The author intended to bring into light the problem of the influence of massive transfusion upon patients associated with massive hemorrhage during operations. For this purpose various liver functions in experimental exchange transfusion were determined. The results were as follows.
1) In massive exchange transfusions, liver functions decreased transitorily, since when exchanged volume exceeds three quaters of the recipient's circulating blood volume.
2) The restorement of liver functions in these recipient animals occurs within 24 hours.
3) Single infusions of other fluids than blood cause death of recipient animals due to anoxemia, although there are slight difference atributable to the nature of infusion fluids. Mixing of a equal volume of blood with the above-mentioned fluids can avoid the influence of anoxemia due to infusion.
4) It is desirable that the volume of infusion fluid does not exceed a half of recipient's circulating blood volume, although there may be some exceptions due to the properties of fluids or conditions of patients.
5) Infusion of the mixture of a half volume of blood, a quater of PVP (G) solution and a quater of Moriamin S solution give the best effect on the recipient's liver function.
6) The changes of urobilinogen excretion correlate to those of bromsulphalein excretion, and are transitory.
7) The changes of red cell fragility are slight, and there are no significant difference due to the nature of fluids.
8) With histological examinations, various major organs show hyperemia after blood transfusion, and edema after fluid infusion. The most marked edema is resulted from the infusion of physical saline.

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The author investigated the influence of massive blood transfusion and massive infusion on recipient's kidney, with exchange transfusion experiments in dog and perfusion experiments on extirpated canine kidney. The results were as follows.
1) Renal functions of the recipients increase, when the volume of exchanged blood does not exceed one and a half of the total blood voume of recipient. When the two fold of the recipient's total blood volume is exchanged, transient decrease of the renal functions occurs.
2) When mixtures of the equal volume of blood and various solutions (Ringer's solution, isotonic dextrose solution and amino acid solution) are used, renal disturbance occurs until the cxchanged volume exceeds the total blood volume of recipient.
3) With single infusion of the above mentioned solutions, no significant damage of kidney occurs, until exchanged volume exceeds a half of the total blood volume of recipient.
4) Plasma expanders with higher molecule weight have less deteriorating effects on kidney then those of lower molecule weight.
5) extirpated canine kidney maintains its functions during about six hours with homologous blood perfusion—homologous blood seems to have less preferable effects on extirpated canine kidney than autologous one—, and about three hours with physiological saline perfusion.
6) Renal anoxia less than three hoors causes transient disturbance of renal functions.
7) No remarkable difference is seen among the effects on kidneys perfused with the above mentioned solutions.

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Thermostromuhr and electromagnetic flow meter were used for the study of blood distribution in major organs in massive or oveload blood transfusion in experimental animals with massive bleeding. The results were as follows:-
1) Well balanced exchange transfusions of more than a quarter of recipient's circulating blood volume caused hyperemia in major organs. However, when more than 3/4 or 1 volume of the recipient's circulating blood are exchanged, there has been seen congestion followed by slight ishemia in lung, arteial ishemia following venous ishemia in liver, active congestion in portal system and passive congestion in spleen. Kidney showed hypemia until the exchanged volume reached twice as much as the circulating blood, and thereafter it showed active congestion.
2) On the other hand, head and limbs showed slight ishemia since when the exchanged volume reached a quater of the circulating blood, and this tendency became marked as the exchanged volume increased.
3) In overload transfusion experiments, in which recipients are transfused with double volume of blood drawn off, when the transfused volume exceeded a quater of the circulating blood, blood became to be stored in the major organs especially in the spleen, which acted as a blood depot organ.
4) From these observations, it is concluded that, in practical surgery, overload transfusion of less than 20 per cent of circulating blood volume may scarcely give untoward effect on recipient.

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A nation-wide survey of 2903 clinical cases transfused with more than 1500ml a day in 115 hospitals, was made with regard to the occurrence of side effects, including latent transfusion reactions.
The rate of occurrence of side effects was proportional to the volume transfused with under 3, 000ml daily. This rate was increased in the massive transfusions exceeding 3, 000ml, which should be called “massive” transfusions because of its distinct character.
It has been seen that insufficient blood transfusions augmented the incidence of unfavorable reactions under massive bleeding.
Hemorrhagic tendency and other transfusion reactions seemed to be dependent on intrinsic factors of the recipients rather than extrinsic ones.

