The effect of ethane- l-hydroxy-1,1-diphosphonate (EHDP) on necrosis of atherosclerotic lesions

Abstract

Administration of ethane-l-hydroxy-1,1-diphosphonate (EHDP) to swine with pre-established atherosclerosis resulted in lower lesion calcium concentration, smaller lesions and a decrease in the area of lesions involved in necrosis. Atherosclerosis was developed in Yorkshire swine by balloon catheter-injury to the abdominal aorta, followed by a high cholesterol-high lipid (HL) diet for 4 months. The administration of EHDP (20 mg/kg/day) was begun after these 4 months and continued for 5 additional months along with the atherogenic diet. Other swine were ballooned and fed HL diet for nine months. Morphometric analysis showed that the extent of lesions, expressed as ratio of intima to media was significantly less ( P < 0.05) in the EHDP-treated HL swine, compared to the HL diet-only group. The ratio of lesion areas showing lipid-rich necrotic debris to the area of media was also significantly smaller ( P < 0.05). Biochemical analysis showed that the lesion from the HL drug-treated group contained significantly less ( P < 0.05) calcium compared to that from the HL diet only. Finally, there was significant correlation between average lesion area and average lesion calcium concentration ( P < 0.02) for both groups. While the effect of EHDP on lesion size and calcium concentration has been previously reported for various species such as rabbit and monkey, this study is believed to be the first where a beneficial effect of EHDP on one of the most serious complications of atherogenesis — necrosis — has been documented. The mechanisms by which EHDP may affect necrosis are discussed.