Stimulation of oxygen uptake by prostaglandin E2 is oxygen dependent in perfused rat liver

1998 ◽  
Vol 275 (3) ◽  
pp. G542-G549 ◽  
Author(s):  
Wei Qu ◽  
Zhi Zhong ◽  
Gavin E. Arteel ◽  
Ronald G. Thurman
Keyword(s):  
Oxygen Uptake ◽  
Oxygen Tension ◽  
Rat Liver ◽  
Kupffer Cells ◽  
High Flow ◽  
Perfused Rat Liver ◽  
Normal Flow ◽  
Flow Rates ◽  
Glucose Output ◽  
Parenchymal Cells

The aim of this study was to determine if the effect of prostaglandin E2(PGE2) on hepatic oxygen uptake was affected by oxygen tension. Livers from fed female Sprague-Dawley rats were perfused at normal or high flow rates (4 or 8 ml ⋅ g−1 ⋅ min−1) to vary local oxygen tension within the liver lobule. During perfusion at normal flow rates, PGE2 (5 μM) infusion increased oxygen uptake by about 50 μmol ⋅ g−1 ⋅ h−1; however, when livers were perfused at high flow rates, the increase was nearly twice as large. Simultaneously, glucose output was increased rapidly by about 50%, whereas glycolysis was decreased about 60%. When flow rate was held constant, increases in oxygen uptake due to PGE2 were proportional to oxygen delivery. Infusion of PGE2 into livers perfused at normal flow rates increased state 3 rates of oxygen uptake of subsequently isolated mitochondria by about 25%; however, rates were increased 50–75% in mitochondria isolated from livers perfused at high flow rates. Thus it is concluded that PGE2stimulates oxygen uptake via mechanisms regulated by oxygen tension in perfused rat liver. High flow rates also increased basal rates of oxygen uptake: this increase was prevented by inactivation of Kupffer cells with GdCl3. In addition, conditioned medium from Kupffer cells incubated at high oxygen tension (75% oxygen) stimulated oxygen uptake of isolated parenchymal cells by >30% and elevated PGE2production about twofold compared with Kupffer cells exposed to normal air-saturated buffer (21% oxygen). These effects were blocked completely by both indomethacin and nisoldipine. These data support the hypothesis that oxygen stimulates Kupffer cells to release mediators such as PGE2 which elevate oxygen consumption in parenchymal cells, possibly by mechanisms involving cyclooxygenase and calcium channels.

scholarly journals The effect of reduction of perfusion rate on lactate and oxygen uptake, glucose output and energy supply in the isolated perfused liver of starved rats

1979 ◽  
Vol 184 (3) ◽  
pp. 635-642 ◽  
Author(s):  
R A Iles ◽  
P G Baron ◽  
R D Cohen
Keyword(s):  
Oxygen Uptake ◽  
Flow Rate ◽  
Mean Value ◽  
Normal Flow ◽  
Perfusion Rate ◽  
Flow Rates ◽  
Perfusate Flow ◽  
Intrinsic Capacity ◽  
Lactate Uptake ◽  
Glucose Output

1. Lactate and O2 uptake and glucose output were studied in isolated livers from starved rats at perfusate flow rates varying from 100 to 7% of “normal” (11.25-0.75 ml/min per 100 g body wt.). 2. With moderate diminution of flow rate, lactate and oxygen uptake fell more slowly than would be expected if uptake purely depended on substrate supply. 3. Use of a mathematical model suggests that the intrinsic capacity of the liver for lactate uptake is unaffected until the flow rate falls below 25% of “normal”. 4. Some lactate uptake was always observed even at 7% of the “normal” flow rate. 5. At flow rates below 33% of the “normal”, lactate was increasingly metabolized by pathways other than gluconeogenesis, which became a progressively less important consumer of available O2. 6. ATP content decreased with diminution of flow rate, but substantially less markedly than did lactate uptake and glucose output. 7. Intracellular pH fell from a mean value of 7.25 at “normal” flow rate to 7.03 at 7% of the “normal” flow rate.

