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The effect of controlled carbon dioxide insufflation on the viability of ischemic random skin flaps in rats

Abstract

Background

Despite the indications of carboxitherapy in situations of ischemia and necrosis, there is still no scientific evidence to support its clinical applicability. The purpose of this study was to investigate the effect of controlled carbon dioxide insufflation on the viability of dorsal ischemic random skin flaps in rats.

Methods

A randomized, single-blind, experimental study was conducted. Thirty-six Wistar-EPM rats were randomly distributed into three groups: group 1 (control using ischemic random skin flap procedure without gas insufflation); group 2 (flap procedure with controlled carbon dioxide insufflation); and group 3 (flap procedure with controlled inert gas insufflation). In groups 2 and 3, gas was insufflated intradermally in rats for 5 s (150 ml/min) using a 0.2-mm needle inserted at a 90° angle to the skin at two points (one located 2.5 cm from the cranial base of the flap and the other 7.5 cm from the midline of the flap). This procedure was repeated for 7 consecutive days. Macroscopic analysis (necrotic area) was performed using the paper-template method proposed by Sasaki and Pang. Microscopic analysis of the vascularization process was performed using hematoxylin and eosin staining.

Results

No statistically significant differences were found for the parameter vascularization, inflammatory infiltrate, and percentage of necrotic area.

Conclusions

Controlled carbon dioxide insufflation did not have a significant impact on the viability of ischemic random skin flaps.

Level of evidence: Not ratable.

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References

  1. 1.

    Rednam CK, Wilson RL, Selvaraju V, Rishi MT, Thirunavukkarasu M, Coca-Soliz V, Lakshmanan R, Palesty JA, McFadden DW, Maulik N (2017) Increased survivability of ischemic skin flap tissue in Flk-1+/- mice by Pellino-1 intervention. Microcirculation 24(6). https://doi.org/10.1111/micc.12362

  2. 2.

    Lucas JB (2017) The physiology and biomechanics of skin flaps. Facial Plast Surg Clin North Am 25(3):303–311. https://doi.org/10.1016/j.fsc.2017.03.003

    Article  PubMed  Google Scholar 

  3. 3.

    Karimipour M, Amanzade V, Jabbari N, Farjah GH (2017) Effects of gamma-low dose irradiation on skin flap survival in rats. Phys Med 40:104–109. https://doi.org/10.1016/j.ejmp.2017.07.019

    Article  PubMed  Google Scholar 

  4. 4.

    Prado RP, Liebano RE, Hochman BS, Pinfild CE, Ferreira LM (2006) Experimental models for low level laser therapy on isquemic random skin flap in rats. Acta Cir Bras 21:258–262. https://doi.org/10.1590/s0102-86502006000400013

    Article  PubMed  Google Scholar 

  5. 5.

    Pinfild CE, Liebano RE, Hochman BS, Ferreira LM (2005) Hellim-neon laser in viability of randon skin flap in rats. Lasers Surg Med 37:74–77. https://doi.org/10.1002/lsm.20190

    Article  Google Scholar 

  6. 6.

    Nishioka MA (2012) Pinfild CE, Sheliga, TR, Arias VE, Gemes, HC, Ferreira LM: Led (660nm) and laser (670nm)use on skin flap viability: angiogenesis and mast cells on transition line. Lasers Med Sci 27:45–50. https://doi.org/10.1007/s10103-011-1042-7

    Article  Google Scholar 

  7. 7.

    Kerrigan CL (1983) Skin flap failure: pathophysiology. Plast Reconstr Surg 72(6):766–777. https://doi.org/10.1097/00006534-198312000-00003

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Kailiang Z, Yihui Z, Dingsheng L, Xianyao T (2016) Effects of muscone on random skin flap survival in rats. J Reconstr Microsurg 32(3):200–207. https://doi.org/10.1055/s-0035-1565264

    Article  PubMed  Google Scholar 

  9. 9.

