[The pancreatico-trophic effect of obstructive jaundice in rats].
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Biomedical subjects
Publications and source records attributed to T Tobe.
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Changes in the ratio of acetoacetate to 3-hydroxybutyrate (the ketone body ratio) in arterial blood were investigated after massive liver resection in patients and rabbits. In a patient who had had a successful hepatectomy, the blood ketone body ratio decreased rapidly after the operation and then returned to the preoperative level; whereas in a patient who had had an unsuccessful hepatectomy, the blood ketone body ratio did not decrease rapidly after the operation. In 70% hepatectomized rabbits, the blood ketone body ratio decreased maximally nine hours after hepatectomy and then returned gradually to a normal level. The blood ketone body ratio paralleled the hepatic energy charge after 70% hepatectomy in rabbits. The measurement of the blood ketone body ratio is very useful for evaluation of the energy status of the remnant liver.
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It is of great importance to define the manner in which cells are damaged and how intracellular derangement becomes irreversible during shock. When supply of both oxygen and substrates to cells is limited during shock, cellular energy metabolism of vital organs is severely depressed. In this experiment, the relationship was clarified between the reversibility of shock and the cellular energy status, from the viewpoint of hepatic energy change, mitochondrial redox state, ATP synthesis of isolated mitochondria, and fragility of mitochondrial membrane in rat livers. The derangement of energy metabolism passed through a series of four stages during hemorrhagic shock. At Stage I (initial stage), the cellular energy level decreased greatly due to marked energy consumption, without any organic damages in the mitochondria. Stage II (cell distress stage) showed that cellular energy imbalance occurred due to the depressed mitochondrial activity in vivo, although it was reversible when the blood supply was restored. Stage III (transitional stage) was the phase at which mitochondrial fragility increased severely. At Stage IV (terminal stage), mitochondria were markedly damaged organically and cellular energy metabolism was not remedied by any intensive therapies, which inevitably meant the death of vital organs.
The effects of hypothermia on adenine nucleotide level, mitochondrial metabolism and redox state of the remnant liver were studied in 25, 50, 70 and 93% hepatectomized rabbits. In 25% of the hepatectomized rabbits, energy charge levels and mitochondrial phosphorylative activities remained unchanged, while in 50 and 70% hepatectomized rabbits, the energy charge levels decreased maximally at 24 hours after hepatectomy with a concomitant rise of mitochondrial phosphorylative activity. In 93% hepatectomized rabbits, the energy charge levels decreased rapidly without enhancement in mitochondrial phosphorylative activity and these rabbits died within 12 hours after hepatectomy. Body cooling significantly increased the energy charge of the remnant liver with further enhancement in mitochondrial phosphorylative activity in 25, 50 and 70% hepatectomized rabbits, but did not increase the energy charge in 93% hepatectomized rabbits. On the other hand, during body rewarming, the energy charge levels of the remnant liver decreased. More than 60% of 70% hepatectomized rabbits died during body rewarming, while all of 50% or less hepatectomized rabbits remained alive. Thus, body cooling may provide remarkable protection for the remnant liver from an energy crisis under the condition that compensatory mitochondrial enhancements are present.
The secretory response of plasma secretin to intrajejunal acid was measured in 11 patients who underwent total pancreatectomy and eight with pancreaticoduodenectomy. In cases of pancreaticoduodenectomy, the secretory response of plasma secretin was well maintained, but in those with total pancreatectomy there was a significantly impaired secretory response of plasma secretin. Among patients with total pancreatectomy, those with Billroth II type anastomosis showed a significantly impaired response compared with those with Billroth I type anastomosis. Thus biliary secretion is more impaired in patients with total pancreatectomy than in those with pancreaticoduodenectomy. To improve the impaired biliary secretion after total pancreatectomy, Billroth I type anastomosis for reconstruction procedure of the alimentary tract appears to be more feasible. In the case of the major pancreatectomy, much attention should be given biliary secretion and such may decrease the possibility of occurrence of ulcer at the anastomosis and improve the digestion-absorption of fat.
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In 25% hepatectomized rabbits, the mitochondrial phosphorylative activity and the energy charge [(ATP + 1/2 ADP)/(ATP + ADP + AMP)] levels of the remnant liver remained unchanged after hepatectomy. In 70% hepatectomized rabbits, the energy charge levels of the remnant liver decreased maximally 24 h after hepatectomy (p less than 0.001), simultaneously with a marked enhancement of mitochondrial phosphorylative activity (P less than 0.001). Afterward, both returned to normal levels within 4 days. In 93% hepatectomized rabbits, the energy charge levels fell rapidly, with an inhibition of mitochondrial phosphorylative activity, within 6 h after hepatectomy. When a 24-hour 70% hepatectomized rabbit was cross-circulated with a normal rabbit, the energy charge in the liver of the normal partner decreased to 0.732 at 30 min after the blood exchange and then returned to 0.855 while that in the remnant liver of the hepatectomized partner increased from 0.767 to 0.820 (p less than 0.001). Also, the energy charge values of a 24-hour 70% hepatectomized rabbit were increased by the extracorporeal normal liver perfusion. It is suggested that a decrease in the energy charge of the remnant liver is due, at least partly, to the accumulation of the substances consuming hepatic energy (hepatodepressant factors) in the systemic blood of hepatectomized rabbits.