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This experiment was attempted to bring to light the production mechanism of auto-antibody, homologous and heterologous antibodies to red cells, as well as the destruction mechanism in vivo of red cells caused by the presence of these antibodies.
Rabbits were used for the experiment.
Consideration was advanced principally concerning the determination of the activity value of Cr⁵¹ labelled on red cells, availing of the specific and convenient nature of isotope Cr⁵¹ and red cells in the ability of association and dissociation with each other, and at the same time a serological experiment on the serum was jointly performed for the consideration.
The survival time in vivo of the same typed as well as different typed red cells was measured after the rabbit's blood was typed with antisera, with the result that the loss curve of both the same type and the different type cells practically coincided with that of the auto-cells.
The repeated infusion of enzyme (trypsin) treated auto-cells into normal and splenectomized rabbits reveals an increased rapidity in the loss of the trypsin treated auto-cells with added frequency of the repetition. On further examining the serum of this particular rabbit, the presence of an antibody to auto-cells was proved.
The experiment made on a splenectomized rabbit by infusion homologous red cells of the same as well as different types, heterologous cells and trypsin treated auto-cells, made it clear that there was no significant difference in the loss curve of homologous cells, but that the losing speed of heterologous cells from the blood flow was extra rapid during the first 30 minutes of its infusion, and also that thereafter the loss curve was obtained almost in parallel with that of a normal rabbit.
With regard to trypsin treated cells it was confirmed that its repeated infusion caused reduction of the loss curve and production of an auto-antibody, regardless of the presence or non-presence of spleen.
The distribution of the infused normal auto-cells, trypsin treated auto-cells and heterologous cells was examined in heart blood, liver, spleen and kidney to find that the distribution of heterologous cells in the sysem was considerably different from that of homologous cells.
Of the blood cells denatured by trypsin treatment, the homologous cells and the heterologous cells differ remarkably in the way they are destroyed and disposed, but the homologous cells which have been subjected to a powerful irreversible change are disposed in the liver in compensation of the spleen, same as heterolgoous cells.

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One of the practical disadvantages of preserved blood, compared with fresh blood, is the slowing down of transfusion drip rate. It is previously pointed out that this phenomenon is due to the venospasm, which occurs at the area proxismal to the site at which needle is inserted.
The author investigated the mechanism of this phenomenon, and obtained the results as follows.
1) The plasma of preserved blood causes contraction of the isolated strip of colon of the rat as well as the isolated spirally opened strip of the human vein.
2) Evidence is presented that this effect is not due to potassium, histamine, adrenaline, nor-adrenaline, acetylcholine or serotonin.
3) The active substance in the plasma was found to be released from a-globulin fraction of plasma in the presence of destroyed platelets.
4) The yellowish active substance was obtained from the preserved plasma.
5) Preservation of whole blood in siliconized bottle to minimize the destruction of platelet is proved to be effective in preventing the production of the active substance.

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Studies were carried out with regard to the changes of coagulating mechanism in patient with hemorrhagic tendency induced by massive transfusion of stored blood, as well as in dogs with experimental hemorrhagic shock, hypoxia and after massive exchange transfusion (100cc/kg). A correlation between reduction of circulating platelets and prolongation of bleeding time was found in surgical patients and dogs given a massive blood transfusion.
Incomplete production of thomboplastin was proved to be an important changes in coagulating mechanisms after that occurred after a massive blood trausfusion this was mainly due to the impediment of the third factor of platelet.
Accordingly, the changes in circulating platelets seemed to be the main contributing factor to the manifestation of hemorrhagic tendency after massive transfusion, both with respect to vascular and clottng factors.
Since the appearance of fibrinolysis is closely associated with hemorrhagic shock and operative invasion etc, it does not seem to be a primary factor but a factor promotng a hemorrhagic tendency. Hypoxia intensified hemorrhagic tendency due to the disturbance of the second phase of coagulation.
Pre-operative impairmut of liver function and hepatic damage resulting from massive blood transfusion seemed to promote the second phase of coagulation.

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