J Reconstr Microsurg 2013; 29(06): 417-420
DOI: 10.1055/s-0033-1343837
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Monitorization of Asymmetric Dimethylarginine (ADMA) Levels in an Experimental Ischemia-Reperfusion Flap Model: A Preliminary Report

Onder Karaaslan
1   Izmir Ataturk Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Izmir, Turkey
,
Erhan Sonmez
1   Izmir Ataturk Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Izmir, Turkey
,
Yuksel Kankaya
2   Ankara Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Ankara, Turkey
,
Ozlem Karatas Silistreli
1   Izmir Ataturk Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Izmir, Turkey
,
Murat Melih Can
1   Izmir Ataturk Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Izmir, Turkey
,
Yagmur Kaan Bedir
1   Izmir Ataturk Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Izmir, Turkey
,
Gorkem Caliskan
1   Izmir Ataturk Training and Research Hospital, Plastic Reconstructive and Aesthetic Surgery Clinic, Izmir, Turkey
› Institutsangaben
Weitere Informationen

Publikationsverlauf

07. September 2012

31. Dezember 2012

Publikationsdatum:
12. April 2013 (online)

Abstract

One of the most important endothelium-derived vasoactive mediators is nitric oxide (NO). Endothelial dysfunction by the loss of NO is a critical event during ischemia. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NO synthase (NOS) that inhibits vascular endothelial NO production in concentrations found in pathophysiological conditions. The goal of this study was to monitorize overexpression of ADMA in an experimental ischemia-reperfusion flap model. This study was performed using 20 rats. The baseline ADMA levels were measured preoperatively. In Group I (n = 10, control) abdominal flaps were harvested and replaced in situ without creating ischemia. The plasma ADMA levels were measured at 1, 12, and 24 hours postoperatively. In Group II (n = 10, study) abdominal flaps were harvested, and clamping the vascular pedicle created a subsequent 8-hour period of warm ischemia. Clamps were removed and provided tissue reperfusion. The ADMA levels were taken after 1 hour of reperfusion, and at 12th and 24th hours. The mean preoperative ADMA levels in group I and group II were calculated to be 0.37 ± 0.06 (µmol/L) and 0.40 ± 0.06 (µmol/L), respectively. The differences between the preoperative ADMA levels were not statistically significant (p > 0.05). The mean postoperative ADMA levels in group I (control) were calculated to be 0.39 ± 0.09 (µmol/L) at the first hour, 0.42 ± 0.07 (µmol/L) at the 12th hour, and 0.40 ± 0.08 (µmol/L) at the 24th hour. Respectively, the mean postoperative ADMA levels in group II were calculated to be 0.68 ± 0.14 (µmol/L) after 1 hour of reperfusion, 0.62 ± 0.09 (µmol/L) at the 12th hour, and 0.60 ± 0.12 (µmol/L) at the 24th hour. All postoperative ADMA levels were significantly higher in Group II (p < 0.05). These experimental results suggest that systemic production of ADMA is greater in animals having ischemia reperfusion injury of the skin flaps. The strategy of decreasing levels of ADMA may be beneficial to prevent ischemia-reperfusion injury of flaps or composite transplants; thus, ADMA might be an important candidate of therapeutic target in flap or transplantation surgeries.

 
  • References

  • 1 Matsuoka H, Itoh S, Kimoto M , et al. Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension 1997; 29 (1 Pt 2) 242-247
  • 2 Bełtowski J, Kedra A. Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. Pharmacol Rep 2006; 58 (2) 159-178
  • 3 Böger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “L-arginine paradox” and acts as a novel cardiovascular risk factor. J Nutr 2004; 134 (10, Suppl): 2842S-2847S , discussion 2853S
  • 4 Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 2004; 24 (6) 1023-1030
  • 5 Zhang Z, Zou YY, Li FJ, Hu CP. Asymmetric dimethylarginine: a novel biomarker of gastric mucosal injury?. World J Gastroenterol 2011; 17 (17) 2178-2180
  • 6 Stühlinger MC, Conci E, Haubner BJ , et al. Asymmetric dimethyl L-arginine (ADMA) is a critical regulator of myocardial reperfusion injury. Cardiovasc Res 2007; 75 (2) 417-425
  • 7 Sousse LE, Yamamoto Y, Enkhbaatar P , et al. Acute lung injury-induced collagen deposition is associated with elevated asymmetric dimethylarginine and arginase activity. Shock 2011; 35 (3) 282-288
  • 8 Fliser D. Perspectives in renal disease progression: the endothelium as a treatment target in chronic kidney disease. J Nephrol 2010; 23 (4) 369-376
  • 9 Prada FS, Arrunategui G, Alves MC, Ferreira MC, Zumiotti AV. Effect of allopurinol, superoxide-dismutase, and hyperbaric oxygen on flap survival. Microsurgery 2002; 22 (8) 352-360
  • 10 Carroll WR, Esclamado RM. Ischemia/reperfusion injury in microvascular surgery. Head Neck 2000; 22 (7) 700-713
  • 11 Russell RC, Roth AC, Kucan JO, Zook EG. Reperfusion injury and oxygen free radicals: a review. J Reconstr Microsurg 1989; 5 (1) 79-84
  • 12 Dayoub H, Rodionov RN, Lynch C , et al. Overexpression of dimethylarginine dimethylaminohydrolase inhibits asymmetric dimethylarginine-induced endothelial dysfunction in the cerebral circulation. Stroke 2008; 39 (1) 180-184
  • 13 Shibata R, Ueda S, Yamagishi S , et al. Involvement of asymmetric dimethylarginine (ADMA) in tubulointerstitial ischaemia in the early phase of diabetic nephropathy. Nephrol Dial Transplant 2009; 24 (4) 1162-1169