Morphometry of air-drying-induced arteriosclerosis in rat carotid artery. Effect of air-flow rate.

Abstract

Arteriosclerosis in the Wistar rat carotid artery was induced by air drying of the endothelium, a procedure that caused media necrosis. We describe a number of technical modifications that facilitate the procedure and minimize damage to the vessel wall (i.e., media necrosis). A morphometric study of vessel wall changes induced by endothelial denudation at various air-flow rates showed that necrosis of the inner medial layer and lesion size and position were constant at all flow rates used (=s 28 ml/min). The extent of necrosis of the outer medial layers, the endothelial repair, and the shape of the lesions varied with the air-flow rate used. Since at an air-flow rate of 28 ml/min medial necrosis was minimal and myointimal lesion development was as extensive as at higher flow rates, we consider this air-flow rate to be optimal for this model of experimental arteriosclerosis. We hypothesize that the shape of the myointimal lesion is determined by the timespan of endothelial denudation and by the availability of smooth muscle cells in necrotic and normal media. Furthermore, the proliferation of the smooth muscle cells and their migration into the intima is probably dominant over the repopulation of the media by these cells. (Arteriosclerosis 3:441-451, September/October 1983) T he formation of arteriosclerotic, fibromuscularelastic intimal thickening following experimental endothelial denudation has been well documented in a number of animal models. 1 " 4 In rat arteries mechanical injury, 5 air-drying, 6 and balloon catheterization 78 have been shown to remove the endothelium and to cause myointimal thickening. Although these experiments were aimed at specificially causing endothelial injury, the underlying media was often affected as well.8 " 10 Fishman et al. 6 and Clowes et al. 11used the air-drying technique in the rat and claimed that injury, at least at the time of denudation, was confined to the endothelium. This apparent selectivity led us to choose the air-drying model for a study of the effect of experimental conditions on lesion development.In our study however, we found that this injury was not as selective as in other studies; 6 media necrosis (disappearance of smooth muscle cells) occurred in certain areas of the vessel wall. Furthermore, a different intimal thickening pattern was observed. Preliminary studies indicated that the velocity of infused air was important. To find the optimal conditions, we performed the air-drying method by lowering the airflow rate in steps of approximately 5 ml/min down to the lower limit of lesion induction. The air-drying technique of Fishman et al. 6 was modified, thereby facilitating surgery, avoiding mechanical injury at air inflow and outflow holes, and minimizing media necrosis.In this paper we shall present a univariate quantitative analysis of the changes in vessel wall morphology that we found when applying diminished air-flow rates to denude the artery. Special attention will be paid to parameters describing the resulting myointimal lesions, endothelial repai...

Replication of smooth muscle cells in vascular disease.

“…Injury to the endothelium has been caused experimentally by a variety of traumas (Baumgartner and Studer, 1966;Veress et al, 1969;Stemerman and Ross, 1972;Bjorkerud and Bondjers, 1973;Knieriem et al, 1973;Fishman et al, 1975;Schwartz et al, 1975;van Pelt-Verkuil et al, 1983). Small wounds heal without stimulation of smooth muscle replication (Reidy and Schwartz, 1984).…”

Effect of Turmerin on Endothelial Denudation by Air Drying

“…The endothelium was washed at the proximal and distal ends of the artery with phosphate buffered saline (PBS) using a tuberculin syringe. The artery was treated with compressed air at 28 ml/min for 5 min [12]. It was then flushed with PBS and clipped.…”

Defibrinogenation by Arvin Reduces Air-Drying-lnduced Arteriosclerosis in Rat Carotid Artery

“…Myointimal thickening was induced in the left carotid artery of 36 Nembutal anaesthesized (60 mg/kg i.p.) male Wistar rats by a modifica tion of Fishman's (13) air-drying method, as described in detail elsewhere (14,15). In brief: 20 mm segments of the left carotid artery were isolated with aneurysma clips (20 g/cm2), rinsed with saline, and air-dried at an air flow rate of 28 ml/min for 4 min.…”

“…Distances along the longitudinal vessel axis (in mm) were calculated taking the entrance point of air as origin, after correction for vessel segment length changes during fixation and embedding (compare ref. 14).…”

“…The resulting graph was read by a digitizer tablet, and the area under curve was calculated as a measure of lesion volume (compare ref. 14).…”