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The effects of Losartan on abdominal wall fascial healing

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Abstract

Purpose

Losartan, a commonly used angiotensin II receptor blocker (ARB) for blood pressure control, also impairs cutaneous wound healing. Our current study will analyze how Losartan affects wound healing in the muscle and fascia from both biomechanical and histological aspects.

Methods

A total of 26 Sprague–Dawley rats were separated into one control group (NS, N = 13) and one experimental group (LG, N = 13) to receive normal saline and 40 mg/kg of Losartan by way of gastric lavage, respectively. 7 days later, all animals were subjected to a 5 cm midline laparotomy. The fascia and skin were then closed with 4-0 prolene and 5-0 vicryl. 15 days postoperatively, the animals were sacrificed and the abdominal wall harvested for wound tensiometric test and histological analysis.

Results

All 26 rats survived to the time of necropsy. Tensiometry detected significantly higher wound tensile strength in the NS group (1.6 ± 0.31 N/mm) than in the LG (1.3 ± 0.28 N/mm) group (p = 0.016). Transection histology with trichrome staining demonstrated higher degree of immature fibroplasia inside the wound in the LG group than in the NS group (p = <0.0001). The LG group also had larger incisional gaps than the NG group.

Conclusion

The antihypertensive drug, Losartan, retards wound healing in the abdominal fascia and reduces wound tensile strength in our rat model. Attention should be paid to the potential effects of various medications on fascial wound healing to guarantee optimal surgical outcomes.

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References

  1. Chudnovskii NA, Desnitskaia EV (1984) Optimization of the preoperative diagnosis of herniated lumbar disks. Zh Vopr Neirokhir Im N N Burdenko 6:51–56

    PubMed  Google Scholar 

  2. Umakanthan R, Dubose R, Byrne JG et al (2010) Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump. Heart Surg Forum 13(5):E342–E344

    Article  PubMed  Google Scholar 

  3. Berlauk JF, Abrams JH, Gilmour IJ et al (1991) Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg 214(3):289–297 (discussion 298–9)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Buse GL, Bucher E, Seeberger MD et al (2009) Perioperative management of chronic medication: to withhold, continue or intensify? Ther Umsch 66(7):509–517

    Article  PubMed  Google Scholar 

  5. Kim S, Iwao H (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52(1):11–34

    CAS  PubMed  Google Scholar 

  6. Tang HT, Cheng DS, Jia YT et al (2009) Angiotensin II induces type I collagen gene expression in human dermal fibroblasts through an AP-1/TGF-beta1-dependent pathway. Biochem Biophys Res Commun 385(3):418–423

    Article  CAS  PubMed  Google Scholar 

  7. Dussaillant GR, Gonzalez H, Cespedes C et al (1996) Regression of left ventricular hypertrophy in experimental renovascular hypertension: diastolic dysfunction depends more on myocardial collagen than it does on myocardial mass. J Hypertens 14(9):1117–1123

    Article  CAS  PubMed  Google Scholar 

  8. Yahata Y, Shirakata Y, Tokumaru S et al (2006) A novel function of angiotensin II in skin wound healing. Induction of fibroblast and keratinocyte migration by angiotensin II via heparin-binding epidermal growth factor (EGF)-like growth factor-mediated EGF receptor transactivation. J Biol Chem 281(19):13209–13216

    Article  CAS  PubMed  Google Scholar 

  9. de Gusmao FM, Becker C, Carvalho MH et al (2005) Angiotensin II inhibition during myocardial ischemia-reperfusion in dogs: effects on leukocyte infiltration, nitric oxide synthase isoenzymes activity and left ventricular ejection fraction. Int J Cardiol 100(3):363–370

    Article  PubMed  Google Scholar 

  10. Arteel GE (2004) “HOPE” for the liver? Mechanistic insight into the role of the renin-angiotensin system in hepatic fibrosis. Hepatology 40(1):263–265

    Article  CAS  PubMed  Google Scholar 

  11. Guo L, Richardson KS, Tucker LM et al (2004) Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats. Hepatology 40(3):583–589

    Article  CAS  PubMed  Google Scholar 

  12. Chen S, Zhou H, Wang L et al (2002) The effect of losartan intervention on the regulation of pulmonary arterial collagen expression by protein kinase C in chronic hypoxic rat models. Zhonghua Nei Ke Za Zhi 41(7):444–449

    CAS  PubMed  Google Scholar 

  13. Arnold SA, Rivera LB, Carbon JG et al (2012) Losartan slows pancreatic tumor progression and extends survival of SPARC-null mice by abrogating aberrant TGFbeta activation. PLoS ONE 7(2):e31384

