Objective: Despite continued improvements in surgical technique and post- operative management of pedicled flaps, partial flap necrosis continues to be a substantial problem in plastic and reconstructive surgery. Several researchers have sought interventions that would decrease the incidence of this complication. Pharmaceutical interventions have been sought to reduce the degree of reperfusion injury, increase vasoactivity, and alter the rheology of blood. Additionally, mechanical means of ischemic preconditioning have also been studied. However, few studies have been conducted to determine the effects oxygen therapeutic drugs. It is the goal of this study to determine whether the oxygen therapeutic HBOC-201 (Hemopure ®) altered flap survival in a rat model of planned epigastric flap failure.
Methods: 83 male Sprague-Dawley rats were randomly assigned to one of four groups: group 1: Control (surgical creation of flap only), group 2: HBOC-201 (1gm/dl IV) administered Q 48 hours, group 3: HBOC-201 (2gm/dl IV) administered Q48 hours, and group 4: Hemodilution (Lactated Ringers) administered Q 48 hours. A ventral fasciocutaneous flap (5X7cm) was elevated, based on the inferior epigastric vessels. Unilateral ligation and division of the epigastric vessels was then performed and the skin flap replaced and sutured with a running suture. Animals were examined daily and euthanized on day seven. Prior to euthanasia, digital photographs were taken of each rat. The digital images were then analyzed for total area of the flap and area of necrosis using ImagePro ® software. Using the calculated percentage of necrosis for each animal, a mean value for percentage necrosis was obtained for each animal group and used for statistical analysis. Additionally, paraffin imbedded tissue slides were prepared from a representative area of the flap. These slides were used for Hemotoxilin &Eosin (H&E) preparations in which the levels of inflammation, venous congestion, and neovascularization were assessed.
Results: Animals in both HBOC-201 groups demonstrated less percentage of necrosis than the control and LR groups. Animals in group 2 demonstrated decreased area of necrosis when compared to the control group (9.14% v. 22.24%, p=0.014). Similar results were also identified in group3 (12.225% v. 22.24%) however did not reach statistical significance. Additional comparison of groups 2 and 3 suggested decrease area of necrosis when compared to the hemodilution group, however did not meet statistical significance.
Conclusion: The oxygen therapeutic HBOC-201 appears to decrease the area of necrosis at a dose of 1gm/dl in a rat model of epigastric flap failure. Comparison of the groups that received HBOC-201 to the hemodilution group (LR) suggests that this effects is not purely explained by the hemodilution and that the intrinsic properties of HBOC-201 (i.e. its oxygen carrying capacity, its resultant decrease in viscosity, or the antioxidant effects of NAC) may lend to improved flap survival. Additionally, investigation of similar products has demonstrated decrease transfusion requirements in subjects treated with HBOCs and thus may greatly impact the care of patients in many specialties. Further investigation of this drug and its effects on flap survival is warranted.
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