We investigated the effect of an anti-arteriosclerotic agent Elastase (Elaszym®) on coronary arteriosclerosis in rabbits by histochemical observation and quantitative analysis of smooth muscle cell (SMC), elastin (EL), collagen (CL), acid mucopolysaccharides (AMPS) and glycoprotein (GP) in coronary media. The subjects were male 38 month-old Japanese White Rabbits. Of the 23 rabbits studied, 8 were healthy (H group), 9 had coronary arteriosclerosis (S group), and 6 had coronary arteriosclerosis and were administered with the Elaszym (A group). Arteriosclerotic rabbits were prepared by the combination of 3 method, the hypoxic method in which N2 gas inhalation was given to the rabbits daily for 2 consecutive weeks, the injury method in which intramuscular administration of norepinephrine was given for 22 weeks, and the preparation method of coronary intimal lesion in which oral administration of cholesterol (0.5g/day) was given for 22 weeks. The rabbits in A group were given Elastase at the dose of 6 cap/day (10.800 EU) once a day for 22 consecutive weeks starting simultaneously with the load of above mentioned preparation. On completion of the treatment, all the rabbits were terminated and histologic specimen was picked up from the left coronary tissue with myocardium for subsequent observation and quantitative analysis of above mentioned 5 components in proximal coronary artery by microspectrophotometry. Comparisons were made of histologic image and quantity of each component among these 3 groups, furthermore, each group was comprehensively evaluated for its characteristics by the principal component analysis of change in 5 components.
S group demonstrated decrease in SMC because of hypertrophy, swelling, atrophy, necrosis and extinction. Uniform distribution of EL and CL was observed due to swelling decomposition and local abnormal hyperplasia. More active hyperplasia was recognized in AMPS and GP than in the case of EL or CL as a repair mechanism of damage. There appeared stratified delamination of elastic fibers from internal elastic membrane and it caused hypertrophy of intima as well as diminution on plasmotomy of elastic membrane. In A group, every kind of impairment as observed in S group was suppressed and the basic architecture of coronary artery was well maintained. The values of SMC, EL, CL, AMPS, GP were 65.4, 9.6, 25.7, 14.4, 22.8%E respectively in H group, 46.7, 12.2, 35.6, 20.2, 31.6%E respectively in S group, and 62.6, 11.3, 29.1, 11.8, 26.2%E respectively in A group. In S group, significant decrease was observed in SMC value with significant increase in EL, CL, AMPS and GP compared with those in H group. In A group, these changes were significantly suppressed compared with those in S group. Individual scores in the 1st and 2nd components were plotted in the two-dimensional coodinates for each case. The dots of H group were distributed in the left narrow range while the dots of S group were distributed in the right wide range of the coodinates. Thus these 2 groups showed quite different architectural characteristics of artery. However, the distribution of A group was observed in the left narrow range similarly to that of H group. Therefore, it can be considered that the rabbits in A group have architectural characteristics closely akin to those in H group. These findings suggests an inhibitory effect of Elaszym on development of coronary arteriosclerosis.
