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Inhibition of vein graft intimal hyperplasia by free radical quenching and photodynamic therapy
Anti-Neutrophil Antibody and Anti-C5 Antibody Allows Inhibition of Acute Vein Graft Thrombosis After Photochemical Therapy
Photodynamic therapy inhibits intimal hyperplasia in arteriousvenous fistula
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusett
Laser-Induced Shock Waves Enhance Sterilization of Infected Vascular Prosthetic Grafts
Background and Objective: Bacteria that cause infection
of vascular prosthetic grafts produce an exopolysaccharide
matrix known as biofilm. Growth in biofilms
protects the bacteria from leukocytes, antibodies and
antimicrobial drugs. Laser-generated shock waves (SW)
can disrupt biofilms and increase drug penetration. This
study investigates the possibility of increasing antibiotic
delivery and sterilization of vascular prosthetic graft.
Study Design/Materials and Methods: Strains of
Staphylococcus epidermidis and S. aureus were isolated
from infected prosthetic grafts obtained directly from
patients. Dacron grafts were inoculated with the isolated
bacteria, which were allowed to form adherent bacterial
colonies. The colonized grafts underwent the following
treatments: (a) antibiotic (vancomycin) alone; (b) antibiotic
and SW (c) saline only; and (d) saline and SW. Six hours
after treatment, the grafts were sonicated, the effluent was
cultured and the colony forming units (CFU) were counted.
Results: CFU recovered from control grafts colonized by
S. epidermidis were comparable: saline, 3.05108 and
saline SW 3.31108. The number of S. epidermidis CFU
diminished to 7.61106 after antibiotic treatment but the
combined antibiotic SW treatment synergistically
decreased CFU number to 1.27104 (P<0.001). S. aureus
showed a higher susceptibility to the antibiotic: 2.26106
CFU; antibiotic SW treatment also had an incremental
effect: 8.27104 CFU (P<0.001).
Conclusions: This study demonstrates that laser-generated
shock waves have no effects alone, but can enhance
the effectiveness of antibiotics against bacteria associated
with prosthetic vascular graft biofilms, suggesting that
this treatment may be of value as adjunctive therapy for
prosthetic graft infections. Lasers Surg. Med. 29:448–454,
2001. ß 2001 Wiley-Liss, Inc
Gamma Irradiation Modulates Vascular Smooth Muscle Cells and Extracellular Matrix Function: Implications for Neointimal Development
Objective: Migration of vascular smooth muscle cells (SMCs) into the subintimal space, and their proliferation and
resultant deposition of extracellular matrix are key processes in the development of intimal hyperplasia, leading to
vascular recurrent stenosis. The purpose of this study was to investigate the effects of clinically administered doses of
-radiation on SMCs and extracellular matrix proteins in vitro, to better understand how it impinges on cellular and
extracellular components of recurrent stenosis.
Methods: The effects of -irradiation (10, 20 Gy) on SMC migration into three-dimensional collagen matrix gels was
quantitated by calibrated light microscopy, and the release of metalloproteinases into conditioned media was investigated
with an enzyme-linked immunosorbent assay and zymography. Collagen production was assayed with [3H]-proline
incorporation, and SMC phenotype changes with confocal microscopy with a fluorescent -actin antibody. The effect of
-irradiation on extracellular matrix was investigated by quantitating untreated SMC proliferation (3H-thymidine
incorporation) on irradiated endothelial cell– derived matrix and by assessing structural collagen matrix changes with
sodium dodecylsulfate polyacrylamide gel electrophoresis. All groups were compared with nonirradiated control groups.
Results: SMC vertical migration was significantly decreased by -irradiation (48% and 55%, respectively; P < .0001).
Irradiation did not generate measurable matrix protein crosslinks, nor did it alter the production of metalloproteinases
or collagen synthesis. However, -irradiation decreased the ability of extracellular matrix to induce nonirradiated SMC
proliferation (15% reduction; P .0028). Moreover, -irradiation reversed the secretory phenotype of cultured SMCs to
a contractile type.
Conclusions: The -irradiation–induced reduction of cellular migration, changes in SMC phenotype, and functional
activity of matrix-bound factors, and no measurable effects on the production of extracellular matrix proteins, may in part
explain the diverse effects of -irradiation on the restenotic response. (J Vasc Surg 2004;39:1097-1103.)
Clinical Relevance. -Irradiation has found clinical application in the prevention of vascular recurrent stenosis. Although
short-term results indicate reduction of recurrent stenosis, late results are not so promising. This in vitro study
interrogated the biologic effects of -irradiation on vascular smooth muscle cells (SMCs) and their extracellular matrix,
to enable understanding of how it affects recurrent stenosis. The results are mixed: -irradiation does not inhibit protein
synthesis, but does inhibit SMC three-dimensional migration, enhances SMC transformation to a contractile phenotype,
and reduces the functional activity of matrix-associated growth factors. This provides insight into how -irradiation alters
the biologic response of arteries after intervention.
Vascular recurrent stenosis is a post-interventional multifactorial
process that involves the migration of smooth
muscle cells (SMCs) and myofibroblasts into the subintimal
space, and their proliferation and deposition of extracellular
matrix proteins.1,2 Recurrent stenosis remains the major
drawback to cardiovascular interventions, and therefore
methods to preven
Free Radical Quenching Enables Photodynamic Therapy Inhibition of Vein Graft Intimal Hyperplasia
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusett
Improved sterilization of prosthetic vascular graft using shock waves
Abstract published on Lasers Surg Med 2001, Suppl. 2
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