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R S McCuskey

Publications and source records attributed to R S McCuskey.

98 records · Page 6Linked to original sources
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In vivo microscopy of the exocrine pancreas.

Light microscopic studies of the living acinar pancreas, although limited in number, have revealed valuable information concerning dynamic aspects of microvascular and parenchymal structure and function. For example, it has been found that: 1) the living organ in anesthetized animals can be imaged with a resolution approaching the limit of the light microscope; 2) blood flow through individual capillaries in the exocrine pancreas is intermittent; 3) blood flow through these capillaries is regulated locally by smooth muscle precapillary sphincters and within individual capillaries by endothelial cells which are spontaneously contractile as well as responsive to vasoactive substances; and 4) the formation and release of zymogen granules occurs within 45-90 minutes in acinar cells stimulated with pancreozymin. This paper reviews these studies and some of the methods used to obtain them.

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Hepatic microvascular regulatory mechanisms. II. Cholinergic mechanisms.

Several cholinergic agonists and their antagonists were administered topically at various concentrations (10(-10) to 10(-4) gm per ml) to the livers of anesthetized Sprague-Dawley rats. Changes in the microvasculature were measured for a period of 15 min using in vivo microscopic methods. The influence of cholinergic agonists on hepatic mast cells was determined by histochemical methods. Cholinergic agonists elicited constriction of portal venules, sinusoids, and terminal hepatic (central) venules accompanied within 5 to 20 sec by the adherence of platelets and leukocytes to the endothelial lining of these vessels. These responses were not observed in hepatic arterioles or hepatic (sublobular) venules. However, the responses drastically altered cellular flow through all segments of the microvasculature. The drugs were effective in the following ranking: bethanechol greater than pilocarpine greater than carbachol. Vascular responses were not antagonized by atropine; phentolamine modified the constrictor response of portal venules but of no other microvascular segment. These results suggest that the responses were not mediated by cholinergic (muscarinic) receptors and that the constriction of portal venules was caused by the chemical activation of alpha-adrenergic receptors. Histochemical methods revealed that pilocarpine and bethanechol also elicited a significant decrease in the number of visible mast cells suggestive of degranulation and the release of serotonin, histamine, and other polyanions (e.g., heparin) from these cells. Release occurred within the same period of time as the microvascular alterations (15 min.). These data provide additional evidence that mast cell constituents and adrenergic mechanisms are involved in hepatic cholinergic mechanisms.

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In vivo and electron microscopic observations of the hepatic microvasculature in the rat following portacaval anastomosis.

The livers of rats subjected to end-to-side portacaval anastomoses were studied 3 to 5 months postoperatively by in vivo and electron microscopy. Compared with sham-operated controls, the livers of portacaval anastomoses animals contained dilated, tortuous networks of sinusoids. The velocity of blood flow in these vessels tended to be slower and more variable than controls, but always progressed toward the hepatic venules. Blood entered the sinusoids from portal venules and from arteriosinus twigs which terminated in the initial segments of some of the sinusoids at the periphery of the lobule. Together, the arteriosinus twigs and the short, initial segments of these sinusoids formed functional arterioportal anastomoses. These, in combination with the lack of portal venous flow, resulted in retrograde blood flow in portal venules. Nevertheless, blood still flowed from these portal venules into the sinusoids unless the sinusoid was fed by an arteriosinus twig. In addition to these microcirculatory alterations, the number of Kupffer cells that phagocytized latex particles was less in the animals with portacaval anastomoses, as was the number of particles ingested by these cells. Scanning and transmission electron microscopy confirmed the paucity of Kupffer cells. Those seen appeared inactive since they were flattened, exhibited few microplicae and filopodia and contained few latex particles. The endothelial cells of the sinusoid lining were perforated by increased numbers of large fenestrate which may be a reflection of elevated intrasinusoid pressures generated by the expanded arterialization of the sinusoid bed. The observed dilated sinusoid network interspersed by narrowed plates of hepatocytes is also consistent with this hypothesis. Finally, scattered nodular foci were observed which contained enlarged hepatocytes, narrow sinusoids, active Kupffer cells, and more normal rates of blood flow. Such sites may represent attempts by the liver to regenerate its normal architecture.

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PubMedDate not supplied

Phagocytosis, an unrecognized property of murine endothelial liver cells.

Impairment of the phagocytic capacities of Kupffer cells, as is found in Frog Virus 3 hepatitis of mice, allows the endothelial liver cells to take up intravenously inoculated latex particles of 1.0 micron diameter. In vitro experiments with cultivated endothelial cells isolated by collagenase perfusion of the liver and purified by centrifugal elutriation demonstrate that uptake occurs via a typical mechanism of phagocytosis involving pseudopodia. Ingestion of latex is inhibited by incubation of the cells at 4 degrees C and by treatment with cytochalasin B, whereas colchicine has no effect. These results demonstrate that: the Kupffer cells are not the only cells of the hepatic sinusoid capable of phagocytosis; and under conditions where the phagocytosis in Kupffer cells is impaired, the endothelial cells may participate in the clearance of large particles from the blood.

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PubMedDate not supplied

Kupffer cell function in host defense.

High-resolution in vivo microscopic methods have been used to explore the responses to endotoxin of Kupffer cells in the livers of anesthetized mice, rats, hamsters, and guinea pigs under a variety of experimental conditions. These include studies of normal animals as well as of animals sensitized or tolerant to endotoxin, C3H/HeJ mice with a low response to endotoxin, mice rendered septic by cecal ligation and puncture, mice with Kupffer cells selectively destroyed by frog virus 3, and rats with portacaval shunts. The functional state of Kupffer cells was evaluated by measuring both the number of these cells per microscopic field that phagocytosed 1.0-micron latex particles and the rate at which individual Kupffer cells phagocytosed single latex particles. The intrahepatic density and level of activation of Kupffer cells were found to play a role in determining endotoxin sensitivity and to be involved, in conjunction with endotoxin, in the development of tolerance. All of these studies support the concept of a central role for Kupffer cells in host defense mechanisms and of the possible modulation and of this role by gut-derived endotoxins contained in the portal blood.

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