Jornal Vascular Brasileiro
https://jvascbras.org/article/doi/10.1590/1677-5449.190092
Jornal Vascular Brasileiro
Original Article

Impact of topical nifedipine on wound healing in animal model (pig)

Impacto da nifedipina tópica na cicatrização de feridas em modelo animal (porco)

Augusto Cézar Lacerda Brasileiro; Dinaldo Cavalcanti de Oliveira; Pollianne Barbosa da Silva; João Kairo Soares de Lima Rocha

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Abstract

Abstract: Background: The human skin is an extremely sophisticated and evolved organ that covers the whole body. External agents or the patient’s own diseases can cause skin injuries that can challenge healthcare professionals and impose high social, economic and emotional costs.

Objectives: To evaluate the impact of topical nifedipine on skin wound healing, specifically on polymorphonuclear cells, vascular proliferation, and collagen.

Methods: We used three pigs, and created eight injuries in the dorsal region of each animal. We applied 1%, 10%, and 20% concentration nifedipine creams to four of the wounds in animals 1, 2, and 3 respectively and treated the other twelve wounds with saline solution 0.9% only. We analyzed the presence of polymorphonuclear cells, vascular proliferation, and collagen at six different times (days 1, 3, 7, 14, 21, and 28).

Results: The evaluation of polymorphonuclear levels showed mild cell activity at all times in the control group, while in the nifedipine groups, marked levels were more frequent at all times during the experiment. There was a 4.84-fold increase in the chance of marked vascular proliferation (p = 0.019) and, at the same time, a decrease in collagen formation (OR 0.02 / p = 0.005) in animal 3.

Conclusions: Topical NFD may have an impact on skin wound healing mechanisms. Our study showed that polymorphonuclear cells and vascular proliferation increased. We also demonstrated that collagen formation decreased. Therefore, topical NFD may have a positive impact on skin wound healing. Additional studies are needed to confirm our results.

Keywords

wound, topical nifedipine, polymorphonuclear cells, vascular proliferation, collagens

Resumo

Resumo: Contexto: A pele humana é um órgão extremamente sofisticado e evoluído que cobre todo o corpo. As lesões cutâneas podem ser causadas por agentes externos ou pelas próprias doenças do paciente, e podem representar um desafio para os profissionais de saúde com altos custos sociais, econômicos e emocionais.

Objetivos: Avaliar o impacto da nifedipina tópica na cicatrização de feridas cutâneas, especialmente em relação a polimorfonucleares, proliferação vascular e colágeno.

Métodos: Utilizamos três porcos e realizamos oito ferimentos na região dorsal de cada animal. Aplicamos as concentrações de nifedipina creme a 1%, 10% e 20% para os animais 1, 2 e 3, respectivamente, sendo que, em quatro ferimentos, aplicamos o creme e, nos outros quatro ferimentos, apenas soro fisiológico a 0,9%. Analisamos a presença de polimorfonucleares, proliferação vascular e colágeno em seis momentos diferentes (dias 1, 3, 7, 14, 21 e 28).

Resultados: A avaliação dos níveis polimorfonucleares mostrou atividade celular discreta em todos os momentos no grupo controle, enquanto nos grupos nifedipina, os níveis marcados foram mais frequentes em todos os momentos do experimento. Houve aumento de 4,84 vezes na chance de uma produção marcada (p = 0,019) da proliferação vascular e, ao mesmo tempo, diminuição da formação do colágeno (odds ratio, OR 0,02; p = 0,005) no animal 3.

Conclusões: A nifedipina tópica pode ter impacto no mecanismo de cicatrização cutânea. Nosso estudo mostrou que há aumento dos polimorfonucleares e da proliferação vascular. Além disso, há diminuição da formação do colágeno. Assim, a nifedipina tópica pode ter impacto positivo na cicatrização das feridas cutâneas. Estudos adicionais são necessários para confirmar nossos resultados.
 

