Role of NO in IR‐injury in surgical flaps For NO addition using NOS substrate, L‐arginine was supplemented in various studies either intravenously or through oral administration as an indirect donor. L‐arginine was used in a number of studies with surgical flap models in order to investigate its effects in relation to IR injury (Table 3.3). It was shown to have significant beneficial effects on flap survival after IR injury in various species.57,58,63,66‐71 Lovett et al. used microdialysis to confirm that arginine supplementation leads to increased NO production. Studies investigating the role of eNOS and iNOS inhibition have shown conflicting results of flap survival after IR injury (Table 3.3). Phan et al. used N5‐(1‐iminoethyl)‐ L‐ornithine dihydrochloride (NIO), a nonselective NOS inhibitor in an axial‐pattern flap in a rabbit IR model, and showed an increased flap survival.72 Knox et al. performed a similar study with a random‐pattern flap in a mouse and also demonstrated increased survival with NIO and a partially selective NOS inhibitor L‐NG‐nitroarginine methyl ester (L‐NAME).73 Table 3.3 Experimental results of NOS inhibition. First Author, NOS inhibitor Physiological effect Flap viability Flap Model Gribbe, 200775 L‐NAME Partially selective eNOS decreased Axial pattern cutaneous inhibition flap, rat Kuo, 20043 L‐NAME Partially selective eNOS decreased Axial pattern cutaneous inhibition flap, rat Du, 200266 L‐NAME Partially selective eNOS decreased Random pattern inhibition cutaneous flap, rat Gribbe, 19996 Dexamethasone iNOS inhibition increased Random pattern cutaneous flap, rat Guo, 199974 L‐NAME Partially selective eNOS Increased Random pattern skin inhibition flap, pig Meldrum, L‐NAME Partially selective eNOS Similar to sham Axial pattern muscle 199963 inhibition flap, rat Cordeiro, 199858 L‐NAME + partially selective eNOS decreased Myocutaneous flap, pig L‐arginine inhibition and eNOS and iNOS substrate Um, 199870 L‐NAME partially selective eNOS decreased Random pattern inhibition cutaneous flap, rat Knox, 1996 L‐NAME Partially selective eNOS Increased Random pattern inhibition cutaneous flap, rat Knox, 1994 L‐NAME Partially selective eNOS Increased Random pattern inhibition cutaneous flap, rat NIO Non selective NOS Increased inhibition iNOS inhibition Phan, 1994 NIO Non selective NOS increased Axial pattern muscle inhibition flap, rabbit Cordeiro, 199757 L‐NAME + eNOS and iNOS substrate Decreased Random pattern L‐arginine and partially selective eNOS cutaneous flap, rat inhibition 47
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