Photodynamic therapy of vein grafts: suppression of intimal hyperplasia of the vein graft but not the anastomosis.
OBJECTIVE
There is no clinically useful therapy for the suppression of vein bypass graft intimal hyperplasia (IH). Photodynamic therapy (PDT), a technique that uses light to activate otherwise biologically inert photosensitizers to produce cytotoxic effects, has been demonstrated to successfully inhibit experimental IH in balloon-injured arteries. The purpose of this study was to investigate the efficacy of PDT as a method to reduce vein graft IH.


METHODS
Reversed external jugular vein bypass grafts of the common carotid artery were performed in 28 male Sprague-Dawley rats. The animals received either chloroaluminum sulfonated phthalocyanine (2.5 mg/kg intravenously) 24 hours before the ex vivo irradiation of the vein grafts (VG) with 100 joule/cm2 at 675 nm (PDT VG) or saline solution as control (CON VG). Preharvest bromodeoxyuridine was administered to label proliferating cells. All vein grafts were perfusion fixed within 96 hours for a pilot study or at 2 and 4 weeks for the main study. Histology, immunohistochemistry, and morphometric analysis were performed.


RESULTS
There was no acute thrombus formation in the hypocellular PDT VG with occasional platelets but no leukocytes adherent to the luminal surface. Intimal areas of the PDT VG were 18% at 2 weeks and 53% at 4 weeks of the CON VGs (p < 0.05). Medial areas and percent of stenoses were also significantly less in PDT than in CON VG. However, intimal hyperplasia noted in the longitudinal sections within 2 mm of the anastomoses did not demonstrate a difference between PDT and CON VG. Intimal hyperplasia of both PDT and CON VG consisted of smooth muscle cells, verified by immunohistochemistry. Bromodeoxyuridine-labeled cells were more abundant in 2-week than in 4-week specimens, were found most frequently in the intimal areas of the CON VG body, and were equivalent in the anastomoses of PDT VG and CON VG.


CONCLUSIONS
These data suggest that PDT of vein grafts suppresses the development of IH in the body of the vein graft but does not affect IH adjacent to the anastomoses. The artery may be the source of proliferating smooth muscle cells that contribute to the anastomotic vein graft IH.
LaMuraglia
G M
GM
Division of Vascular Surgery, Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Klyachkin
M L
ML
Adili
F
F
Abbott
W M
WM
D000714:Anastomosis, Surgical; D000818:Animals; D001792:Blood Platelets / Q000473:pathology; D001973:Bromodeoxyuridine; D017536:Carotid Artery, Common / Q000601:surgery; D002455:Cell Division; D006965:Hyperplasia; D007211:Indoles / Q000627:therapeutic use; D007601:Jugular Veins / Q000473:pathology / Q000637:transplantation; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*; D014680:Veins / Q000473:pathology / Q000637:transplantation*
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C052736:chloroaluminum tetrasulfophthalocyanine; D001973:Bromodeoxyuridine