The proposed studies offer a comprehensive approach for ranking various factors with regard to their relative importance in lack of reflow following microsurgical anastomosis and functional failure of replanted tissue to survive. As an adjunct, the investigators propose to evaluate a number of pharmacologic agents that have shown promise as inhibitors of reperfusion injury and failure. Emphasis will be placed on the functional result after intervention. Specifically, the applicants will: (1) evaluate the effects of low molecular weight heparin alone, and in combination with thrombolytic agents such as streptokinase, urokinase and tissue plasminogen activator, on thrombosis formation at arterial and venous anastomosis sites; (2) determine the effects of specific pharmacologic agents on the microcirculation of innervated and denervated tissues after reperfusion injury with emphasis on leukocyte adhesion and migration; and (3) quantify effects of specific pharmacologic agents on innervated and denervated muscles with different fiber types. Subsequent function of the muscles will be measured by contractile ability along with PMN adherence and nitric oxide and nitric oxide synthase activity.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Special Emphasis Panel (ZRG4-ORTH (02))
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Duke University
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United States
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Tan, Xiangling; Qi, Wen-Ning; Gu, Xiaosong et al. (2006) Intermittent pneumatic compression regulates expression of nitric oxide synthases in skeletal muscles. J Biomech 39:2430-7
Park, Jong Woong; Qi, Wen-Ning; Liu, John Q et al. (2005) Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice. Microsurgery 25:606-13
Park, Jong Woong; Qi, Wen-Ning; Cai, Yongting et al. (2005) Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse. Am J Physiol Heart Circ Physiol 289:H181-7
Barker, Joseph U; Qi, Wen-Ning; Cai, Yongting et al. (2005) Addition of nitric oxide donor S-nitroso-N-acetylcysteine to selective iNOS inhibitor 1400W further improves contractile function in reperfused skeletal muscle. Microsurgery 25:338-45
Qi, Wen-Ning; Zhang, Li; Chen, Long-En et al. (2004) Nitric oxide involvement in reperfusion injury of denervated muscle. J Hand Surg Am 29:638-45
Qi, Wen-Ning; Chaiyakit, Pruk; Cai, Yongting et al. (2004) NF-kappaB p65 involves in reperfusion injury and iNOS gene regulation in skeletal muscle. Microsurgery 24:316-23
Gowda, Charan; Toomayan, Glen A; Qi, Wen-Ning et al. (2004) The effects of N(omega)-propyl-L-arginine on reperfusion injury of skeletal muscle. Nitric Oxide 11:17-24
Patel, Prerana; Qi, Wen-Ning; Allen, Diane M et al. (2004) Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle. Microsurgery 24:324-31
Qi, Wen-Ning; Chen, Long-En; Zhang, Li et al. (2004) Reperfusion injury in skeletal muscle is reduced in inducible nitric oxide synthase knockout mice. J Appl Physiol 97:1323-8
Zhang, Li; Looney, Colin G; Qi, Wen-Ning et al. (2003) Reperfusion injury is reduced in skeletal muscle by inhibition of inducible nitric oxide synthase. J Appl Physiol 94:1473-8

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