984-29 Modulation of s-Homocysteine Associated with Intimal Thickening After Balloon Angioplasty Injury of the Rabbit Iliac Artery

Abstract

Hyperhomocysteinemia is associated with arterial disease. Elevated levels of s-homocystein (Hcy) have been suggested to cause intimal injury and smooth muscle cell recruitment. Since a similar vessel wall response is also seen in restenotic lesions after balloon angioplasty, we studied the effects of moderate reduction and elevation of s-Hcy levels on the potentiation of arterial wall thickening after balloon injury in the iliac artery of rabbits. 16 female Chinchilla (Chbb:CH) rabbits were randomized to receive either Hcy-lowering therapy with pryridoxin, cobalamin, folic acid and Betain (group 1, weight 3.9 kg) or Hcy-increasing therapy with methionin (group 2, weight 3.8 kg, p = NS). After one week transcatheter balloon angioplasty was performed via right carotidotomy using an oversized (3.0 mm) balloon catheter. Angiography was performed after angioplasty and after 9 weeks, when the rabbits were sacrified and perfusion-fixed. Injury response was measured by histomorphometry. Pre-treatment s-HcY-levels were 17.2 + 6.9 vs 16.7 + 5.3 mmol/l for group 1 and 2 (p = NS), at the time of angioplasty 13.5 + 2.9 vs 20.0 + 7.0 (p < 0.05) and these differences remained throughout the study. Histomorphometry showed intima/media area ratio 0.44 + 0.17 vs 0.73 + 0.24 (p = 0.03), intima/media thickness ratio 1.11 + 0.93 vs 2.00 + 2.79 (p = 0.03) and absolute intima thickness 0.11 + 0.01 vs 0.22 ± 0.04 mm (p = 0.03) for group 1 and 2 resp. Angiographic videodensitometry was consistent with the histomorphometric findings. Hyperhomocysteinemia contributes to intimal thickening in the rabbit iliac artery after balloon angioplasty injury.