scholarly journals Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver

1992 ◽  
Vol 281 (2) ◽  
pp. 387-392 ◽  
Author(s):  
Y Hamada ◽  
A Karjalainen ◽  
B A Setchell ◽  
J E Millard ◽  
F L Bygrave
Keyword(s):  
Oxygen Uptake ◽  
Rat Liver ◽  
Bile Flow ◽  
Bile Secretion ◽  
Perfused Rat Liver ◽  
Diseased Liver ◽  
Glucose Output ◽  
Opposing Effects ◽  
Prior Administration ◽  
Slow Onset

Changes in perfusate Ca2+ (measured with a Ca(2+)-selective electrode) and changes in bile calcium (measured by atomic absorption spectroscopy) were continuously and simultaneously monitored after infusion of (a) vasopressin, (b) glucagon and (c) both vasopressin and glucagon together to the perfused rat liver. Also monitored were perfusate glucose and oxygen concentrations and bile flow. Vasopressin induces a sharp, transient, pulse of increased bile flow and increased bile calcium within 1 min of infusion, concomitant with rapid changes in perfusate Ca2+ fluxes, glucose output and oxygen uptake. This is immediately followed by a decrease in both bile flow and bile calcium for as long as the hormone is administered. Changes induced by glucagon are a relatively slow onset of perfusate Ca2+ efflux and oxygen uptake, but rapid glucose output, and a small but significant and transient decrease in bile flow and bile calcium which, despite the continued infusion of the hormone, spontaneously and rapidly returns to normality. However, the greatest responses are observed after co-administration of both hormones. Coincident with the augmented perfusate Ca2+ fluxes (influx) seen in earlier work, there occurs within 1 min of vasopressin infusion a sharp increase in bile secretion and bile calcium greater in magnitude than that produced by vasopressin alone. Immediately thereafter bile secretion and bile calcium decline below basal values and remain there for as long as the hormones are administered. Glucagon and vasopressin therefore each have opposing effects on bile flow and bile calcium. However, the action of vasopressin is enhanced by the prior administration of glucagon. The data thus reveal features about the actions of glucagon and Ca(2+)-mobilizing hormones on bile flow and bile calcium not previously recorded and provide a novel framework around which the whole issue of hepato-biliary Ca2+ homoeostasis can be assessed in normal and diseased liver.

Effects of hematocrit on oxygenation of the isolated perfused rat liver

1983 ◽  
Vol 245 (6) ◽  
pp. G769-G774 ◽  
Author(s):  
G. L. Riedel ◽  
J. L. Scholle ◽  
A. P. Shepherd ◽  
W. F. Ward
Keyword(s):  
Blood Flow ◽  
Oxygen Uptake ◽  
Portal Vein ◽  
Rat Liver ◽  
Male Rats ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Flow Rates ◽  
Perfusate Flow ◽  
Hepatic Portal

The isolated perfused rat liver is used ubiquitously for metabolic and endocrine studies of hepatic function, yet few data are available regarding the inadequacy of the oxygenation of such preparations. Moreover, the isolated rat liver is usually deprived of its arterial supply and perfused via the hepatic portal vein with low-hematocrit or cell-free solutions. To investigate the efficacy of the oxygen supply, we determined the effect of hematocrit on the relation between oxygen consumption and perfusate flow. We then attempted to define a hematocrit at which hepatic oxygenation was maximal. Livers of male rats anesthesized with pentobarbital sodium were perfused via the portal vein with fresh canine red blood cells suspended in Krebs-Ringer-bicarbonate buffer. Perfusions were carried out at various flow rates, and the relation between perfusate flow and oxygen uptake was determined. At flow rates above 100 ml X min-1 X 100 g liver-1, oxygen uptake was independent of flow but below that value was flow limited, regardless of whether the hematocrit was 10, 20, or 40%. To determine the optimal hematocrit for hepatic oxygen uptake, hepatic portal venous and hepatic venous pressures were held at 10 and 0 mmHg, respectively. The hematocrit was lowered in steps from 80 to 10%. Blood flow increased exponentially as hematocrit fell while oxygen uptake increased to a maximum at approximately 20%. It is concluded that an hematocrit of approximately 20% provides the optimal combination of blood flow and oxygen-carrying capacity while maintaining physiological perfusion pressures, e.g., 10 mmHg.

