S-nitrosoglutathione reduces nonocclusive thrombosis rate following balloon overstretch injury and intracoronary irradiation of porcine coronary arteries.
OBJECTIVE
Intracoronary radiation (IR) suppresses neointima formation following balloon injury in animal models. High doses of radiation exacerbate thrombosis and delay re-endothelialization. The free radical nitric oxide (NO) has been reported to inhibit platelet aggregation, reduce neointimal hyperplasia, and stimulate re-endothelialization. This study examined the effects of a chemical NO donor on neointima formation, thrombosis, and healing of irradiated porcine coronary arteries.


METHODS
Vascular lesions were created in the coronary arteries of 59 domestic swine by overstretch balloon injury. Arteries were then left untreated or were treated with intracoronary gamma-radiation using Iridium-192 in each artery to deliver 5 or 15 Gy at 2 mm from the center of the source. The chemical NO donor S-nitrosoglutathione (GSNO) was infused i.v. at a rate of 250 microg/min for 10 min before injury, followed by a continuous infusion for 60 min. Animals were euthanized at 14 days and their arteries were analyzed for histomorphometric indices of proliferation and thrombosis.


RESULTS
A dose of 15 Gy reduced the ratio of intimal area to medial fracture length (IA/FL) versus control (0.06 +/- 0.05 0.54 +/- 0.10 [p < 0. 001]) but increased the nonocclusive thrombosis rate compared to controls (85% vs. 30%; p < 0.05). A low dose of 5 Gy did not affect neointima formation. Treatment with GSNO reduced thrombosis in all treated groups: control, 15%; 5 Gy, 18%; and 15 Gy, 35% (p < 0.05) without affecting neointima formation.


CONCLUSIONS
Systemic administration of GSNO during balloon injury and IR was tolerated well by the swine and resulted in reduction of the thrombosis rate, especially at high doses, without apparent effect on neointima formation.
Vodovotz
Y
Y
Washington Hospital Center, Washington, DC 20010, USA.
Waksman
R
R
Cook
J A
JA
Kim
W H
WH
Chan
R
R
Seabron
R
R
Collins
S D
SD
Pierre
A
A
Bramwell
O
O
Wink
D
D
Mitchell
J B
JB
Leon
M B
MB
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels / Q000293:injuries / Q000528:radiation effects*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007496:Iridium Radioisotopes / Q000627:therapeutic use*; D023421:Models, Animal; D009603:Nitroso Compounds / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011853:Radiobiology; D026422:S-Nitrosoglutathione; D013552:Swine; D017539:Tunica Intima / Q000293:injuries / Q000528:radiation effects*
D007496:Iridium Radioisotopes; D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D026422:S-Nitrosoglutathione; D005978:Glutathione