The Effects of Radiation Using Ho-166 on Endothelial Function in a Porcine Coronary Model

Rhew, Jay Young; Jeong, Myung Ho; Lee, Sang Rok; Hong, Young Joon; Lee, Seng Hyun; Park, Ok Young; Jeong, Woo Kon; Kim, Weon; Kim, Ju Han; Yum, Ju Hyup; Song, Ho Cheon; Bom, Hee Seung; Park, Kyung Bae; Ahn, Young Keun; Cho, Jeong Gwan; Park, Jong Chun; Baik, Yung Hong; Kang, Jung Chaee

Abstract

BACKGROUND AND OBJECTIVES
It has been reported that intracoronary radiation therapy (ICRT) using a Ho-166 coated balloon inhibits restenosis of porcine coronary arteries. However, the consequences of ICRT on coronary artery endothelial function are unknown. The aim of this study is to investigate the effects of ICRT using a Ho-166 balloon on coronary artery endothelial function and vasomotor reactivity.
MATERIALS AND METHODS
Female pigs (25-35 kg) were orally premedicated daily with aspirin (100 mg) and ticlopidine (250 mg) for the duration of the study. Under sterile conditions with local anesthesia of the skin provided by 2% lidocaine, an arteriotomy of the left carotid artery was performed, an 8 Fr sheath was inserted, and intraarterial heparin sodium (10,000 IU) was injected. Under fluoroscopic guidance, the coronary artery main branch was selected through an 8 Fr guiding catheter for coronary artery overdilation injury (balloon to artery ratio, 1.3:1) and ICRT. A Ho-166 coated balloon prepared to deliver 20 Gy at a depth of 2 mm from the balloon surface was used for ICRT. The coronary artery main branch in each pig was randomly assigned to either balloon injury (Group I) or balloon injury plus ICRT (Group II). Coronary artery segments were taken from the animals at 0 week (n=8), 4 weeks (n=6) and 8 weeks (n=8) after the intervention. Data in each group denote the relative ratio compared to non-injured coronary artery and are expressed as mean +/- standard error of mean.
RESULTS
The degree of KCl-induced contractile response (g) was not different between the two groups at 0 and 4 weeks, but was significantly decreased in group II compared to group I at 8 weeks (I:1.04+/-0.06, II:0.79+/-0.07, p=0.014). In rings precontracted with prostaglandin F 2alpha (PGF 2alpha), the degree of NO-dependent relaxation (%) induced with substance P was significantly decreased in group II compared to group I at 0 week (I:0.93+/-0.33, II:0.47+/-0.31, p=0.03), but the difference between the two groups was not significant at 4 and 8 weeks. In rings precontracted with PGF 2alpha and LAME in the presence of indomethacin, the degree of EDHF-induced relaxation (%) using substance P was not different between the two groups at 0, 4 and 8 weeks; nor was the degree of sodium nitroprusside-induced endothelium independent relaxation (%) in depolarized conditions with PGF 2alpha.
CONCLUSION
Endothelial function of the porcine coronary artery is only transiently impaired after ICRT using a Ho-166 coated balloon. Therefore this therapy can be used as an effective method to prevent restenosis after percutaneous coronary intervention.