Stadelmann W K, Hess D B, Robson M C, Greenwald D P
Division of Plastic Surgery, University of Louisville, KY 40292, USA.
Microsurgery. 1998;18(6):354-61; discussion 362-3. doi: 10.1002/(sici)1098-2752(1998)18:6<354::aid-micr2>3.0.co;2-v.
Multiple drugs have been used in experimental skin flap models to reduce the effects of reperfusion ischemia. The effects of antiproteases, however, have not been studied. A skin flap ischemia reperfusion model was developed in the rat to study the effects that aprotinin, a broad-spectrum antiserine protease, would have on skin flap viability. Thirty-two male rats underwent elevation of a ventral pedicled skin flap based on the superficial inferior epigastric artery. The flaps were subjected to 10 hr of warm ischemia by clamping the neurovascular pedicle followed by reperfusion. Aprotinin or saline (control) was administered systemically via the contralateral femoral vein either before or after the ischemic insult. Full-thickness skin biopsies were obtained at 1, 8, and 24 hr into reperfusion. Biopsies were evaluated for neutrophil concentration (using a myeloperoxidase [MPO] assay) and thromboxane B2 [TxB2] content. Flap survival was calculated at 1 week using standardized photography and computer-assisted digital imaging. Aprotinin given before an ischemic insult significantly improved flap survival compared to saline controls (52.3% alive vs. 29.6%, P = 0.0132, unpaired t-test). Aprotinin given after ischemia did not significantly influence flap survival (28.8% vs. 34.4% in saline controls, P = 0.708). MPO levels in the aprotinin preischemia treatment group were significantly less at 1 and 8 hr into reperfusion, indicating decreased neutrophil numbers. No statistical difference in TxB2 levels was noted in either group at any time after reperfusion. Aprotinin significantly improves skin flap survival when given prior to but not after an ischemic insult. Aprotinin appears to lower the concentration of neutrophils in skin flaps pretreated with the drug. Reperfused skin flap levels of thromboxane B2 are unaffected by the pre- or postischemic administration of aprotinin.
多种药物已被用于实验性皮瓣模型，以减轻再灌注缺血的影响。然而，抗蛋白酶的作用尚未得到研究。在大鼠中建立了皮瓣缺血再灌注模型，以研究广谱抗丝氨酸蛋白酶抑肽酶对皮瓣存活的影响。32只雄性大鼠接受了基于腹壁下浅动脉的腹侧带蒂皮瓣的掀起。通过夹闭神经血管蒂使皮瓣经历10小时的热缺血，随后进行再灌注。抑肽酶或生理盐水（对照）在缺血损伤前或后通过对侧股静脉全身给药。在再灌注1小时、8小时和24小时时获取全层皮肤活检样本。对活检样本进行中性粒细胞浓度（使用髓过氧化物酶[MPO]测定法）和血栓素B2 [TxB2]含量的评估。在1周时使用标准化摄影和计算机辅助数字成像计算皮瓣存活率。与生理盐水对照组相比，在缺血损伤前给予抑肽酶显著提高了皮瓣存活率（存活52.3% vs. 29.6%，P = 0.0132，未配对t检验）。缺血后给予抑肽酶对皮瓣存活率没有显著影响（28.8% vs. 生理盐水对照组的34.4%，P = 0.708）。抑肽酶缺血预处理组在再灌注1小时和8小时时的MPO水平显著降低，表明中性粒细胞数量减少。再灌注后任何时间两组的TxB2水平均无统计学差异。在缺血损伤前而非缺血后给予抑肽酶可显著提高皮瓣存活率。抑肽酶似乎降低了用该药物预处理的皮瓣中的中性粒细胞浓度。再灌注皮瓣的血栓素B2水平不受抑肽酶缺血前或缺血后给药的影响。
