Research InterestsPeripheral vascular physiology; vasospasm; thrombosis; angiogenesis; wound healing; ischemia/reperfusion injury in vivo and in vitro.
Degrees: Ph.D 1975
Affiliations: Institute of Medical Sciences, University of Toronto
1. We are using the established rat dorsal skin flap model to investigate the efficacy and mechanism of angiogenic cytokine gene therapy for optimal augmentation of skin flap viability.
2. We are using our established ex vivo human skeletal muscle model to investigate the efficacy, mechanism and therapeutic potential in hypoxic preconditioning and postconditioning of human skeletal muscle against reoxygenation (reperfusion) injury.
Detailed Description: Skin and muscle flaps, both pedical and free, are routinely used to reconstruct defects resulting from injury, excision of tumor, ulceration, or congenital malformation. The clinical problem is that flap failure as a result of ischemic necrosis occurs in both pedicle and free flaps. In free flap alone, ischemia necrosis occurs in 5-10% of patients, even in experienced hands. Flap necrosis can be partial or total. Flap failure is time-consuming and costly because it requires repeated surgery and prolonged hospitalization. In addition, repeated surgery increases the incidence of donor site deformity and/or morbidity, with devastating effects on the patient. Therefore, we need to understand the pathophysiology of ischemic necrosis in skin and muscle flap surgery because this information may lead us to develop effective pharmacological therapies to prevent or salvage flap failure. My research focus, importance, and significance in the pathophysiology and pharmacology of flap surgery can be found in my review publications
Human skeletal muscle in vitro, skin flaps in vivo, in vitro skeletal muscle, adenovirus, gene expression analysis, immunohistochemistry, isolated vessel preparation, RIA, vessel cannulation, western blot, animal surgery room, culture incubator
Analytical balances, benchtop centrifuge, blotting apparatus, confocal microscope, culture hood, culture incubators, dissecting microscope, infusion apparatus, low- and high-speed centrifuge, low and ultralow freezers, stirrer/hot plate, water baths
Stefan Hofer, M.D., Ph.D., Department of Surgery, University of Toronto, Canada
Anne O’Neil, M.D., Ph.D., Department of Surgery, University of Toronto, Canada
Toni Zhong, M.D., Ph.D., Department of Surgery, University of Toronto, Canada
Publications and Awards
A short list of selected important publications:
Pang CY, Forrest CR, Xu H, Zhang J, Lipa JE, and Neligan P. Role and mechanism of endothelinB (ETB) receptors in mediating ET-1-induced vasoconstriction in pig skin. American Journal of Physiology 275(4): R1066-1074, 1998.
Lipa JE, Neligan P, Perrault TM, Baribeau J, Levine R, Knowlton R, and Pang CY. Vasoconstrictor effect of endothelin-1 (ET-1) in human skin: The role of ETA and ETB receptors. American Journal of Physiology 276(2): H359-H367, 1999.
Hopper RA, Forrest CR, Zhong A, He W, Xu H, Rutka J, and Pang CY. Role and mechanism of protein kinase C in ischemic preconditioning of pig skeletal muscle against infarction. American Journal of Physiology 279(2): R666-R676, 2000.
Zhang J, Lipa JE, Black CE, Huang N, Neligan PC, Ling FTR, Levine RH, Semple JL, and Pang CY. Pharmacological characterization of vasomotor activity of human musculocutaneous perforator artery and vein. Journal of Applied Physiology 89(6): 2268-2275, 2000.
Black CE, Huang N, Neligan PC, Levine RH, Lipa JE, Forrest CR, Lintlop S, and Pang CY. Effect of nicotine on vasoconstrictor and vasodilator responses in human skin vasculature. American Journal of Physiology 281(4): R1097-R1104, 2001.
A short list of selected important abstracts in the past 10 years:
Moses MA, Huang N, Ashrafpour H, Neligan PC, Forrest CR, Lipa JE, and Pang CY. Na+/H¯ exchange (NEH) inhibitor is more effective than ischemic preconditioning (IPC) in protection of muscle flaps against ischemia/reperfusion (I/R) injury. Proceeding Plastic Surgery Research Council Meeting (U.S.A.) Abstract #9B, 2005.
Ashrafpour H, Huang N, Khan A, Neligan PC, Forrest CR, Kontos C, and Pang CY. Adenovirus mediated vascular endothelial growth factor–165 (Ad.CMV.VEGF165) gene therapy in augmentation of rat skin flap viability: Dose-dependent effect and mechanism of action. Proceeding Plastic Surgery Research Council Meeting (U.S.A.), Abstract #51A, 2005.
McAllister SE, Moses MA, Huang N, Ashrafpour H, Neligan P, Forrest CR, Lipa JE, and Pang CY. Protection of muscle flaps against ischemia/reperfusion injury with cariporide-induced Na+/H+ exchange inhibition. Canadian Journal of Plastic Surgery 13: 90, 2005.
McAllister SE, Neligan PC, Ashrafpour H, Huang N, Lipa JE, Forrest CR and Pang CY. Efficacy and mechanism of postischemic conditioning (PostC) for salvage of ischemic skeletal muscle from ischemia/reperfusion (I/R) injury. Proceeding Plastic Surgery Research Council Meeting (U.S.A.) Abstract #14A, 2005.
Martou G, O’Blenes C, Huang N, McAllister S, Neligan PC, Pang CY, and Lipa JE. Ischemic preconditioning protects human skeletal muscle against ischemia/reperfusion injury in vitro. Proceeding Plastic Surgery Research Council Meeting (U.S.A.), Abstract #51B, 2006.