Palavras-chave

ferida, nifedipina tópica, células polimorfonucleares, proliferação vascular, colágeno

References

1 Agale SV. Chronic leg ulcers: epidemiology, aetiopathogenesis and management. Ulcers. 2013;2013:1-9. http://dx.doi.org/10.1155/2013/413604.

2 Honsik KA, Romeo MW, Hawley CJ, Romeo SJ, Romeo JP. Sideline skin and wound care for acute injuries. Curr Sports Med Rep. 2007;6(3):147-54. PMid:19202660.

3 Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763-71. http://dx.doi.org/10.1111/j.1524-475X.2009.00543.x. PMid:19903300.

4 Leong M, Plillips LG. Cicatrização de feridas. In: Towsend CM, Beauchamp RD, Evers BM, Mattox KL. Tratado de cirurgia: a base biológica da cirurgia moderna. 19. ed. USA: Elsevier; 2015. p. 151-177.

5 Mendonça RJ, Coutinho-Netto J. Aspectos celulares da cicatrização. An Bras Dermatol. 2009;84(3):257-62. http://dx.doi.org/10.1590/S0365-05962009000300007. PMid:19668939.

6 Akhavani MA, Sivakumar B, Paleolog EM, Kang N. Angiogenesis and plastic surgery. 2008;61(12):1425-37.

7 Oigman W, Fritsch MT. Antagonistas de canais de cálcio. Hiperativo. 1998;2:104-9.

8 Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000;356(9227):366-72. http://dx.doi.org/10.1016/S0140-6736(00)02527-7. PMid:10972368.

9 Dollery C. Clinical pharmacology of calcium antagonists. Am J Hypertens. 1991;4(2 Pt 2):88S-95S. http://dx.doi.org/10.1093/ajh/4.2.88S. PMid:2021457.

10 Hafner J, Nobbe S, Partsch H, et al. Martorell hypertensive ischemic leg ulcer: a model of ischemic subcutaneous arteriolosclerosis. Arch Dermatol. 2010;146(9):961-8. http://dx.doi.org/10.1001/archdermatol.2010.224. PMid:20855694.

11 Woo TY, Wong RC, Campbell JP, Goldearb MT, Voorhees JJ, Callen JP. Nifedipine in scleroderma ulcerations. Int J Dermatol. 1984;23(10):678-80. http://dx.doi.org/10.1111/j.1365-4362.1984.tb01233.x. PMid:6526563.

12 Gasser P. Reaction of capillary blood cell velocity in nailfold capillaries to nifedipine and ketanserin in patients with vasoespastic disease. J Int Med Res. 1991;19(1):24-31. http://dx.doi.org/10.1177/030006059101900103. PMid:2019313.

13 Volk SW, Bohling MW. Comparative wound healing—are the small animal veterinarian’s clinical patients an improved translational model for human wound healing research? Wound Repair Regen. 2013;21(3):372-81. http://dx.doi.org/10.1111/wrr.12049. PMid:23627643.

14 Kim DJ, Mustoe T, Clark RA. Cutaneous wound healing in aging small mammals: a systematic review. Cutaneous wound healing in aging small mammals: a systematic review. Wound Repair Regen. 2015;23(3):318-39. http://dx.doi.org/10.1111/wrr.12290. PMid:25817246.

15 Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen. 2001;9(2):66-76. http://dx.doi.org/10.1046/j.1524-475x.2001.00066.x. PMid:11350644.

16 Hengge UR, Walker PS, Vogel JC. Expression of naked DNA in human, pig, and mouse skin. J Clin Invest. 1996;97(12):2911-6. http://dx.doi.org/10.1172/JCI118750. PMid:8675706.

17 Tfaili S, Gobinet C, Josse G, Angiboust JF, Manfait M, Piot O. Confocal Raman microspectroscopy for skin characterization: a comparative study between human skin and pig skin. Analyst (Lond). 2012;137(16):3673-82. http://dx.doi.org/10.1039/C2AN16292J. PMid:22754919.

