An analysis of cardiopulmonary hemodynamics during hemorrhagic shock in dogs.
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Biomedical subjects
Publications and source records attributed to H Kajihara.
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Changes of secretory activity and structure of the adrenal cortex were observed in dogs subjected to hemorrhagic shock. Blood cortisol and aldosterone levels were rapidly increased after hemorrhage. The cortisol level reached a maximum value about 5 times that of normal 1 h after hemorrhage, while aldosterone levels attained maximum levels showing a 10-fold increase over normal, considerably later (at the end of the impending stage) than the cortisol. Cortisol secretion was quickly depleted at the end of critical stage and terminal stage of normovolemic shock, while the aldosterone secretion remained relatively high. Morphologically, sticking of leukocytes to the sinusoidal wall and accumulation of SER around lipid droplets in the fasciculata and reticularis cells became conspicuous 1 h after hemorrhage. At the end of the impending stage, infiltration of leukocytes occurred in the zona fasciculata and reticularis. Irregular masses of fibrin strands appeared in the sinusoidal space and at large gaps of the sinusoidal wall. Degenerative changes such as aggregation of SER, dilatation of endoplasmic reticulum and edema were observed in the cells of zona fasciculata and reticularis, especially of inner half of the former. At the end of the critical stage, small necrotic foci and hemorrhage with inflammatory infiltration were scattered in the inner half of the zona fasciculata. Degeneration of the cells of zona fasciculata and reticularis became more severe in this period, while the cells of zona glomerulosa remained unchanged. At the terminal stage of normovolemic shock after reinfusion, degeneration and necrosis were remarkable in the cells of zona fasciculata and reticularis, especially of the inner half of the zona fasciculata. Moreover, destruction of cordal structure, hemorrhage and inflammatory infiltration were distinct in the zona fasciculata and reticularis, while the zona glomerulosa was relatively well preserved.
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Eighteen argyrophil cell carcinomas in 101 early gastric carcinomas were explained histologically, ultrastructurally, and immunohistochemically for polypeptides, carcinoembryonic antigen (CEA), lysozyme, and human chorionic gonadotrophin (hCG). Seven of these 18 tumors had gastrin, and two of seven tumors also contained somatostatin. In all of these 18 tumors CEA were demonstrated. Seven had lysozyme and five of seven tumors also contained gastrin; hCG were present in four of the 18 tumors and two of four tumors had gastrin, CA, mucin, and lysozyme simultaneously. Argentaffin cells were found in seven of 18 tumors. Of the above seven tumors containing gastrin, three had argentaffin cells. Ultrastructurally, several types of secretory granules were noted and tumor cells resembling D1- or P cells were present in nine of the 18 tumors. Macroscopically, many of the tumors showed IIc or IIc + III type. Histologically, the 18 tumors consisted of six well differentiated adenocarcinomas and 12 poorly differentiated adenocarcinomas including signet-ring cell carcinoma. These 12 tumors frequently developed in the stomach of young females. In view of our previous investigations, it was suggested that the IIc-type argyrophil cell carcinoma histologically showing poorly differentiated adenocarcinoma may be related to scirrhous carcinoma of the stomach.
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Small granule chromaffin cells (SGC cells) were identified in the adrenal medulla of adult dogs. They were small in size and usually showed a high nucleo-cytoplasmic ratio. Cytoplasmic projections were occasionally observed in some of these cells. They contained a variable number of small secretory granules with diameters ranging from 70 to 300 nm, but mostly from 100 to 200 nm. The densities of the secretory granules were variable, ranging from highly dense to less dense. These adrenal SGC cells were rich in free ribosomes and polysomes, but were relatively poor in other cell organelles. Chromaffin cells which were intermediate in their characteristics (IM cells) between the SGC cells and the typical A and N cells were also identified. These IM cells contained both highly electron dense and less dense granules in various proportions. The IM cells were classified into two subgroups, according to the proportions of adrenaline type granules and noradrenaline type granules. One group resembled A cells (IM-A cells) and the other resembled N cells (IM-N cells). Light microscopic histochemical studies of A cells stained with the ammoniacal silver solution demonstrated that they contained a small number of darkly stained granules. Electron microscopic cytochemistry revealed that the electron dense granuls in the SGC cells, IM cells and A cells reacted positively with both the potassium dichromate solution at pH 4.1 and the ammoniacal silver solution.