    Junior IE, Masson IB, Ferreira LM, Liebano RE, Baldan C, Gomes AC (2005) Administração tópica de cloridrato de hidralazina na viabilidade de retalho cutâneo randômico em ratos [Topical administration of hydralazine hydrochloride on the viability of randon skin flaps in rats]. Acta Cir Bras. 20(2):164–7. https://doi.org/10.1590/s0102-86502005000200011 (Portuguese)

    Article  PubMed  Google Scholar 

  10. 10.

    Barthe GP, Suarez NC, Ortega JMR (1991) Morphological changes in the vascularisation of delayed flaps in rabbits. Br J Plast Surg 4(4):285–290. https://doi.org/10.1016/0007-1226(91)90073-s

    Article  Google Scholar 

  11. 11.

    Duarte IS, Gomes HFC, Ferreira LM (1998) Effect of dimethyl sulphoxide on necrosis of skin flaps in rats. Can J Plast Surg 6(2):93–97. https://doi.org/10.1177/229255039800600205

    Article  Google Scholar 

  12. 12

    Liebano RE, Ferreira LM, Sabino M (2003) Experimental model for transcutaneous electrical nerve stimulation on ischemic random skin flap in rats. Acta Cir Bras 18:54–59. https://doi.org/10.1590/S0102-86502003001100008

    Article  Google Scholar 

  13. 13.

    Harder Y, Amon M, Erni D, Menger MD (2004) Evolution of ischemic tissue injury in a random pattern flap: a new mouse model using intravital microscopy. J Surg Res 121(2):197–205. https://doi.org/10.1016/j.jss.2004.03.026

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Abla LE, Gomes HC, Percario S, Ferreira LM (2005) Acetylcysteine in random skin flap in rats. Acta Cir Bras 20(2):121–123. https://doi.org/10.1590/s0102-86502005000200004

    Article  PubMed  Google Scholar 

  15. 15.

    Doghaim NN, El-Tatawy RA, Neinaa YME, Abd El-Samd MM (2018) Study of the efficacy of carboxytherapy in alopecia. J Cosmet Dermatol 17(6):1275–1285. https://doi.org/10.1111/jocd.12501

    Article  PubMed  Google Scholar 

  16. 16

    Pianez LR, Custódio FS, Guidi RM, Nunes de Freitas J, Sant’Ana E (2016) Effectiveness of carboxytherapy in the treatment of cellulite in healthy women: a pilot study. Clin Cosmet Investig Dermatol 9:183–90. https://doi.org/10.2147/CCID.S102503

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17

    Brandi C, D’Anielo C, Grimaldi L, Bosi B, Dei I, Lattarulo P, Alessandrini C (2001) Carbon dioxide theraphy in the treatment of localized adiposities: clinical study and histopathological correlations. Aesthetic Plast Surg 25:170–74. https://doi.org/10.1007/s002660010116

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Toriyama T, Kumada Y, Matsubara T, Murata A, Ogino A, Hayashi H, Nakashima H, Takahashi H, Matsuo H, Kawahara H (2002) Efeito do dióxido de carbono em pacientes portadores de arteriopatia periférica com isquemia crítica. Int Angiol 21(4):367–373

    CAS  PubMed  Google Scholar 

  19. 19

    Bunyatyan ND, Drogovoz SM, Kononenko AV, Prokofiev AB (2018) Karboksiterapiia - odno iz innovatsionnykh napravleniĭ v kurortologii [Carboxytherapy - an innovative trend in resort medicine]. Vopr Kurortol Fizioter Lech Fiz Kult. 95(5):72–76. https://doi.org/10.17116/kurort20189505172 (Russian)

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Ferreira JC, Haddad A, Tavares SA (2008) Increase in collagen turnover induced by intradermal injection of carbon dioxide in rats. J Drugs Dermatol 7(3):201–206

    PubMed  Google Scholar 

  21. 21.

    Ferreira LM, Silva EK, Jaimovich CA, Calazans D, Silva ER, Furtado FA, Cosac O, Nader P, Corrêa WEMY (2012) Carboxiterapia: buscando evidência para aplicação em cirurgia plástica e dermatologia. Rev Bras Cir Plástica 27:350–351. https://doi.org/10.1590/S1983-51752012000300002

    Article  Google Scholar 

  22. 22.

