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Vascular Surgery

Principal Investigators:
William M. Abbott, MD
Richard P. Cambria, MD
David C. Brewster, MD
Glenn M. LaMuraglia, MD
Christopher Kwolek, MD

Zenith AAA Endovascular Prosthesis (COOK, Incorporated)
The Zenith AAA device is an endovascular graft designed to treat infrarenal abdominal aortic aneurysms with a less invasive technique. It is a modular system utilizing a unique deployment system. The graft is comprised of Twillweave polyester fabric supported externally by stainless steel stents. A unique advantage of this device is the capability of suprarenal implantation due to the uncovered, barbed, proximal stents. Balloon seating is used to maximize secure stent attachment. These features allow for greater flexibility in treating aneurysms with endovascular technology.

Bifurcated EXCLUDER Endovascular Prosthesis (W.L. Gore)
A trend in surgery over the past decade has been to develop less invasive procedures to accomplish treatment goals with reduced operative risks and complications. One such evolving technique for less invasive vascular surgery involves the use of endovascular grafts that combine metallic supporting structures and prosthetic graft technologies. The use of endovascular prostheses in the primary treatment of infrarenal AAA has the potential to lower mortality and morbidity especially in high-risk patients. The Bifurcated EXCLUDER Endoprosthesis is a device that allows for primary endovascular repair of infrarenal AAAs and is intended to be used as an intraluminal blood conduit.

Principal Investigators:
William M. Abbott, M.D.
Michael T. Watkins, M.D.
Glenn M. LaMuraglia, M.D.

Biodynamic and Metabolic Factors in Vein Graft Hyperplasia
Our laboratory has pursued the central hypothesis that fluid mechanical forces trigger biological consequences on the cells of the vascular wall. In some instances, these forces may initiate pathophysiological changes and in others, they may promote vessel health. The types of forces and types of vascular wall cells (arterial vs. venous, microvascular vs. macrovascular) ultimately determine the outcome. Delineation of the functional effects of hemodynamic forces (pressure, shear stress, wall strain) on vascular wall cells is a major focus of research in the Vascular Surgery Research Laboratory. Recently our laboratory has determined that in addition to the biomechanical forces, metabolic factors (i.e. oxidative stress) may also trigger pathophysiologic changes in the vein graft wall. The specific aims of this project involve defining the signal transduction pathways primarily responsible for activation of proliferative and prothrombotic pathways. If specific pathways can be identified, it may be possible to target them with molecular or pharmacologic techniques.

Principal Investigator:
Richard P. Cambria, M.D.
J. Kenneth Davison, M.D.

Spinal Cord Protection During Thoracoabdominal Aortic Surgery
The investigators continue to prospectively evaluate the technique and results achieved with epidural cooling for spinal cord protection during complex aortic surgery. This technique was developed at the MGH and nearly 200 patients have been managed with it over the past 5 ½ years. Results have been favorable when compared to institutional historical controls, published predictive models for cord injury after TAA surgery, and other strategies for spinal cord protection.

Stent Graft Repair of Thoracic Aortic Aneurysm
Prospective clinical evaluation of a PTFE stent graft for repair of thoracic aortic aneurysms utilizing concurrent conventional surgery controls. Heretofore, the few thoracic aortic stent grafts implanted at the MGH were relatively crude, custom-made constructs. The device under investigation is an about to be approved (for investigational use) PTFE graft/Nitinol stent construct with unique deployment mechanics. These design features will presumably expand the stent graft technology to thoracic aortic lesions. Preliminary experience at the MGH with a single “compassionate use” case utilizing this new graft was most satisfactory.

Principal Investigator:
Glenn M. LaMuraglia, M.D.

Evaluation of PDT to prevent intimal hyperplasia
Intimal hyperplasia, the excessive proliferation of blood vessel cells and the deposition of matrix proteins, is a significant clinical problem, and the most frequent cause of late failure following vascular reconstructive surgery. In 1991, this group was the first to use photodynamic therapy in an animal model to eliminate those cells responsible for intimal hyperplasia thus inhibiting the process. We are currently involved in pre-clinical studies focussing on optimizing photosensitizer and light delivery to inhibit intimal hyperplasia.

Arterial remodeling after PDT and ionizing radiation
Experiments are underway using an in vitro model to mimic smooth muscle cell migration and deposition of extracellular matrix, to investigate the mechanisms responsible for these processes. The effects of PDT and ionizing radiation on these parameters are being studied. In addition, very little is known about the three-dimensional architecture and anatomy in normal and diseased blood vessels. Basic studies using laser confocal scanning microscopy are being undertaken to fully understand how changes in vessel structure may affect vascular biology after injury.

PDT development of vascular biografts
Another potential application of vascular PDT is in the preparation of a vascular xenograft - a vascular bypass graft that can be placed in humans but be of other species origin. In the past, the use of xenografts has been limited due to rejection. This rejection process, however, can be significantly diminished using photodynamic therapy. Vascular PDT eliminates the main immunologic stimulus for rejection - the cells present in the arterial wall, and also welds the matrix to limit the induction of inflammation while maintaining the structural integrity of the vessel. Parallel studies using vein bypass grafts are being pursued to determine if vein graft stenoses can be inhibited. Multiple efforts are also trying to elucidate the molecular mechanisms responsible for vein graft and xenograft failure.

PDT in vascular graft infections
Another area of interest is in prosthetic graft infections, a relatively common and potentially fatal complication after vascular surgery. Bacteria responsible for these infections form biofilms, rendering them inaccessible to conventional antibiotic treatment. New methods are being investigated to deliver bacteriocidal drugs to the bacteria infecting the prosthetic material and also using photosensitizers and light to kill the bacteria.

Laser-assisted thrombolysis for treatment of A-V fistulas
There is no rapid percutaneous method for opening dialysis access AV grafts and fistulas. With the ability to use cavitation from a pulsed dye laser tuned to absorb in the hemoglobin band, selective ablation of the thrombus, but not the vessel wall or the graft material, can be performed. A physician-sponsored IDE clinical trial has been established using short-pulsed, low power laser light to enhance pharmacologic thrombolysis of AV fistula grafts in humans. Another approach using PDT to improve the patency and long-term efficacy of AV fistulas is being investigated.

Principal Investigators:
Michael T. Watkins, MD
Glenn LaMuraglia, MD
Hassan Albadawi, MD

Remote and Local Tissue Injury During Ischemia/Reperfusion
Two decades of research in this field has clearly implicated a role for reactive oxygen metabolites and neutrophils in the development of reperfusion injury. Over this period of time, the postoperative complications following urgent lower extremity revascularization changed. Early on, renal failure, respiratory failure and compartment syndromes were the major early complications on postoperative day one. More recently, in-hospital cardiopulmonary complications on postoperative day three appear to be the major source of life-threatening complications. These experiments are geared towards understanding changes in the profile of cytokines and procoagulant factors during and following ischemia – reperfusion. We hypothesize that proinflammatory, cytokine mediated systemic stresses which start during ischemia potentiate the metabolic problems in the revascularized lower extremity. The cytokines likely promote a pro-inflammatory response which persists for weeks/months in the leg, heart, kidney and lungs. Using a murine model of hindlimb IR injury, we are exploring the molecular basis of the proinflammatory response. An in vitro model of human microvascular endothelial cells is also being used to explore the cellular signal pathways activated during clinically relevant periods of Ischemia/Reperfusion.

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