scholarly journals A new method to monitor Kupffer-cell function continuously in the perfused rat liver. Dissociation of glycogenolysis from particle phagocytosis

1990 ◽  
Vol 266 (1) ◽  
pp. 141-147 ◽  
Author(s):  
K B Cowper ◽  
R T Currin ◽  
T L Dawson ◽  
K A Lindert ◽  
J J Lemasters ◽  
...  
Keyword(s):  
Rat Liver ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Cell Function ◽  
New Method ◽  
Carbon Uptake ◽  
Prostaglandin D2 ◽  
Perfused Rat Liver ◽  
Colloidal Carbon ◽  
Parenchymal Cells

In order to study particle phagocytosis and glycogenolysis simultaneously, this study was designed to develop a direct-read-out method to monitor Kupffer-cell function continuously, based on the uptake of colloidal carbon by the isolated perfused rat liver. Livers were perfused for 20 min with Krebs-Henseleit buffer saturated with O2/CO2 (19:1). Colloidal carbon (1-2 mg/ml) was added to the buffer, and absorbance of carbon was monitored continuously at 623 nm in the effluent perfusate. Since colloidal-carbon uptake was proportional to A623, rates of uptake were determined from the influent minus effluent concentration difference, the flow rate and the liver wet weight. Rates of colloidal-carbon uptake were 50-200 mg/h per g and were proportional to the concentration of carbon infused. Data from light-microscopy and cell-separation studies demonstrated that carbon was taken up exclusively by non-parenchymal cells and predominantly by Kupffer cells. Further, the amount of colloidal carbon detected histologically in non-parenchymal cells increased as the concentration of colloidal carbon in the perfusate was elevated. When Kupffer cells were activated or inhibited by treatment with endotoxin or methyl palmitate, carbon uptake was increased or decreased respectively. Taken together, these results indicate that Kupffer-cell function can be monitored continuously in a living organ. This new method was utilized to compare the time course of phagocytosis of carbon by Kupffer cells and carbohydrate output by parenchymal cells. Carbohydrate output increased rapidly by 69 +/- 9 mumol per g within 2-4 min after addition of carbon and returned to basal values within 12-16 min. However, carbon uptake by the liver did not reach maximal rates until about 15 min. Infusion of a cyclo-oxygenase inhibitor, aspirin (10 mM), caused a progressive decrease in carbohydrate output and blocked the stimulation by carbon completely. Aspirin neither altered rates of carbon uptake nor prevented stimulation of carbohydrate release by addition of N2-saturated buffer. The data from these experiments are consistent with the hypothesis that output of mediators by Kupffer cells, presumably prostaglandin D2 and E2, occurs transiently as Kupffer cells begin to phagocytose foreign particles in the intact organ, a process which continues at high rates for hours.

Vanadate inhibits glucose output from isolated perfused rat liver

Hepatology ◽  
1991 ◽  
Vol 14 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Rafael Bruck ◽  
Haia Prigozin ◽  
Zipora Krepel ◽  
Paul Rotenberg ◽  
Yoram Shechter ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Glucose Output

Stimulation of oxygen uptake by glucagon is oxygen dependent in perfused rat liver

1989 ◽  
Vol 256 (2) ◽  
pp. G369-G376
Author(s):  
Z. Kizaki ◽  
R. G. Thurman
Keyword(s):  
Intracellular Calcium ◽  
High Flow ◽  
Perfused Liver ◽  
Normal Flow ◽  
Sprague Dawley ◽  
O2 Uptake ◽  
Intact Cells ◽  
Flow Rates ◽  
Isolated Mitochondria ◽  
Stimulation Of

