Genju Ooneda

Morphogenesis of plasmatic arterionecrosis as the cause of hypertensive intracerebral hemorrhage

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.

ELECTRON MICROSCOPIC STUDIES ON THE MORPHOGENESIS OF FIBRINOID DEGENERATION IN THE MESENTERIC ARTERIES OF HYPERTENSIVE RATS.

† Department of Pathology, School of Medicine, Gunma University, Maebashi, Japan. The direct cause of apoplectic cerebral hemorrhage (hypertensive intracerebral massive hemorrhage) is the so-called angionecrosis of intracerebral arteries. It is, both histologically and histochemically, very similar to fibrinoid degeneration in the systemic arteries of hypertensive rats which is induced by surgical constriction of the bilateral renal arteries (Ooneda and associates’; Takatama2) . The fibrinoid degeration is observed not only in hypertensive, allergic and collagen diseases, but also in other miscellaneous pathologic conditions (Matsuyama and co-workers3) . As to the morphogenesis of the degeneration, which is characterized by the presence of fibrinoid substance in vascular

Smooth Muscle Cells in the Development of Plasmatic Arterionecrosis, Arteriosclerosis, and Arterial Contraction

Plasmatic arterionecrosis, the causative lesion of hypertensive cerebral hemorrhage, follows upon medial muscle cell necrosis. The development of medial muscle cell necrosis, the earliest cerebral arterial change seen in hypertensive rats, was inhibited when these animals were fed a cholesterol and lard-supplemented diet. Insudation of fibrin was noted in the arterial intima of hypertensive rats with bilaterally constricted renal arteries. Removal of the constriction induced a fall in the elevated blood pressure and an increase of intimal muscle cells. These were responsible for the dissolution of the deposited fibrin, leading to arteriosclerosis. These myointimal cells may originate from the endothelium. Arterial contraction caused by methoxamine hydrochloride often induced the intrusion of one medial muscle cell into another and increased endothelial permeability. 12-24 h after contraction, the arterial segments showed medial muscle cell necrosis, endothelial desquamation with platelet adhesion, and blood plasma infiltration.

Increased permeability of the arteries in hypertensive rats: An electron microscopic study

Abstract Fibrinoid degeneration of the mesenteric arteries in hypertensive rats with bilaterally constricted renal arteries could be ascribed to insudation of blood plasma constituents, especially fibrinogen, into the arterial wall. We investigated electron microscopically what part of the arterial endothelium the blood plasma would pass through, using ferritin or carbon as a tracer. Ferritin (50–100 A), which was given intravenously to the hypertensive rats, was observed in pinocytotic vesicles and cytoplasm of endothelial cells, in the intercellular space of endothelium, and in the subendothelial space of the mesenteric arteries, whereas intravenously injected carbon particles (200–500 rA) were not found in the pinocytotic vesicles and cytoplasm of endothelial cells, but in the opened intercellular space of endothelium and in the subendothelial space. It was, therefore, considered that there were three pathways of blood plasma insudation into the arterial wall of hypertensive rats, that is, intercellular, transcellular, and transcellular through pinocytotic vesicles. The transcellular permeability seemed to be utilized mainly for permeation of small molecular substances such as albumin, the intercellular permeability in the state of unopened intercellular junction for insudation of fibrinogen, globulin, and albumin, and that in the state of opened junction for insudation of blood cells, fibrinogen, globulin, and albumin. Filaments (50–70 A thick) were increased in endothelial cells of the mesenteric arteries of hyptertensive rats, and ovoid dense areas were observed there also. These filaments were considered to be involved in the contraction of endothelial cells and subsequently in the opening of the junctions between endothelial cells.

Cerebral arterial lesions in experimental hypertensive rats: Electron microscopic study of middle cerebral arteries

Abstract In the branches of the cerebral arteries of hypertensive rats, medial damage preceded intimal fibrinoid degeneration. The hypertensive medial damage was characterized by degeneration, necrosis, and disappearance of the smooth muscle cells. The lesions of the medial smooth muscle cells were characterized by focal cytoplasmic necrosis and formation of dense granular, vesicular, and tubular cell debris in the necrotic areas. Furthermore, coagulation necrosis, liquefaction necrosis, and edematous change of the cytoplasm were observed. The cytoplasm bordering on the focal cytoplasmic necrosis in the peripheral areas of the smooth muscle cells produced a new cytodemarcating membrane. Around damaged smooth muscle cell was observed lamellar or reticular increase of basement membrane. This may have resulted from the repetition of necrosis and disappearance of peripheral cytoplasm of the smooth muscle cells and re-formation of the basement membrane.

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

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

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.

Topographical study on arteriosclerotic lesions at the bifurcations of human cerebral arteries

SummaryWe have studied the topographical distribution of arteriosclerotic lesions at the bifurcation of the internal carotid-anterior cerebral-middle cerebral arteries (internal carotid bifurcation) and of the middle cerebral artery-first temporal branch (first bifurcation of M.C.A.) in humans. The arteriosclerotic lesions showed a distinct pattern with a high incidence on the outer walls of the daughter vessels and at the inner curvatures in the bifurcations where wall shear stress was believed to be relatively low. However, there were differences in the distribution of the lesions between the internal carotid bifurcations and the first bifurcations of M.C.A.. The former are considered to be three-dimensionally unsymmetrical and curved, and the latter symmetrical and straight. The present study suggests that lower shear stress is of considerable importance in both the initiation and localization of arteriosclerotic lesions, and that study of the three-dimensional blood vessel architecture and blood flow patterns needs to be done to clarify the role of hemodynamic forces in atherogenesis.

An electron microscopic study of plasmatic arterionecrosis in the human cerebral arteries

An electron microscopic study of the intracerebral arteries from 9 hypertensive cases was performed in order to elucidate the morphogenesis of the plasmatic arterionecrosis which was considered to be the direct cause of hypertensive intracerebral hemorrhage. In the preceding stage of the arterial lesions, marked necrosis of medial smooth muscle cells and increase of basement membrane-like substance in the intima and media were observed. The lumina of these arteries were slightly dilated. The dilatation and hemodynamic factors were supposed to cause endothelial injury resulting in blood plasma insudation into the intima through the opened spaces between endothelial cells. The insudated blood plasma dispersed and dissolved the basement membrane-like substance, collagen and elastic fibers in the arterial wall, leading to the development of the plasmatic arterionecrosis.

Age-induced changes of cerebral arteries in rats

Age-related changes of the anterior cerebral arteries of Wistar rats were studied by electron microscope. Medial smooth muscle cells (SMC) in the young rats often made membranous contact. Myo-endothelial junction was also observed. In the 4-week-old arteries, development of cerebral arteries was almost complete. In the 3-month-old arteries, necrotic changes of the SMC appeared in the media. In aging rats, medial SMC necrosis was characteristically observed in the outer media. The outer surface of the SMC showed irregular shape and necrotic substance derived from the SMC was increased with advancing age. Increase of collagen fibers was seen only in the outer media and the adventitia.