Enhancement of ischaemic rabbit skin flap survival with the antioxidant and free-radical scavenger N-acetylcysteine.
1. The burst of damaging oxygen free-radicals at the time of reperfusion is one of the crucial factors affecting skin flap survival after an ischaemic interval. In these experiments the efficacy of the antioxidant and free-radical scavenger N-acetylcysteine in improving the survival of ischaemic rabbit epigastric skin flaps was tested. 2. At the time of reperfusion flaps were given: (1) balanced salt solution by intravenous whole-body administration, (2) N-acetylcysteine (200 mg/kg) by intravenous whole-body administration, (3) balanced salt solution by intra-arterial infusion into the flap, (4) N-acetylcysteine (20 mg/kg) by intra-arterial infusion into the flap, or (5) N-acetylcysteine (200 mg/kg) by intra-arterial infusion into the flap. Flap survival at 1 week, and tissue levels of parameters related to free-radical production, blood levels of thromboxane B2 and peripheral resistance during reperfusion were determined. 3. Compared with controls (groups 1 and 3) which had flap survival rates (expressed as percentage surface area surviving) of 27.1% and 31.6%, respectively. N-acetylcysteine treatment in group 2 (55.2%) and group 4 (51.9%) resulted in significant (P less than 0.05) improvements in flap survival. The survival rate in group 5 (37.7%) was not significantly better than that of the controls. 4. N-Acetylcysteine significantly reduced parameters related to free-radical production in the skin flap after 30 min of reperfusion, determined as tissue levels of malonyldialdehyde and protein oxidation products. There was also a significant decrease in peripheral resistance when low-dose N-acetylcysteine (group 4) was infused intra-arterially into the flap.(ABSTRACT TRUNCATED AT 250 WORDS)
Knight
K R
KR
Microsurgery Research Centre, St Vincent's Hospital, Melbourne, Australia.
MacPhadyen
K
K
Lepore
D A
DA
Kuwata
N
N
Eadie
P A
PA
O'Brien
B M
BM
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers; D006085:Graft Survival / Q000187:drug effects*; D007511:Ischemia / Q000188:drug therapy; D008315:Malondialdehyde / Q000378:metabolism; D010659:Phenylhydrazines / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply; D013524:Surgical Flaps; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D000975:Antioxidants; D016166:Free Radical Scavengers; D010659:Phenylhydrazines; C004787:2,4-dinitrophenylhydrazine; D008315:Malondialdehyde; D013929:Thromboxane B2; D000111:Acetylcysteine