Effects of preinjury administration of corticosteroids on pseudointimal hyperplasia and cytokine response in a rat model of balloon aortic injury.
Restenosis occurs in approximately one-third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin-6 (IL-6), IL-10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL-6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL-10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL-6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.
Nagasaki
Kazuhito
K
Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku 160-8582, Tokyo, Japan.
Matsumoto
Kenji
K
Kaneda
Munehisa
M
Shintani
Tsunehiro
T
Shibutani
Shintaro
S
Murayama
Takaya
T
Wakabayashi
Go
G
Shimazu
Motohide
M
Mukai
Makio
M
Kitajima
Masaki
M
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000293:injuries*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000008:administration & dosage*; D006965:Hyperplasia / Q000097:blood / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000473:pathology*
D005938:Glucocorticoids; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D016753:Interleukin-10; D008775:Methylprednisolone