THE WATANABE HERITABLE HYPERLIPIDEMIC RABBIT AS A SUITABLE EXPERIMENTAL-MODEL TO STUDY DIFFERENCES IN TISSUE-RESPONSE BETWEEN INTIMAL AND MEDIAL INJURY AFTER BALLOON ANGIOPLASTY

The study evaluates whether the Watanabe heritable hyperlipidemic (WHH L) rabbit is an adequate model to study mechanisms that underlie diffe rences in tissue response after postangioplasty injury. Postangioplast y studies of human coronary arteries have revealed that healing and re stenotic processes differ depending on whether the laceration is limit ed to the atherosclerotic plaque or whether injury extends into the me dia. Forty-five homozygous WHHL rabbits underwent percutaneous translu minal angioplasty of the left subclavian artery. The inflated arterial segment was studied histologically at 3, 7, 14, 28, and 56 days, usin g conventional and immunohistochemical techniques to identify macropha ges, smooth muscle cell (SMC) phenotypes, and cell proliferation. Elec tron microscopy was done to study reendothelialization. There were mar ked differences in response between those segments with medial injury and those with injury limited to the atherosclerotic plaque tissues. T he latter category shows a distinct retardation in redifferentiation o f SMCs, confirming previous observations in human coronary arteries. I n these segments, moreover. cell proliferation occurred mainly in macr ophages and spindle cells. Medial injury showed a more florid fibrocel lular response, as in human coronary arteries, with cell proliferation initially confined to areas with dedifferentiated SMCs in the preexis tent media and, once neointimal tissue was formed, among spindle cells also. The similarities with the repair processes encountered in posta ngioplasty human coronary arteries suggest that the WHHL rabbit is an adequate model to study differences in the response related to differe nt types of angioplasty injury.