized Lymph Nodes. Plast Reconstr Surg. 2018;142(3):688–97. doi: 10.1097/PRS.0000000000004673 29927833

22. Tinhofer IE, Yang CY, Chen C, Cheng MH. Impacts of arterial ischemia or venous occlusion on vascularized groin lymph nodes in a rat model. J Surg Oncol. 2019.

23. Jung E, Gardner D, Choi D, Park E, Jin Seong Y, Yang S, et al. Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm's Canal Reporter Rat. Scientific reports. 2017;7(1):5577. doi: 10.1038/s41598-017-06031-3 28717161

24. Shesol BF, Nakashima R, Alavi A, Hamilton RW. Successful lymph node transplantation in rats, with restoration of lymphatic function. Plast Reconstr Surg. 1979;63(6):817–23. 441196

25. Benahmed F, Ely S, Lu TT. Lymph node vascular-stromal growth and function as a potential target for controlling immunity. Clin Immunol. 2012;144(2):109–16. doi: 10.1016/j.clim.2012.05.004 22717771

26. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, et al. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke. 1997;28(6):1233–44. doi: 10.1161/01.str.28.6.1233 9183357

27. Bokhari FA, Shakoori TA, Butt A, Ghafoor F. TNF-alpha: a risk factor for ischemic stroke. Journal of Ayub Medical College, Abbottabad: JAMC. 2014;26(2):111–4. 25603656

28. Gurevitch J, Frolkis I, Yuhas Y, Paz Y, Matsa M, Mohr R, et al. Tumor necrosis factor-alpha is released from the isolated heart undergoing ischemia and reperfusion. Journal of the American College of Cardiology. 1996;28(1):247–52. doi: 10.1016/0735-1097(96)00105-2 8752821

29. Losy J, Zaremba J, Skrobanski P. CXCL1 (GRO-alpha) chemokine in acute ischaemic stroke patients. Folia Neuropathol. 2005;43(2):97–102. 16012911

30. Maddahi A, Kruse LS, Chen QW, Edvinsson L. The role of tumor necrosis factor-alpha and TNF-alpha receptors in cerebral arteries following cerebral ischemia in rat. Journal of neuroinflammation. 2011;8:107. doi: 10.1186/1742-2094-8-107 21871121

31. Nourshargh S, Krombach F, Dejana E. The role of JAM-A and PECAM-1 in modulating leukocyte infiltration in inflamed and ischemic tissues. Journal of leukocyte biology. 2006;80(4):714–8. doi: 10.1189/jlb.1105645 16857733

32. Turegun M, Gudemez E, Newman P, Zins J, Siemionow M. Blockade of platelet endothelial cell adhesion molecule-1 (PECAM-1) protects against ischemia-reperfusion injury in muscle flaps at microcirculatory level. Plast Reconstr Surg. 1999;104(4):1033–40. doi: 10.1097/00006534-199909020-00021 10654744

33. Wang H, Yan Z, Qiu L, Hu Z, Qian W, Xu L. Dynamic changes of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) on pulmonary injury induced by ischemia-reperfusion in rats. Irish journal of medical science. 2011;180(2):483–8. doi: 10.1007/s11845-010-0644-6 21104336

34. Knight RJ, Dikman S, Liu H, Martinelli GP. Cold ischemic injury accelerates the progression to chronic rejection in a rat cardiac allograft model. Transplantation. 1997;64(8):1102–7. doi: 10.1097/00007890-199710270-00003 9355823

35. Scaglioni MF, Arvanitakis M, Chen YC, Giovanoli P, Chia-Shen Yang J, Chang EI. Comprehensive review of vascularized lymph node transfers for lymphedema: Outcomes and complications. Microsurgery. 2018;38(2):222–9. doi: 10.1002/micr.30079 27270748


Článek vyšel v časopise

PLOS One


2020 Číslo 1
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#