    Somez A, Yaman M, Yalcin O, Ersoy B, Serin M, Sav A (2009) Carbon dioxide therapy increases capillary formation on random pedicle skin flaps in the rat. J Plast Surg 62:236–37. https://doi.org/10.1016/j.bjps.2009.01.067

    Article  Google Scholar 

  23. 23.

    Sasaki GH, Pang CY (1980) Hemodynamics and viability of acute neurovascular island skin flaps in rats. Plast Reconstr Surg 65:152–158. https://doi.org/10.1097/00006534-198002000-00005

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Korlof B, Ugland O (1966) Flaps and flap necrosis Improving the circulation in skin flaps with Complamin and with Dicoumarol: animal experiments. Acta Chir Scand 131(5):408–412

    CAS  PubMed  Google Scholar 

  25. 25.

    Qiu D, Wang X, Wang X, Jiao Y, Li Y, Jiang D (2019) Risk factors for necrosis of skin flap like wounds after ED debridement and suture. Am J Emerg Med 37(5):828–831. https://doi.org/10.1016/j.ajem.2018.07.049

    Article  PubMed  Google Scholar 

  26. 26.

    Estevão LR, Medeiros JP, Baratella-Evêncio L, Simões RS, MendonçaFde S, Evêncio-Neto J (2013) Effects of the topical administration of copaiba oil ointment (Copaifera langsdorffii) in skin flaps viability of rats. Acta Cir Bras 28(12):863–869. https://doi.org/10.1590/s0102-86502013001200009

    Article  PubMed  Google Scholar 

  27. 27.

    Peng-Fu Xu, Fang M-J, Jin Y-Z et al (2017) Effect of oxytocin on the survival of random skin flaps. Oncotarget 8(54):92955–92965. https://doi.org/10.18632/oncotarget.21696

    Article  Google Scholar 

  28. 28.

    Cury V, Bossini PS, Fangel R, Crusca Jde S, Renno AC, Parizotto NA (2009) The effects of 660nm and 780nm laser irradiation on viability of random skin flap in rats. Photomed Laser Surg 27(5):27–32. https://doi.org/10.1089/pho.2008.2383

    Article  Google Scholar 

  29. 29.

    Bossini PS, Fangel R, Habenschus RM, Renno AC, Benze B, Zuanon JA, Neto CB, Parizotto NA (2009) Low-level laser therapy (670 nm) on viability of random skin flap in rats. Lasers Med Sci 24(2):209–213. https://doi.org/10.1007/s10103-008-0551-5

    Article  PubMed  Google Scholar 

  30. 30.

    Costa CS, Otoch JP, Seelander MCL, das Neves RX, Martinez CAR, Margarido NF (2011) Avaliação citométrica dos adipócitos localizados no subcutaneo da parede anterior do abdome após infiltração percutanea de CO2. Rev Col Bras Cir 38(1):15–23. https://doi.org/10.1590/S0100-69912011000100004

    Article  PubMed  Google Scholar 

  31. 31.

    Savin E, Bailliart O, Bonnin P, Bedu M, Cheynel J, Coudert J, Martineaud JP (1995) Vasomotor effects of transcutaneous CO2 in stage II peripheral occlusive arterial disease. Angiology 46(9):785–791. https://doi.org/10.1177/000331979504600904

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Lang EV, Gossler AA, Fick LJ et al (1999) Carbon dioxide angiography: effect of injection parameters on bolus configuration. J Vasc Interv Radiol 10:41–49. https://doi.org/10.1016/s1051-0443(99)70009-6

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Brandi C, Grimaldi L, Nisi G, Brafa A, Campa A, Calambro M, Campana M, D’Aniello C (2010) The role of carbon dioxide therapy in the treatment of chronic wounds. In Vivo. 24(2):223–26

    CAS  PubMed  Google Scholar 

  34. 34.

