The major emphasis of the Vascular Surgery Research Laboratory is to develop therapeutic strategies to ameliorate vascular injury and the effects of ischemia and reperfusion injury. The laboratory uses in vitro and in vivo models (porcine and murine) to assess the response of vascular smooth muscle and endothelial cells to mechanical injury, which mimics intimal hyperplasia. Mouse models are used to study cellular and tissue responses to acute ischemia reperfusion in spinal cord and skeletal muscle.
The Vascular Biology Research Laboratory has developed collaboration with the Plastic and Reconstructive Surgery Laboratory in evaluating the utility of pharmacologic agents in ameliorating tissue injury following hind limb ischemia reperfusion. Collaboration also exists with the Shriners’ Burn Institute Anesthesia Research Laboratory, into understanding the signal transduction pathways responsible for stimulating skeletal muscle regeneration following hind limb ischemia reperfusion.
A fundamental strength of the research laboratory is the clinical relevance of our experimental models. Our studies into spinal cord ischemia reperfusion employ a murine model. Experiments from our and other labs demonstrate that the murine model of thoracic aortic ischemia reperfusion replicates the anterior cord injury observed in humans following repair of the thoracic aorta. The histologic findings in the spinal cord tissue are identical to patients presenting with this devastating clinical problem. The murine model of ischemia reperfusion uses orthodontic rubber bands to achieve reproducible levels of hind limb ischemia. The bands allow specific functional evaluation of skeletal muscle contractile response to ischemia reperfusion rather than crush injury.
The laboratory’s effort to understand the pathobiology of intimal hyperplasia began with collaborations in the Wellman Laser Laboratory. In landmark experiments, the laboratory demonstrated the ability to treat and prevent intimal hyperplasia using photosensitizing agents and light irradiation. Our current efforts are geared towards creating a large animal model of intimal hyperplasia in the pig, and performing pre-clinical testing in this model. This model will allow us to determine the appropriate dosimetry for laser irradiation in human studies.
The Vascular Surgery Research Laboratory is equipped with a 900-square-foot analytical laboratory and a 400-square-foot histology/tissue culture facility. The lab is equipped with real-time PCR cycler, a UV, colorimeteric and fluorescent ELISA plate reader, microtome, -80 freezers, a Nikon microscope mounted with a digital camera, and a small animal operating room. There are multiple benches which provide computer based access to the internet and the Harvard/Mass General Digital Library. An office suite and conference room for fellows, secretarial staff and laboratory personnel is immediately adjacent to the laboratory facilities.
Michael T. Watkins, MD, FACS, Associate Professor of Surgery, Harvard Medical School
Glenn M. LaMuraglia, MD, FACS, Associate Professor of Surgery, Harvard Medical School
Hassan Al-Badawi, MD, Instructor in Surgery, Harvard Medical School
Jin-Hyung Yoo, MS, Research Assistant
The Role of Poly ADP- Ribose Polymerase in Skeletal Muscle Regeneration
Photodynamic Therapy for Intimal Hyperplasia in a Porcine Model
Effect of Hypothermia on Spinal Cord Ischemia Reperfusion Injury
Our research fellows usually come directly from the Vascular Surgery Residency Program. Each of the two first year fellows spend six months in the lab.
Kossodo S, LaMuraglia GM. Clinical potential of photodynamic therapy in cardiovascular disorders. Am J Cardiovasc Drugs 2001;1:15-21.
Heckenkamp J, Nigri GR, Waterman PR, Overhaus M, Kossodo SC, Lamuraglia GM. Gamma-irradiation modulates vascular smooth muscle cell and extracellular matrix function: Implications for neointimal development. J Vasc Surg 2004;39:1097-103.
Nigri GR, Kossodo S, Waterman P, Fungaloi P, LaMuraglia GM. Free radical attenuation prevents thrombosis and enables photochemical inhibition of vein graft intimal hyperplasia. J Vasc Surg 2004;39:843-9.
Casey PJ, Black JH, Szabo C, et al. Poly(adenosine diphosphate ribose) polymerase inhibition modulates spinal cord dysfunction after thoracoabdominal aortic ischemia-reperfusion. J Vasc Surg 2005;41:99-107.
Albadawi H, Crawford RS, Atkins MD, Watkins MT. Role of poly(ADP-ribose) polymerase during vascular reconstruction. Vascular 2006;14:362-5.
Black JH, Casey PJ, Albadawi H, Cambria RP, Watkins MT. Poly adenosine diphosphate-ribose polymerase inhibitor PJ34 abolishes systemic proinflammatory responses to thoracic aortic ischemia and reperfusion. J Am Coll Surg 2006;203:44-53.
Conrad MF, Albadawi H, Stone DH, Crawford RS, Entabi F, Watkins MT. Local administration of the Poly ADP-Ribose Polymerase (PARP) inhibitor, PJ34 during hindlimb ischemia modulates skeletal muscle reperfusion injury. J Surg Res 2006;135:233-7.
Crawford RS, Hashmi FF, Jones JE, et al. A novel model of acute murine hindlimb ischemia. Am J Physiol Heart Circ Physiol 2007;292:H830-7.
Albadawi H, Patton GM, Bratton CF, Peterson BG, Watkins MT. Human microvascular endothelial synthesis of interleukin-8 during in vitro ischemia and reperfusion. J Cell Biochem 2007;100:412-20.
Entabi F, Albadawi H, Stone DH, Sroufe R, Conrad MF, Watkins MT. Hind limb ischemia-reperfusion in the leptin receptor deficient (db/db) mouse. J Surg Res 2007;139:97-105.
Abbruzzese TA, Albadawi H, Kang J, et al. Enoxaparin does not ameliorate limb ischemia-reperfusion injury. J Surg Res 2008;147:260-6.
Kang J, Albadawi H, Patel VI, et al. Apolipoprotein E-/- mice have delayed skeletal muscle healing after hind limb ischemia-reperfusion. J Vasc Surg 2008;48:701-8.
McCormack MC, Kwon E, Eberlin KR, et al. Development of reproducible histologic injury severity scores: skeletal muscle reperfusion injury. Surgery 2008;143:126-33.
Hua HT, Albadawi H, Entabi F, et al. Effects of acute global venous obstruction and unfractionated heparin on muscle cytokine synthesis. Ann Vasc Surg 2009;23:108-15.