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Effects of atropine, physostigmine, duvadilan and tetrodotoxin on the mechanical activity of the longitudinal muscle preparation of dog's stomach in vitro experiments and on the motility of stomach in the same animal in vivo experiments were investigated. 1. The latency of an atropine-resistant contraction which was produced by stimulation of vagus nerve was increased in period in accordance with the augmentation of concentration of atropine in vitro experiments. 2. Physostigmine reconstructed the atropine-resistant contraction which was abolished by duvadilan as well as the cholinergic contraction which was abolished by atropine in vivo experiments. 3. Duvadilan abolished the cholinergic and atropine-resistant contractions in vitro, but in vivo experiments duvadilan abolished only the atropine-resistant contraction. 4. An atropine-resistant contraction was completely abolished by administration of tetrodotoxin. But the direct electrical stimulation of the muscle caused the contraction of it which was blocked by tetrodotoxin.

Arterial and venous blood flow and oxygen saturation of the venous blood in the mesenteric vessels arising from single mesenteric artery and vein to the intestinal loop in anesthetized dogs were measured simultaneously with systemic arterial blood pressure during distension of this loop. Mesenteric arterial blood flow decreased to the zero level, while mesenteric venous outflow increased to about twice the quiescent level at the onset of elevation of intraluminal pressure. However, during distension, the decreased arterial blood flow tended to increase, but the increased venous flow was reduced to one half of the quiescent level. Oxygen saturation of venous blood diminished initially and then increased progressively during distension. At the end of distension venous outflow stopped temporarily. After suspension of distension, arterial and venous flow and oxygen saturation increased beyond the quiescent level. These results may suggest that there is a by-pass or A-V anastomosis which cannot be compressed mechanically by elevation of intraluminal pressure.

1. A study was made in vivo experiments of a contraction of stomach of the dog to stimulation of the extrinsic nerves, medulla oblongata and thoracic cord in the presence of atropine. 2. An atropine-resistant contraction of stomach was produced without accompanying any preceding relaxation of stomach motility. It seems to deny that an atropine-resistant contraction appears to be a rebound phenomenon. 3. An atropine-resistant contraction was produced in prolonged stimulation. A delay of latency to produce a contraction of stomach was more than 27 sec and a contraction was decreased in amplitude and frequency in the presence of atropine.

1) We have made clear the periodic contractions in the volume of such organs, as the spleen, intestine, kidney, etc., and the periodic changes in the venous and arterial blood pressures, resulting from above phenomena (8, 9, 10). However, now we were able to observe the volume changes of periods ranging from 15 to 38seconds in the liver, brought about by intravenous injections of Ringer's solution, sodium citrate, etc. (fig. 1 and 2).2) The connection between the change in liver volume and respiration is, during expiration, the liver volume decreases, while during inspiration it increases, but as can be seen in fig. 2, during rhythm occurrence in the liver, no changes could be seen in this amplitude of the respiration on the curve of liver volume. Also no changes in amplitude were observed on the respiratory curve, transmitted from the thoracic wall (fig. 1). Furthermore, directly after an intravenous injection of a solution of sodium citrate, a change occurred in the respiratory movement but this was different from the periodic change in the liver volume.3) Bainbridge and Dale (2) have shown that periodic contractions occur in a gall-bladder, and the periods were approximately 3 times per minute. This is quite similar to what we have seen in the liver, but periodic contractions can also be seen in a liver from which the gall-bladder has been completely removed (fig. 1), so it is quite correct to assume that in our cases this was not caused by the contraction of the gall-bladder.4) The fact that the splanchnic nerves control the liver is beyond doubt (6), but by their severance or even by the severance of the vagus nerves of both sides, the occurrence of a periodic volume change in the liver could not be disappeared. This phenomenon was also seen after the hepatic artery had been ligated. Thus, from the above facts we can see that the periodic changes seen on the volume curve of the liver have connections with the liver tissue proper and with the hepatic vessels.5) However, two types of periodic volume change in the liver can be differentiated. The first, as shown in fig. 1 and 2, is when the direction of change in the liver and the changes in the arterial and venous blood pressure are the opposite, namely when the contraction of the liver caused a rise in portal and arterial pressure. The other as shown in fig. 3 is when the 3 changes are in the same direction, namely the rise in portal and arterial pressure are observed simultaneously to the increase in the liver volume.6) In the cases shown in fig. 1 and 2, since the change in portal pressure and the change in liver volume showed opposite directions, the change in liver volume is thought an active one and based on contractions of the liver. This causes an increase in resistance of the portal blood flow, thus it can be considered as producing an increase in portal pressure. Regarding the active contraction of the liver, it contracts in response to stimulation of the splanchnic nerves (6), and also contracts markedly to adrenaline (7). Also regarding the existence of smooth muscle in the liver, there are reports that it has been found not only in the hepatic veins but also in the cental and sublobular veins (1).On comparing the periods of contraction confirmed in the spleen, intestine and kidney, with that of the liver, they are both approximately 25seconds, and stimulations which cause periodic contractions in the spleen etc., also cause rhythmical volume changes in the liver. This gives us grounds to suppose that the periodic contractions of these organs are but the rhythms of their smooth muscles.7) The case cited in example 1 of table 1, shows that the volume change of the liver was 0.65 to 1.0cc. and that the change in portal venous pressure was 6-16mm. saline. This change of pressure corresponds to 11.9% of its portal pressure.