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Viswanathan M, Saavedra JM (1992) Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing. Peptides 13(4):783–786

    Article  CAS  PubMed  Google Scholar 

  15. Ozturk CN, Tezel E, Yalcin O (2011) Evaluation of the effects of losartan on a random pattern skin flap model in rats. Ulus Travma Acil Cerrahi Derg 17(2):97–102

    Article  PubMed  Google Scholar 

  16. Biondo-Simoes Mde L, Zazula AD, Gomes AB (2006) Influence of arterial hypertension treated with losartan on skin healing in rats. Acta Cir Bras 21(3):144–150

    Article  PubMed  Google Scholar 

  17. Harth KC, Blatnik JA, Anderson JM et al (2013) Effect of surgical wound classification on biologic graft performance in complex hernia repair: an experimental study. Surgery 153(4):481–492

    Article  PubMed  Google Scholar 

  18. Franz MG (2008) The biology of hernia formation. Surg Clin North Am 88(1):1–15 vii

    Article  PubMed Central  PubMed  Google Scholar 

  19. Franz MG, Kuhn MA, Wright TE et al (2000) Use of the wound healing trajectory as an outcome determinant for acute wound healing. Wound Repair Regen 8(6):511–516

    Article  CAS  PubMed  Google Scholar 

  20. Culbertson EJ, Xing L, Wen Y et al (2011) Loss of mechanical strain impairs abdominal wall fibroblast proliferation, orientation, and collagen contraction function. Surgery 150(3):410–417

    Article  PubMed Central  PubMed  Google Scholar 

  21. Dubay DA, Franz MG (2003) Acute wound healing: the biology of acute wound failure. Surg Clin North Am 83(3):463–481

    Article  PubMed  Google Scholar 

  22. Dubay DA, Wang X, Kirk S et al (2004) Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts. Wound Repair Regen 12(5):539–545

    Article  PubMed  Google Scholar 

  23. Franz MG, Smith PD, Wachtel TL et al (2001) Fascial incisions heal faster than skin: a new model of abdominal wall repair. Surgery 129(2):203–208

    Article  CAS  PubMed  Google Scholar 

  24. Carlson MA (1997) Acute wound failure. Surg Clin North Am 77(3):607–636

    Article  CAS  PubMed  Google Scholar 

  25. Klinge U, Zheng H, Si ZY et al (1999) Synthesis of type I and III collagen, expression of fibronectin and matrix metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia. Int J Surg Investig 1(3):219–227

    CAS  PubMed  Google Scholar 

  26. Novitsky YW, Rosen MJ (2012) The biology of biologics: basic science and clinical concepts. Plast Reconstr Surg 130(5 Suppl 2):9S–17S

    Article  CAS  PubMed  Google Scholar 

  27. Yaman I, Derici H, Kara C et al (2012) Effects of resveratrol on incisional wound healing in rats. Surg Today 5:1–6

    Google Scholar 

  28. Aren A, Gökçe A, Gökçe FS (2011) Roles of matrix metalloproteinases in the etiology of inguinal hernia. Hernia 15(6):667–671

    Article  CAS  PubMed  Google Scholar 

  29. Ren M, Hao S, Yang C et al (2013) Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues. Diabetes Vasc Dis Res 10(5):426–435

    Article  Google Scholar 

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CC declares no conflict of interest.

GD declares no conflict of interest.

YG declares no conflict of interest.

JY declares no conflict of interest.

HS declares no conflict of interest.

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MR declares conflict of interest not directly related to the submitted work.

YN declares conflict of interest not directly related to the submitted work.

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Authors and Affiliations

  1. Case Comprehensive Hernia Center, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland, OH, 44106, USA

    C. N. Criss, Y. Gao, G. De Silva, J. Yang, J. M. Anderson, Y. W. Novitsky, H. Soltanian & M. J. Rosen

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  1. C. N. Criss
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  2. Y. Gao
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  3. G. De Silva
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  4. J. Yang
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  5. J. M. Anderson
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  6. Y. W. Novitsky
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  7. H. Soltanian
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  8. M. J. Rosen
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Corresponding author

Correspondence to M. J. Rosen.

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Criss, C.N., Gao, Y., De Silva, G. et al. The effects of Losartan on abdominal wall fascial healing. Hernia 19, 645–650 (2015). https://doi.org/10.1007/s10029-014-1241-9

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  • DOI: https://doi.org/10.1007/s10029-014-1241-9

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