Summary
The aim of the present study was to examine the effect of the nitric oxide synthase
(NOS) inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) on skin and flap blood flow, NOS activity and flap survival in an ischaemic
dorsal flap model in the rat.
Fifty-four rats were used in the study. l-NAME or the inactive enantiomere d-NAME was given intravenously either pre-, per- and postoperatively or only postoperatively.
Controls received saline treatment. Blood pressure and skin and flap blood flow were
monitored. NOS activity was measured in intact skin before and after l-NAME and d-NAME infusion and in flap tissue 48 h postoperatively. Forty-eight hours postoperatively flap survival was determined
in all rats.
l-NAME treatment caused: (1) a marked attenuation of constitutive Ca2+ dependent NOS activity in intact skin (p<0.001), (2) an increase in blood pressure (p<0.05), (3) a decrease in blood flow in intact skin and in skin flaps (p<0.05), and (4) a decrease in flap survival (p<0.05). In saline and d-NAME treated animals no change in blood pressure, blood flow or NOS activity in intact
skin was noted.
In conclusion this study shows that l-NAME attenuates constitutive Ca2+ dependent NOS activity in intact skin, decreases skin and flap blood flow and decreases
the survival of skin flaps. These results indicate that constitutive nitric oxide
synthase is important for basal blood flow in skin and flap tissue and for the survival
of skin flaps.
Keywords
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References
- Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil.British Journal of Surgery. 1991; 78: 651-655
- Ischemia reperfusion injury: a review.Microsurgery. 1993; 14: 165-175
- Ischemia/reperfusion injury in microvascular surgery.Head & Neck. 2000; 22: 700-713
- Review of postoperative pharmacological infusions in ischemic skin flaps.Microsurgery. 1994; 15: 675-684
- The emerging multifaceted roles of nitric oxide.Annals of Surgery. 1995; 221: 220-235
- Nitric oxide.Annals of the Rheumatic Diseases. 1996; 55: 7-20
- The yin and yang of nitric oxide: reflections on the physiology and pathophysiology of NO.Head & Neck. 2000; 22: 71-83
- Nitric oxide: its identity and role in blood pressure control.Life Sciences. 1995; 57: 1547-1556
- Nitric oxide in the regulation of blood flow and arterial pressure.Annual Review of Physiology. 1995; 57: 771-790
- The biological and pharmacological role of nitric oxide in platelet function.Advances in Experimental Medicine & Biology. 1993; 344: 251-264
- Nitric oxide: an endogenous modulator of leukocyte adhesion.Proceedings of the National Academy of Sciences of the United States of America. 1991; 88: 4651-4655
- Cytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependent, calmodulin-independent and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages.Biochemical & Biophysical Research Communications. 1991; 178: 823-829
- Inducible nitric oxide synthase in vascular smooth muscle.Arzneimittel-Forschung. 1994; 44: 432-435
- Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome.Cerebrovascular & Brain Metabolism Reviews. 1994; 6: 299-324
- Free radical chemistry of nitric oxide. Looking at the dark side.Chest. 1994; 105: 79S-84S
- The role of peroxynitrite in nitric oxide-mediated toxicity.Current Topics in Microbiology & Immunology. 1995; 196: 57-73
- Nitric oxide synthase activity and endothelial ultrastructure in ischemic skin flaps.British Journal of Plastic Surgery. 1997; 50: 483-490
- Nitric oxide synthase inhibitors improve skin flap survival in the rat.Microsurgery. 1994; 15: 708-711
- Secondary ischemic tolerance improved by administration of l-NAME in rat flaps.Microsurgery. 1996; 17: 425-427
- Involvement of nitric oxide in survival of random pattern skin flap.Plastic & Reconstructive Surgery. 1998; 101: 785-792
- Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival.British Journal of Pharmacology. 2001; 132: 1631-1638
- The protective effect of l-arginine on ischemia-reperfusion injury in rat skin flaps.Plastic & Reconstructive Surgery. 1997; 100: 1227-1233
- Pharmacological modulation of nitric oxide synthesis by mechanism-based inactivators and related inhibitors.Pharmacology & Therapeutics. 1999; 84: 157-178
- Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo.British Journal of Pharmacology. 1990; 101: 746-752
- The cutaneous circulation.in: Shepherd A.P. Öberg PÅ Laser Doppler blood flowmetry. Kluwer Academic Publishers, Norwell1990: 121-139
- The dorsal skin-flap model in the rat: factors influencing survival.Plastic & Reconstructive Surgery. 1993; 91: 316-321
- New insights into the local regulation of blood flow by perivascular nerves and endothelium.British Journal of Plastic Surgery. 1994; 47: 527-543
- Inhibitors of nitric oxide synthase in human skin.Journal of Investigative Dermatology. 1996; 106: 113-118
- Chemical biology of nitric oxide: regulation and protective and toxic mechanisms.Current Topics in Cellular Regulation. 1996; 34: 159-187
- Dexamethasone increases survival and attenuates induction of inducible nitric oxide synthase in experimental skin flaps.Ann Plast Surg. 1999; 42: 180-184
- Endotoxin alters the systemic disposition of nitric oxide synthase inhibitors in the awake sheep.Clinical & Experimental Pharmacology & Physiology. 1997; 24: 391-397
- Duration of the hemodynamic effects of N(G)-nitro-l-arginine methyl ester in vivo.Nitric Oxide. 2000; 4: 85-93
Article info
Publication history
Published online: November 24, 2006
Accepted:
July 27,
2006
Received:
July 19,
2006
Identification
Copyright
© 2006 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Inc. All rights reserved.