1) By stimulating the central end of the depressor nerve of a dog with a tetanic inductive current a decrease in volume of the liver, simultaneous to fall in the general arterial blood pressure and the portal pressure were observed (see exp. 1). This decrease, as shown in fig. 1 is 0.9-2.4cc. and this result is the directly opposite to the reports of Harada (6) and Richter (9), who obtained a 3.1% increase in volume, in experiments with rabbits.2) However, in order to know whether this decrease in the volume of the liver, occurs in the hepatic artery area or in the portal area, the blood flow of the hepatic artery was temporarily occluded, and also the portal blood flow into the liver was constricted as shown in exps. 2 and 3, decrease in the volume of the liver was confirmed in both cases. Namely, due to the depressor reflex, both blood vessels areas show that they are connected with the decrease in the volume of the liver.Harada (6) reports that normally, due to depressor stimulation, there is an increase in volume of the liver, but a decrease, after ligature of the hepatic artery. However, in our experiments, regardless of the existence or non-existence of a blood flow in the hepatic artery, an one-sided change, namely, a decrease in the volume of the liver occured (see exp. 2)3) On the other hand, it may be considered that the liver blood vessels may dilate by the depressor reflex, however the decrease in the general blood pressure and the portal venous pressure caused by the stimulation of the depressor nerve are so much that the dilatation of the hepatic blood vessels can not be observed on the volume change in the liver. However, this observation can be discarded by the perfusion experiment (see exp. 5) or the experiment whereby the blood flow into the liver of both the hepatic artery and the portal vein were shut off (see exp. 4). Namely, in exp. 4, when the hepatic artery and the portal blood flow into the liver were stopped temporarily, no changes occurred in the volume of the liver, due to the depressor reflex (when adrenaline is injected into the liver tissues proper, even after the stoppage of both blood flows, the volume of the liver shows a decrease).Furthermore, as shown in exp. 5, when the perfusion experiment of only the liver in situ, is carried out, even though there may be a fall in the general blood pressure, no change could be confirmed in the volume of the liver.4) Hence the above experiments would indicate that the change in the volume of the liver due to the depressor reflex is a passive one, caused by the fall of the hepatic arterial pressure and the portal venous pressure, and not an active contraction of the hepatic blood vessels.