    Alam M, Sadhwani D, Geisler A, Aslam I, Makin IRS, Schlessinger DI, Disphanurat W, Pongprutthipan M, Voravutinon N, Weil A, Chen BR, West DP, Veledar E, Poon E (2018) Subcutaneous infiltration of carbon dioxide (carboxytherapy) for abdominal fat reduction: a randomized clinical trial. J Am Acad Dermatol 79(2):320–326. https://doi.org/10.1016/j.jaad.2018.04.038

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Podgórna K, Kołodziejczak A, Rotsztejn H (2018) Cutometric assessment of elasticity of skin with striae distensae following carboxytherapy. J Cosmet Dermatol 17(6):1170–1174. https://doi.org/10.1111/jocd.12465

    Article  PubMed  Google Scholar 

  36. 36.

    Penhavel MV, Nascimento VH, Durães EF, Carneiro FP, Sousa JB (2013) Effects of carbon dioxide therapy on the healing of acute skin wounds induced on the back of rats. Acta Cir Bras 28(5):334–339. https://doi.org/10.1590/s0102-86502013000500003

    Article  PubMed  Google Scholar 

  37. 37.

    Raymundo EC, Hochman B, Nishioka MA, Freitas JOG, Maximino JR, Chadi G (2014) Effects of subcutaneous carbon dioxide on calcitonin gene related peptide and substance P secretion in rat skin. Acta Cir Bras 29(4):224–230. https://doi.org/10.1590/s0102-86502014000400002

    Article  PubMed  Google Scholar 

  38. 38.

    Valaro V, Manzo G, Mugnaini F, Bisacci C, Fiorucci P, Rango P, Bisacci R (2007) Carboxitherapy: effects on microcirculation and its use in treatment of severe lymphedema: a review. Acta Phelebol 8:1–13

    Google Scholar 

  39. 39.

    Lyra MC, Leão Júnior H, Previde Neto S, Orgaes FAFS, Gonella HA (2012) Tratamento de queimaduras de carboxiterapia em modelo experimental. Rev Bras Queimaduras 11(1):2–5

    Google Scholar 

  40. 40.

    Kołodziejczak A, Podgórna K, Rotsztejn H (2018) Is carboxytherapy a good alternative method in the removal of various skin defects? Dermatol Ther 31(5):e12699. https://doi.org/10.1111/dth.12699

    Article  PubMed  Google Scholar 

  41. 41.

    Abramo AC, Teixeira TT (2011) Carboinsuflação em úlceras crônicas dos membros inferiores. Rev Bras Cirurg Plást 26(2):205–210. https://doi.org/10.1590/S1983-51752011000200005

    Article  Google Scholar 

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Funding

No funding was received for conducting this study.

Author information

Affiliations

Authors

Contributions

Mariana Merida Carrillo Negrao participated in study conception and design, data collection, analysis, and interpretation, the technical and surgical procedures, and in writing this manuscript.

Bernardo Sérgio Hochman Rzeszetkowski participated in study conception and design.

Luiz José Muaccad Gama participated in data collection, analysis, and interpretation and in the technical procedures.

José da Conceição Carvalho Júnior participated in critical revision and final approval of this manuscript.

Lydia Masako Ferreira participated in study conception and design and in the critical revision and final approval of this manuscript.

Corresponding author

Correspondence to Lydia Masako Ferreira.

Ethics declarations

Ethical approval

This study was approved by the Research Ethics Committee and the Animal Use Ethics Committee of Federal University of São Paulo under number 0359/12. All use of animals was in agreement with the policies described in the Guide for the Care and Use of Laboratory Animals.

Consent for publication

Upon submission, all authors consent to the publication of the manuscript in the European Journal of Plastic Surgery.

Informed consent

None.

Conflict of interest

Mariana Merida Carrillo Negrao, Bernardo Sérgio Hochman Rzeszetkowski, Luiz José Muaccad Gama, José da Conceição Carvalho Júnior, and Lydia Masako Ferreira declare no competing interests.

Additional information

This work is dedicated to the memory of Bernardo Sérgio Hochman Rzeszetkowski.

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Cite this article

Negrao, M.M.C., Rzeszetkowski, B.S.H., Gama, L.J.M. et al. The effect of controlled carbon dioxide insufflation on the viability of ischemic random skin flaps in rats. Eur J Plast Surg 44, 569–576 (2021). https://doi.org/10.1007/s00238-021-01851-z

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Keywords

  • Carbon dioxide
  • Insufflation
  • Skin
  • Surgical flaps
  • Rats