Light and electron microscopic studies on rat arterial lesions induced by experimental arterial contraction

Summary Experimental contraction was produced in the rat mesenteric arteries and the arterial segments were studied morphologically. When the rat mesenteric artery was exposed in physiological saline solution at 37° C and 2–3 mg of methoxamine hydrochloride (10 mg/ml) was dripped onto it, intense contraction was observed for about 30 min but elevation in blood pressure was slight. During the contraction, numerous vacuoles were seen in the medial smooth muscle cells of the arterial segments, and these vacuoles were shown electron microscopically to have double unit membranes, indicating that they were formed by herniation of a part of the adjacent smooth muscle cell body. In the arteries 1–6 h after the end of the contraction, cellular, nuclear and vacuolar membranes and myofilaments of the medial muscle cells were partially lost. 12–24 h after the contraction the arteries exhibited necrosis and desquamation of endothelial cells and platelet adhesion. In the media, smooth muscle cells were completely deprived of cell membranes, myofilaments, nuclei, intracytoplasmic organelles other than mitochondria, and vacuolar membranes. The cytoplasm was filled with fine granular and granulo-vesicular material, and fibrin insudation was observed in these severely damaged cells. Arterial contraction may be an important factor in the induction of arterial lesions.     

Diagnosis of cardiac thrombosis in patients with atrial fibrillation in the absence of macroscopically visible thrombi

Summary Cardiac thrombosis due to atrial fibrillation (AF) has been recognized as the most common cause of cerebral embolism. However, sometimes no macroscopic thrombus is found at autopsy in the heart of a victim of this type of cerebral embolism. We investigated morphological changes in the left atrial endocardium of 31 patients (including 21 cases with AF) who had died of cerebral embolism. Rough endocardium (RE) seen macroscopically provided evidence for the existence of atrial thrombosis. The RE that appeared in AF cases was due to a granular and wrinkled appearance of the endocardium associated with oedematous and fibrous thickening. Fibrin-thread deposits were also always distinguishable. Mural thrombi and oedema with neutrophil infiltration in the subendocardium could be seen under the microscope. Small areas of endothelial denudation and thrombotic aggregations were commonly observed by scanning electron microscopy (SEM). These SEM lesions were significantly more frequent in cases with AF than in controls (P< 0.001). The diagnostic success rate for atrial thrombosis among cases with AF increased from 33.3% to 81% when thrombi proven by histological investigation of the areas with RE were added. Left atrial RE may be an anatomically relevant finding for the existence of atrial thrombosis with AF, when the thrombosis cannot be detected upon gross observation at autopsy.     

Scanning and transmission electron microscopic study on the cerebral arterial endothelium of experimentally hypertensive rats fed an atherogenic diet

In order to clarify the roles of hypertension and hypercholesterolemia in atherogenesis, the cerebral arterial endothelium of experimentally hypertensive female rats fed an atherogenic diet were investigated by scanning and transmission electron microscopy. The hypertension was induced by constriction of the bilateral renal arteries. In both hypertensive groups, group I (hypertension + hypercholesterolemia) and group III (hypertension), many endothelial cells covered with numerous microvillous projections were observed. Pinocytotic vesicles and caveolae were also increased in these endothelial cells. On the other hand, in group II loaded with only hypercholesterolemia, microvillous projections on the endothelial cells tended to be increased, but its grade seemed to be lower than those of the hypertensive groups. These findings suggest that hypertension appears to be more effective than hypercholesterolemia in the cause of the increase of microvilli on the endothelial cell surfaces and the increase may be related to increased permeability in the cerebral arteries.     

Derivation of intimal cells appearing in spontaneous healing process of hypertensive arterial lesions.

Light and electron microscopic and autoradiographic studies were made on the process of spontaneous organization of fibrinoid substance deposited in the intima, that is, spontaneous healing of intimal fibrinoid degeneration of the hypertensive rat mesenteric arteries at 8–24 weeks after the constriction of the bilateral renal arteries.The organization of the intimal fibrinoid substance by intimal cells was performed mainly from the luminal side and infrequently from the medial side. Indigenous intimal cells and circulating blood cells were not positively involved in the organization.During the organization of fibrinoid substance, the endothelial cells turned into smooth muscle cell-like cells in situ, and there was a picture suggesting the migration of these smooth muscle cell-like endothelial cells into the intima or their incorporation into the intima by the covering of adjacent endothelial cells. Experiments with intravenous administration of ³H-proline revealed that endothelial cells and intimal and medial smooth muscle cells resembled each other functionally. It can therefore be said that the majority of the cells that participate in the organization of intimal fibrinoid substance are intimal smooth muscle cells derived from endothelial cells, and a part of the cells is derived from medial smooth muscle cells. The cellulofibrous tissue of the intima after the complete organization of intimal fibrinoid substance resulted from the proliferation of the endothelial cellderived intimal smooth muscle cells and from the fiber and ground substance formation by these.     

Morphogenesis of plasmatic arterionecrosis as the cause of hypertensive intracerebral hemorrhage

Summary The morphogenesis of the vascular lesions, which were considered to be the immediate cause of hypertensive intracerebral hemorrhage, was morphologically studied in autopsy cases. The direct cause of the hemorrhage was the rupture of the intracerebral microaneuysms resulted from the plasmatic arterionecrosis. The arterionecrosis was predominantly present in the intracerebral arteries of approximately 150 µ diameter, especially in the external branches of the arteriae corporis striati mediae in the putamen, and characterized by medial smooth muscle cell loss, blood plasma insudation in the intima, histolysis of the internal elastic lamina and intimal collagenous fibers, fibrin deposition (fibrinoid degeneration) in the intima, and luminal dilatation. The morphogenesis of the arterionecrosis was the development of histolysis as well as fibrinoid degeneration caused by blood plasma insudation in the wall of the intracerebral arteries with preceding necrosis and loss of medial smooth muscle cells and subsequent fibrous intimal thickening with dilated lumina. Intracerebral microaneurysms were also formed by the plasmatic arterionecrosis in a narrow sense, in which histolysis due to blood plasma insudation had occurred, but fibrin (fibrinoid substance) deposition in the intima had not yet arisen.     

MORPHOGENESIS OF ARTERIOSCLEROSIS

The basic process in the morphogenesis of arteriosclerosis consists of proliferation and insudation in the intima, and varied combinations of these two processes produce various types of arteriosclerotic lesions.
The morphogenesis of atherosclerosis is considered to be as follows: Atheroma is formed by the infiltration of blood plasma lipids into the intima of the large and medium-sized arteries having cellulofibrous intimal thickening, which grows with age. As the result, proliferation advances especially in the upper layer of the intima. There were two types of atheroma formation.
Arteriosclerosis of the small arteries and arterioles is produced by various combinations of insudation and proliferation in the small arteries and arterioles where the intimal thickening does not occur with age, or only to a slight degree, if any.
In order to elucidate the mechanism of the proliferation and insudation in the intima, animal experiments were carried out. On the basis of the experimental results, possible causes of the proliferation (cellulofibrous intimal thickening) and the insudation (blood plasma infiltration) were discussed. ACTA PATH. JAP. 18 :75–82, 1968.