COMBINATION OF VITAMIN-C AND VITAMIN-E ALTERS THE RESPONSE TO CORONARY BALLOON INJURY IN THE PIG

Restenosis is the major limitation of the long-term success of percuta neous transluminal coronary angioplasty. The process of restenosis inv olves repair of vascular injury and remodeling of vessel architecture. Therapeutic interventions that improve vascular function may therefor e be beneficial in the treatment of restenosis. Antioxidants such as p robucol and vitamins C and E have proved effective in improving endoth elial function in hypercholesterolemia, inhibiting lipid accumulation in animal models of atherosclerosis, and decreasing cardiovascular mor tality in humans. Forty-two female domestic swine were divided into fo ur study groups: control (n=12); vitamin C (500 mg/d, group C, n=9); v itamin E (1000 U/d, group E, n=10); and vitamins C and E (500 mg/d + 1 000 U/d, group C + E, n=11) before oversized balloon injury of the lef t anterior descending and circumflex coronary arteries. Vitamins were administered 7 days before balloon injury and continued until the swin e were killed 14 days after injury. Significant differences in morphom etric parameters were present only in group C + E, with increases in v essel and lumen area in the segment with maximal injury. Although ther e was no decrease in intima area or in maximal intima thickness, the r atio of intima area to vessel area was significantly reduced, consiste nt with a positive effect in group C + E. Graphic analysis of the rela tionship between initial vessel injury (using internal elastic lamina fracture length/lumen perimeter) and vessel response to injury (using intima area/vessel area) for all segments showed improved indices for group C + E (P<.005). The beneficial effect of vitamins correlated wit h changes in lipid redox state. Low-density lipoprotein (LDL) thiobarb ituric acid-reactive substances showed an approximate to 70% decrease in all treatment groups, and the lag phase for LDL-conjugated diene fo rmation was significantly increased, with group C + E>group E>group C. The combination of vitamins C and E improved vascular response to inj ury because of an apparent beneficial effect on vascular remodeling. T he fact that the combination of vitamins C + E was better than vitamin E or vitamin C alone is consistent with the ability of vitamin C to i mprove the antioxidant effect of vitamin E, suggesting that the improv ed vessel response was due to a change in redox state. This study sugg ests an important role for oxygen radicals in the vascular response to injury and suggests that vascular remodeling and intimal proliferatio n are important to the restenotic process.