The effects of tonic and rhythmic contraction of the intestine on the arterial and venous blood flow through the intestinal segment were investigated in dogs.Intestinal contractions always caused periodicity in the arterial and venous blood flow. The correlation between intestinal contraction and the arterial and venous flow was classified into three patterns; the contraction phase type, relaxation phase type and combination type were observed in tonic contraction, and the contraction phase type and relaxation phase type in rhythmic contraction.In the contraction phase type, augmentation of venous flow and diminution of arterial flow was elicited during the contraction period. In the relaxation phase type, diminution of venous and arterial flow during the contraction period was followed by sustained augmentation of flow during the relaxation period. The combination of these two patterns is the combination type.Augmentation of venous outflow during the contraction period was produced by expelling blood from the intestinal wall, as the arterial inflow was diminished during this period. Augmentation of arterial and venous flow during the relaxation period was caused by vasodilatation due to prolonged compression of the blood vessel by contraction of the intestinal musculature.

The influence of electrical stimulation of the medulla oblongata and associated structure on gastric motility of anesthetized and non-anesthetized dogs was studied.Increase in gastric motility was observed on stimulation of the dorsal nucleus of the vagus, the solitary tract and its nucleus and the dorsal region of the reticular formation.Inhibition of gastric motility was obtained on stimulation of the solitary tract and its nucleus, the dorsal region of the reticular formation and the dorsal nucleus of the vagus.The efferent pathways for excitatory effects from the medulla oblongata were not only the vagus nerves but also the splanchnic nerves. The efferent pathways for inhibitory effect were also the splanchnic nerves and the vagus. Diagram presented in FIG.7 illustrates the regulation center upon the excitatory and inhibitory centers for stomach motility and the efferent pathways from them to the stomach.

1) A rapid increase in bladder pressure regularly caused an increase in contraction of the stomach and inhibition of the small intestine. Tne motor response was usually produced in the dog which has a strong peristaltic contraction of the stomach. The inhibitory response of the small intestine was reversed to a motor response by applying nicotine to the coeliac plexus.2) The motor afferent nervous pathway is the pelvic nerves, and this can also be demonstrated by the central stimulation of the pelvic nerves. Tne inhibitory afferent nervous pathway is the hypogastric nerves which can also be demonstrated by the central stimulation of the hypogastric nerves.3) The efferent nervous pathways of the motor and inhibitory response of this reflex are contained in both the splanchnic and vagus nerves.

In experiments on dogs the influences of peristaltic contraction of the distal colon on blood flow through the colonic vein were studied. Blood flow was recorded continuously by electro-magnetic flow-meter.The peristaltic contraction of the distal colon caused the periodicity on the flow-meter tracing of the colonic vein.Three groups of the correlation between the peristaltic contraction and venous blood flow were observed. The first pattern is that the abrupt augmentation of the colonic blood flow was elicited during the contraction. The second pattern is that the diminution of colonic blood flow during the contractile phase was followed by the sustaining augmentation of the blood flow during the relaxation. The above mentioned two patterns being in combination is the third pattern. That is, the augmentation of the blood flow during the contraction was followed by the diminution of blood flow corresponding to the highest level of contraction and by the sustaining augmentation of blood flow during the relaxation. The third type was usually elicited by the stimulation of the pelvic nerve.The initial augmentation of blood flow is due to propulsive action on the blood within the colonic vessels. The secondary augmentation of blood flow is depended on the vascular dilatation which is caused by the obstruction of blood flow through the colon during the prolonged contraction.

The atropine-resistant contraction of the alimentary canal, first reported by CAMPBELL (1966) and subsequently confirmed by others, was examined in dog in vivo. The gastric and colonic motor excitations were examined by stimulating the extrinsic nerves, the medulla oblongata or the spinal cord and its roots. Prolonged stimulation of the vagus, medulla oblongata or splanchnic nerve, thoracic cord and its dorsal root produced excitation of the gastric motility even after intravenous injection of sufficient atropine, although the intensity and frequency of peristalsis were slightly reduced. Prolonged latent periods were characteristic of the atropine-resistant excitation in the stomach, the latency being 29.8--49.4 sec as compared to 2.3--14.5 sec in control (without atropine). On the other hand, the colonic excitation induced by the stimulation of the pelvic nerve, or sacral cord and its ventral root was not inhibited by atropine; no prolongation in latency and reduction of peristalsis was observed.