18 Hollander DA, Erli HJ, Theisen A, Falk S, Kreck T, Müller S. Standardized qualitative evaluation of scar tissue properties in an animal wound healing model. Wound Repair Regen. 2003;11(2):150-7. http://dx.doi.org/10.1046/j.1524-475X.2003.11212.x. PMid:12631304.

19 Alsaad SMS, Ross EV, Smith WJ, DeRienzo DP. Analysis of depth of ablation, thermal damage, wound healing, and wound contraction with erbium YAG laser in a Yorkshire pig model. J Drugs Dermatol. 2015;14(11):1245-52. PMid:26580873.

20 Singer AJ, MacClain SA. Development of a porcine excisional wound model. Acad Emerg Med. 2003;10(10):1029-33. http://dx.doi.org/10.1197/S1069-6563(03)00339-7. PMid:14525733.

21 Pressley ZM, Foster JK, Kolm P, et al. Digital image analysis: a reliable tool in the quantitative evaluation of cutaneous lesions and beyond. Arch Dermatol. 2007;143(10):1331-3. http://dx.doi.org/10.1001/archderm.143.10.1331. PMid:17938354.

22 Garros IC, Campos ACL, Tâmbara EM, et al. Extrato de Passiflora edulis na cicatrização de feridas cutâneas abertas em ratos: estudo morfológico e histológico. Acta Cir Bras. 2006;21(supl 3):55-65. http://dx.doi.org/10.1590/S0102-86502006000900009.

23 Molgat YM, Pollack SV, Hurwitz JJ, et al. Comparative study of wound healing in porcine skin with CO2 laser and other surgical modalities: preliminary findings. Int J Dermatol. 1995;34(1):42-7. http://dx.doi.org/10.1111/j.1365-4362.1995.tb04379.x. PMid:7896488.

24 Miller AP, Falcone RE, Nappi J, Redmon HA. The lack of effect of nifedipine on failing skin flaps. J Dermatol Surg Oncol. 1985;11(6):612-3. http://dx.doi.org/10.1111/j.1524-4725.1985.tb01905.x. PMid:4008734.

25 Ebadi A, Cheraghali AM, Qoshoni H, Eimani H. Healing effect of topical nifedipine on skin wounds of diabetic rats. Daru. 2003;11(1):1-4.

26 Martin P, Leibovich J. Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 2005;15(11):599-607. http://dx.doi.org/10.1016/j.tcb.2005.09.002. PMid:16202600.

27 Lansdown ABG. Calcium: a potential central regulator in wound healing in the skin. Wound Repair Regen. 2002;10(5):271-85. http://dx.doi.org/10.1046/j.1524-475X.2002.10502.x. PMid:12406163.

28 Tazima MF, Vicente YA, Moriya T. Biologia da ferida e cicatrização. Medicina (B Aires). 2008;41(3):259-64.

29 Boggio RF, Boggio LF, Galvão BL, Machado-Santelli GM. Topical verapamil as a scar modulator. Aesthetic Plast Surg. 2014;38(5):968-75. http://dx.doi.org/10.1007/s00266-014-0400-9. PMid:25189298.

30 Roth M, Eickelberg O, Kohler E, Erne P, Block LH. Ca2+ channel blockers modulate metabolism of collagens within the extracellular matrix. Proc Natl Acad Sci USA. 1996;93(11):5478-82. http://dx.doi.org/10.1073/pnas.93.11.5478. PMid:8643600.

31 Smith RG. Off-label use of prescription medication: a literature review. Wounds. 2010;22(4):78-86. PMid:25901954.

32 Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412. http://dx.doi.org/10.1371/journal.pbio.1000412. PMid:20613859.
 


Submitted date:
03/31/2019

Accepted date:
11/27/2019

5eff279f0e8825db14f8e224 jvb Articles
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