Identification of carcinoma arising in the uncinate region of the pancreas is difficult because of the peculiar topographic relationship of this lesion with adjacent structures. Among the various diagnostic procedures performed upon ten patients with this malignant lesion, superior mesenteric arteriography provided the most helpful information, including signs of invasion in the main trunk of the superior mesenteric artery and vein and in the proximal portion of the jejunal arteries. A clearer visualization of these vascular involvements was attained in the right posterior oblique projection rather than in the anteroposterior projection. On the contrary, the arterial and portal vessels belonging to the celiac territory, such as superior pancreaticoduodenal arteries, dorsal pancreatic artery, gastroduodenal artery, splenic vein and portal vein, were almost free of involvement. At laparotomy, almost all of the patients had direct extension of the tumor to the superior mesenteric vessels, forming a cancerous core in the root of mesentery. All died of cachexia within six months after a palliative surgical procedure. Serial roentgenograms of superior mesenteric artery, especially taken in the oblique projection, are the best means of confirming carcinoma of the uncinate process, for which only a few available methods have been established to evaluate the clinical aspects.
The effect of liver support on the adenylate energy charge (ATP + 1/2 ADP) / (ATP + ADP + AMP) of the remnant liver after major hepatic resection was studied in rabbits. The present study emphasizes the principle of the use of homologous or heterologous liver for preventing the decrease in the energy charge of the remnant liver after major hepatic resection. The energy charge level provides the cell with a very sensitive intracellular control mechanism. Regulatory enzymes from biosynthetic sequences exhibit very little activity at low levels of energy charge, and their activities increase sharply at high charge values. The energy charge level of the remnant liver maximally decreased from the normal level of 0.843 to 0.767 at 24 hours after 70% hepatectomy. The energy charge level increased from 0.767 to 0.828 after one hour of cross-circulation of systemic blood between the 24-hour, 70% hepatectomized rabbit and a normal rabbit. An increase from 0.767 to 0.801 also occurred after one hour of charcoal hemoperfusion. Although either means of liver support serves to restore energy charge levels, the above results suggest that cross-circulation may be more effective than charcoal hemoperfusion for biosynthesis in the regenerative processes of the remnant liver.
Changes in the energy substrate utilized by the remnant liver after hepatectomy were studied in relation to the hepatic energy status in 25%, 70%, and 93% hepatectomized rabbits. In 25% hepatectomized rabbits, the energy charge ((ATP + 1/2ADP)/(ATP + ADP + AMP)) level of the remnant liver remained unchanged after hepatectomy and was not affected by portal infusion of (+)-octanoylcarnitine, an inhibitor of fatty acid oxidation. In contrast, the energy charge level of the remnant liver decreased rapidly after 70% hepatectomy and reached the lowest level of 0.77 at 12 to 24 hr after hepatectomy (p less than 0.01). At this time, the energy charge level was further decreased to 0.45 by (+)-octanoylcarnitine (p less than 0.001). It returned to near normal 4 days later. At this time, the effect of (+)-octanoylcarnitine was less evident, with the restoration of the energy change. In 93% hepatectomized rabbits, the energy charge level of the remnant liver decreased rapidly and steeply in the phase immediately after hepatectomy. It is suggested that the remnant liver metabolism switches to predominant utilization of fatty acid as an energy source when the energy charge decreases; it then becomes able to utilize glucose with the restoration of energy charge level. In addition, it is emphasized that hyperosmolar glucose solution or insulin administration during the early period after major hepatectomy should be reconsidered because of their inhibition of the mobilization of free fatty acid from adipose tissue.
Severe alloxan diabetic rats (blood glucose levels, n = 6, 624 +/- 29 mg/dl; peripheral immunoreactive insulin levels (IRI), n = 6, 5.4 +/- 0.9 microU/ml) which had shown impaired mitochondrial phosphorylative activities and low mitochondrial oxidation-reduction states were bled to a mean blood pressure of 40 mm Hg and maintained for 2 hours according to a modified Wiggers' method. Within 2 hours after the induction of shock blood glucose levels rose to still higher levels but no animals died. Roles of hyperglycemia and gluconeogenesis in hemorrhagic shock were discussed, comparing with earlier irreversible results in jaundiced rats that had shown rapid decreases in blood glucose levels and mitochondrial phosphorylative activities in a previous study with rats in hemorrhagic shock.
Studies were conducted to investigate the relationship between development of fibrosis and hemodynamic changes in the pancreas in dogs. The basal blood flow rate in the atrophied, fibrotic pancreas was preserved at almost the same level as in the normal pancreas. Fibrotic pancreas responded to VIP with increased blood flow, but not to administration of secretin. On the other hand, normal pancreas showed a brisk increase of blood flow in response to both of these agents. Our findings suggest that direct arterial acinar blood flow per gram of acini decreases prominently, whereas direct arterial flow to the islets per gram of islet is well maintained after the development of pancreatic fibrosis. It is also suggested that secretin acts indirectly by stimulating metabolic activity of the acinar cells with a secondary increase in blood flow, whereas VIP has a direct effect on the pancreatic vasculature.