The effects of tonic and rhythmic contraction of the gut on venous blood flow and oxygen saturation in venous blood through an intestinal segment were investigated in anesthetized dogs.Intestinal contraction caused periodicity not only in venous outflow but also in oxygen saturation in venous blood.(1) It was observed in tonic contraction that augmentation of venous outflow synchronized with reduction of oxygen saturation in venous blood and that diminution of venous outflow produced an increase of oxygen saturation in venous blood.(2) In rhythmic contraction, the correlation between venous outflow and oxygen saturation in venous blood could be classified into two patterns. In the first pattern fluctuations of venous outflow corresponded reciprocally to fluctuations of oxygen saturation, and in the second pattern both curves fluctuated parallel to each other.The mechanism of the correlation between venous outflow and oxygen saturation in venous blood in each type is discussed.

The effect of rhythmical contraction of the spleen on the splenic venous flow was studied. The rate of blood flow through the splenic vein was determined in dogs which maintained an almost constant systemic blood pressure before and after the rhythmical contractions was induced. Normal splenic blood flow averaged 2.77ml per minute, but increased to 3.22ml per minute on the average during the period of rhythmical contractions. This increase corresponded to 16.2% of the normal splenic blood flow. This suggests that the rhythmical fluctuation in splenic blood flow accelerates the blood flow in the portal vein.

The increased motor response of the gastro-intestinal activity caused by peripheral stimulation of the splanchnic nerve, thoracic sympathetic trunk and its dorsal roots was studied on anesthetized and unanesthetized dogs and toads.1) Peripheral stimulation of the splanchnic nerve and thoracic sympathetic trunk, causes universally inhibition of gastro-intestinal motility and at times, produced augmentation. The conditions capable of producing the motor response in the normal animals are different in the individuals.2) After blocking the coeliac and superior mesenteric ganglia, stimulation of the splanchnic nerve and theracic sympathetic trunk always produce augmentation of the movement. The blockade of these ganglia was the indispensable condition necessary in producing the increased gastro-intestinal motor response by sympathetic stimulation.3) By peripheral stimulation of the dorsal root of the thoracic cord, motor augmentation of gastro-intestinal motility can always be obtained. The motor response is not influenced by the block of the coeliac and superior mesenteric ganglia and the ganglia of the thoracic sympathetic trunk.After a nicotine-solution is injected into the spinal ganglia, stimulation of the dorsal roots has no effect on gastro-intestinal activity.Stimulation of the ventral root of the thoracic, cord always. causes inhibition.After blocking the coeliac and superior mesenteric ganglia, this inhibitory effect almost totally disappears.

The enteric stimulation by hypertonic saline solution or tetanic current ofone loop of the small intestine elicits the inhibitory reflex responses in anotherloop through the decentralized coeliac and superior mesenteric ganglia.

The influence of stimulation of the lumbar ventral root and the dorsal root on the distal colon has been investigated. The chief results thus obtained may be summarised as follows:1) In anesthetized and unanesthetized dogs, peripheral stimulation of the ventral root (L2-L7) constantly caused an ihibitory effect of the distal colon, and the dorsal root stimulation (L2-L7) caused always a motor effect. However, the reverse effect did not occurred under any condition.2) The effect of ventral stimulation was abolished after blocking the inferior mesenteric ganglion by application of nicotine or a C6-solution. However, the effect of dorsal root stimulation was not influenced by the block of the ganglion. This shows that the inhibitory fibers have nerve-cells in the inferior mesenteric ganglion, however, the motor nerve do not have any nerve-cell connections in it.3) The motor effect is augmented by eserine solution and abolished by atropine.