title: Drug mixture which improves survival of ischemic rabbit epigastric skin flaps.
abstract: The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl2 (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes.
authors.affiliation: Microsurgery Research Centre, St. Vincent's Hospital, Melbourne, Victoria, Australia.
authors.forename: D A
authors.initials: DA
authors.lastname: Lepore
authors.forename: K R
authors.initials: KR
authors.lastname: Knight
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: M
authors.initials: M
authors.lastname: Ritz
authors.forename: S P
authors.initials: SP
authors.lastname: Robbins
authors.forename: P
authors.initials: P
authors.lastname: Sieg
authors.forename: W A
authors.initials: WA
authors.lastname: Morrison
authors.forename: B M
authors.initials: BM
authors.lastname: O'Brien
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage; D000818:Animals; D003676:Deferoxamine / Q000008:administration & dosage; D003911:Dextrans / Q000008:administration & dosage; D004338:Drug Combinations; D011464:Epoprostenol / Q000008:administration & dosage; D006493:Heparin / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial; D009568:Nitrendipine / Q000008:administration & dosage; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy*; D013300:Streptokinase / Q000008:administration & dosage; D013524:Surgical Flaps; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D003911:Dextrans; D004338:Drug Combinations; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D006493:Heparin; D009568:Nitrendipine; D011464:Epoprostenol; D013300:Streptokinase; D014568:Urokinase-Type Plasminogen Activator; D003676:Deferoxamine