Blood catcholamine levels and ultrastructural changes in adrenal medullary cells were followed during the course of oligemic and normovolemic shock in dogs. Blood adrenaline concentration rose promptly after hemorrhage, reaching a maximum that was 10-fold greater than normal during the early period of hemorrhagic hypotension. Thereafter, adrenaline levels gradually declined until the end of the critical stage of hemorrhagic shock when the blood concentration rose to a level 8-fold that of normal. Following the critical stage, and throughout the irreversible stages of shock, adrenaline levels remained near normal. Noradrenaline, which was initially undetectable, first appeared in the impending stage of hemorrhagic hypotension and showed little change during the course of severe hemorrhagic hypotension. Ultrastructural studies demonstrated A-cell degranulation as early as 5 min after initiation of hemorrhage. Degranulation continued throughout the impending stage of hemorrhagic hypotension and was associated with an increasing number of autophagic vacuoles containing empty vesicles. At the end of the critical stage, all A cells showed complete degranulation and degenerative hydropic change. Progression to necrosis rather than arrest or reversal of hydropic change was observed after reinfusion of blood. In contrast to the marked alterations in A cells, most N cells were morphologically unchanged.
The effects of the cardiopulmonary bypass circulation on the cardiac muscle cells were studied electron microscopically. Subendocardial hemorrhage was commonly recognized in both ventricles. However, it appeared earlier and more severely in the right ventricle than in the left ventricle. Clear flocculent areas containing numerous filamentous structures were originated from degradation of myofibrils. Degradation of myofibrils occurred within 1 hour after bypass circulation. Degenerative changes of myocardial cells such as zonal lesions, contraction bands and swelling or condensation of mitochondria appeared in both ventricles. Damages of myocardial cells in right ventricular wall were more severer as compared with those in the left throughout the period of observation.
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Chronic toxicity of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), which had been widely used in Japan as a food additive, was studied in both sexes of ICR/JCL mice by feeding a diet containing AF-2 in a concentration of 0.4% or 0.08%. The experiments confirmed its definite carcinogenicity in the forestomach, with dose dependency; more than 70% of mice fed the higher dose developed tumors, the majority of which were squamous cell carcinomas with metastatic growths, whereas, with a lower dose, fewer tumors occurred, following a longer latent period. In addition, possible leukemogenicity was suggested by a higher incidence in AF-2-fed females (10.8%) over that in control females (3.2%). The development of non-neoplastic lesions in the liver and kidneys, and of amyloidosis in various organs was also observed in some of AF-2-fed mice.
Wistar rats were injected intravenously with cod liver oil emulsion. The lipid droplets ere phagocytized by Kupffer cells and stored in lysosomes. The transformation of these lipid-containing lysosomes into ceroid pigment granules was studied electron-microscopically and cytochemically for a period of 12 weeks after the injection. The lipid droplets enclosed in lysosomes show an increasing and continous condensation from the periphery towards the center due to oxidation and polymerization of unsaturated fatty acids. During the first week almost the total amount of the stored lipids is transformed into an amorphous, highly electron-dense material which disintegrates into cloddy and globular fragments during the following time. The fragments are embedded in a fine granular, slightly electron-dense matrix showing a marked activity of acid phosphatase. The lysosomal structures which contain remnants of condensed oxidized and polymerized lipids are the electron-microscopic equivalent of the granules as seen by light microscopy. These lipids, which have been changed in their molecular structure, cannot be hydrolized by lysosomal enzymes. They remain as an indigestible material, as a waste product in lysosomal residual bodies. Both lipofuscin and ceroid are lysosomal structures containing oxidized and polymerized lipids. The differences between these lipogenous pigments are due to their different formal and causal genesis. Lipofuscin develops in parenchymal and muscle cells by autophagocytosis and by subsequent oxidation and polymerization of segregated membrane lipids. Ceroid is formed in macrophages by heterophagocytosis of unsaturated lipid material which is also oxidized and polymerized.
Wistar rats were injected intravenously with cod liver oil emulsion. The phagocytosis of these lipids by the Kupffer cells as well as the formation of lipid-containing lysosomes were studied electron microscopically within a period of 5 min to 12 hrs. The emulsified lipids are incorporated into the cytoplasm by membrane-vesiculation. The lipid-containing phagocytic vacuoles (lipophagosomes) were transformed into secondary lysosomes (lipophagolysosomes). This change occurs in two phases. Immediately after phagocytosis the lipophagosomes are provided with lysosomal enzymes by fusion with pre-existent lysosomes (dense bodies) of the Kupffer cells. These are mainly the so-called small homogenous dense bodies which are probably primary lysosomes of the type of "storage granules". In the second phase which begins 15-30 min after the injection; the fusion of lipophagosomes with newly produced primary lysosomes within the Golgi apparatus is predominant. Therefore, the enzyme supply of the phagocytic vacuoles does not occur at once but in small amounts during a longer period. The lipids slowly change into an amorphous electron-dense mass 12 hrs after the injection. Obviously, these changes are the first step to the formation of ceroid pigment.
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