Livers from well-fed female Sprague-Dawley rats (100-150 g) were perfused at flow rates of 4 or 8 ml.g liver-1.min-1 to deliver O2 to the organ at various rates. During perfusion at normal flow rates (4 ml.g-1.min-1), glucagon (10 nM) increased O2 uptake in perfused liver by approximately 40 mumol.g-1.h-1. In contrast, glucagon increased O2 uptake by nearly 100 mumol.g-1.h-1 when livers were perfused at high flow rates. Increase in O2 uptake was directly proportional to flow rate and was blocked partially by infusion of phorbol myristate acetate (100 nM) before glucagon. Increase in O2 uptake due to elevated flow was not due to enhanced glucagon delivery, since infusion of 120 nM glucagon at normal flow rates only increased O2 uptake by approximately 40 mumol.g-1.h-1. On the other hand, when O2 tension in the perfusate was manipulated at normal flow rates, the stimulation of O2 uptake by glucagon increased proportional to the average O2 tension in the liver. Infusion of 8-bromo-adenosine 3',5'-cyclic monophosphate (BrcAMP; 25 microM) also increased O2 uptake more than twice as much at high compared with normal flow rates. In the presence of angiotensin II (5 nM), a hormone that increases intracellular calcium, glucagon increased O2 uptake by nearly 100 mumol.g-1.h-1 at normal flow rates. Infusion of glucagon or BrcAMP into livers perfused at normal flow rates increased state 3 rates of O2 uptake of subsequently isolated mitochondria significantly by approximately 25%. In contrast, perfusion with glucagon or BrcAMP at high flow rates increased mitochondrial respiration by 50-60%. Glucagon addition acutely to suspensions of mitochondria, however, had no effect on O2 uptake. These data are consistent with reports that glucagon administration in vivo or treatment of intact cells with glucagon increases O2 uptake of subsequently isolated mitochondria, a phenomenon that can account for the observed increase in O2 uptake in livers perfused at high flow rates with glucagon. Furthermore, these results are consistent with the hypothesis that the effect of glucagon on mitochondria is O2 dependent in the perfused liver. This is most likely due to an effect of intracellular calcium on a mechanism mediated via cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Coordinated regulation of hepatic glycogen formation in perfused rat liver by glucose and lactate

1994 ◽  
Vol 266 (4) ◽  
pp. E583-E591 ◽  
Author(s):  
Z. Zhang ◽  
J. Radziuk
Keyword(s):  
Rat Liver ◽  
Dose Response ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Perfused Rat Liver ◽  
Response Curves ◽  
Liver Preparation ◽  
Lactate Uptake ◽  
Glucose Output ◽  
Glycogen Formation

Lactate has been found to enhance the formation of glycogen from both glucose and lactate as substrate (Z. Zhang and J. Radziuk. Biochem. J. 280: 415–419, 1991). To evaluate the relative importance of its role as substrate and regulatory factor, a dual dose-response evaluation was done by adding variable amounts of glucose and lactate to the medium in a recirculating perfused rat liver preparation. Nine groups of perfusions were performed utilizing three different levels of carbon infusion into the system: 0.25, 1.0, and 2.0 mg/min. These levels of carbon infusion were further subdivided into different relative amounts of glucose and lactate. Lactate uptake by the perfused liver was linearly related with net glucose output, regardless of the glucose concentrations. In contrast to this, the effect of lactate uptake on the rate of glycogen synthesis is saturable. Moreover, the rate of glycogen formation at which this saturation occurs is dependent only on the mean perfusate glucose concentration. The highest amount of glycogen formed in a 2-h period was 50 +/- 7 mg and the lowest 3.4 +/- 0.3 mg. A family of dose-response curves was generated describing this dual dependence of glycogen formation (both direct and gluconeogenetic pathways) on lactate and glucose.

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