Arterial Histology in Amputated Limbs with Chronic Limb-Threatening Ischemia and Cadaver Limbs

Abstract

ObjectiveThe study objectives were to 1) elucidate the histopathological and structural alterations in the femoral to popliteal arteries and tibial or more distal arteries in patients with chronic limb-threatening ischemia through detailed histomorphological and histopathological examinations of the lower limb arteries in the amputated limbs; and 2) elucidate the basic structure of the entire lower extremity, from the external iliac artery to the digital artery, based on histomorphological examinations of cadaver limbs. MethodsWe examined the histopathology and histomorphology of lower limb arteries harvested from 22 amputated limbs and that from 11 cadavers without lower limb issues. Sixty-three sections from the amputated limbs were categorized into femoropopliteal, tibial, and distal segments. Five hundred ten sections (from the external iliac artery to the digital artery) from the cadavers were categorized as femoropopliteal segments, tibial and distal segments, and others. The modified American Heart Association classification was used for the histopathological analysis, and the advanced lesion was defined as the presence of progressive atherosclerotic lesion. In the histomorphological analyses, we calculated %stenosis, %medial area as the medial area divided by the area within the external elastic lamina × 100, and %intimal area as the intimal area divided by the area within the external elastic lamina × 100. ResultsIn amputated limbs, advanced lesions and calcification in the medial area were more prevalent in the femoropopliteal segments than in the tibial and distal segments (advanced lesion: 8/10 vs. 18/42, p=0.048; calcification: 10/10 vs. 28/42, p=0.037), while %stenosis and prevalence of luminal thrombi were comparable. Significant inverse correlations were noted between %medial area and external elastic lamina diameter in both amputated (r=-0.641, p<0.001) and cadaver limbs (r=-0.775, p<0.001). In the femoropopliteal segments of the amputated limbs, luminal stenosis was solely caused by intimal lesions, whereas in the tibial and distal segments, medial area thickening contributed to luminal stenosis when intimal lesions were less pronounced. When the external elastic lamina diameter was entered as a covariate, the medial area of the 178 cadaver tibial and distal segments with minimal intimal lesions (<40% intimal area) was significantly greater when >75% stenosis was present in the femoropopliteal segments (p<0.001). ConclusionAdvanced lesions in the tibial and distal segments are less prevalent compared to the femoropopliteal segments. Medial area thickening may contribute to luminal stenosis in the tibial and distal segments when intimal lesions were less pronounced, which may be secondary to a significant proximal occlusive lesion.