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J.Jpn. Surg. Soc.. 62(3): 291-313, 1961


EXPERIMENTAL STUDIES ON HISTAMIN, HISTAMINASE AND HISTIDINE DECARBOXYLASE IN ILEUS

Department of Surgery, Nihon Medical School (Director: Prof. Saburo MATSUKURA)

Rintaro MORIYA

In the previous reports on experimental investigations on the fluctuations of histamin in detail during ileus, Matsukura and Terakado stated their conclusions as follows:
1) During ileus the histamin content or blood shows no change whatever as compared under normal conditions.
2) Although the histamin content of ascitic fluid shows little difference from that of blood, in cases of marked necrosis developing in the intestine during ileus a slight increase can be demonstrated.
3) The quantity of histamin may be greatly increased in the intestinal contents during ileus in a certain number of cases, but others may show no significant variations whatever .
4) The histamin content of the intestinal tissue may be slightly increased both in the portion above and below the obstruction in some, while in other no significant changes whatever are demonstrable.
5) The liver and lung tissues show no changes in their histamin content, just as in normal conditions.
6) Even when a large amount of histamin is introduced into the lumen of obstructed intestinal canal, no increase whatever can be demonstrated in the histamin content in the blood of femoral vein or portal vein throughout the course of ileus as compered with normal conditions.
From the results above summarized, Matsukura and Terakado concluded that histamin is not a blood constituent concerned in ileus. However, recently McIntire and others have offered some critical comments on this conclusion, for the reason that the quantitative values for histamin obtained by the use of such complicated methods as those of the authors and of Yokoyama are not entirely without errors. The present author, therefore, has re-examined the results r eported by Matsukura and Terakado concerning the fluctuation of histamin during the course of ileus by employing the quantitative procedure of McIntire, namely, the cotton acid succinate method. The results so obtained may be summarized as follows:
1) In ileus the amount of histamin in plasma shows no increase during its entire course.
2) The presence of histamin can be demonstrated in minute quantities in the ascitic fluid only during the terminal stage of ileus.
3) Greatly increased amounts of histamin become demonstrable for the first time in the contents of a closed loop of intestione only during the terminal stage of ileus.
(4) (i.) Of the intestinal tissue, the colon normally shows low values of the histamin content in contrast to those of the ileum, in which the values become greater as the location chosen for determination is higher.
(ii.) However, during the course of ileus, the amount of histamin shows little changes in the intestinal tissues including the portions above or below the obstruction as well as the closed loop up until the 6th hour after the establishment of ileus. The change begins to appear at about the 9th hour, gradually increasing so that in the terminal stage the values may reach 1.5-3 times those obtained under normal conditions.
(5) (i.) Normally the histamin content of the liver tissue shows values 3-6 times those of the intestinal tissue.
(ii.) On the contrary, the histamin content of the liver tissue changes but little during ileus.
These results are in rough agreement with those previously obtained by Matsukura and Terakado, and reaffirm the fact that histamin is not the active substance concerned in ileus, as elucidated by the use of a new quantitavive metood of McIntire.
A new question arises at this point, however, in regard to the retention of the increased amount of histamin in the intestinal canal under obstruction and in its contents, with no evidence of any amount being transfered into the blood. When this mechanism is clarified, then the failure of histamin increase in the blood would naturally be explained.
As a means of analysing this mechanism, the author went further by determining the flucturations of histaminase, a histamin-deposing enzyme, and also of histidin-decarboxylase, a histamin-synthesizing enzyme, in certain tissues including the plasma, intestinal canal and liver. The results of observation are as follows:
I. (1) In ileus the activity values of plasma histaminase show a tendency to slight decrease, but these changes are all within the normal range.
(2) (i.) The activity values of histaminase in the intestinal tissue under normal conditions are at surprisingly high levels, usually 15- 20 times those seen in the liver tisse.
(ii.) While these values are high in the upper and middle portions of the ileum, they are low in the lower portion and in the colon.
(iii.) In ileus the histaminase activity values in the intestinal tissue show little changes in the portions above and below the obstruction, but they begin to decrease in the closed loop during the terminal stage. Even at this stage the activity levels are 3-5 times higher than those of the normal liver tissue.
(3) The histaminase activity values in the liver tissue during ileus tend to decrease slightly during the terminal stage, although these changes are still within the normal limits.
II. (1) Practically no changes are seen in the values of plasma histidin decarboxylase activity during ileus.
(2) (i.) The activity values of histidin decarboxylase in the intestinal tissue under normal conditions show about the same level in the upper, middle and lower portions of the ileum.
(ii.) Likewise during ileus the activity levels of histidin decarboxylase in the intestinal tissue are without much alteration in the portions both above and below the point of obstruction as well as in the closed loop.
(3) (i.) Normally the histidin decarboxylase activity of the liver tissue is at a slightly lower level as compared with that of the intestinal tissue.
(ii.) During ileus the histidin decarboxylase activity of the liver tissue shows a tendency to decrease slightly, although the levels are within the normal range.
To summarize the results obtained from the analyses of histaminase and histidindecarboxylase, the point of great significance lies in the discovery of great amounts of these enzymes in the intestinal tissue, approximately 15- 20 times those found in the liver tissue. This finding explains why histamin, formed so abundantly in the intestinal canal, fails to migrate into the blood, because of the presence of the enzyme in quantities sufficient to decompose histamin.
Stated briefly, (1) the results obtained previously by Matsukura and Terakado in their studies on histamin during the course of ileus have been amply confirmed by the use of a quantitative method of McIntire. (2) The present study has explained, in part at least, the machanism by which histamin, formed abundantly in the intestine during ileus, fails to appear in the blood, a point which has been regarded as the most difficult problems by investigators on ileus.
(Author's abstract)


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