[Gallbladder motility after gastrectomy].
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Biomedical subjects
Publications and source records attributed to Y Ohira.
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1. Responses of enzymic characteristics of gastrocnemius muscle were studied when frogs (Rana pipiens) were exposed to cold environment (4 degrees C). 2. The content of adenosine triphosphate (ATP) decreased significantly after cold exposure. This decrease was greater in starved than in fed frogs. 3. Although the glycogen content did not change, lactate levels were lower in cold-exposed than room-temperature (control) frogs. No change was observed in glycogen and lactate between fed and unfed frogs kept at 4 degrees C for 2 months. Lactate dehydrogenase activity tended to increase during chronic cold exposure, but not significantly. 4. The activities of citrate synthase, cytochrome oxidase, and beta-hydroxyacyl CoA dehydrogenase were higher in gastrocnemius of chronically cold-exposed frogs than in room-temperature controls. This increase was statistically significant only in the muscles of starved frogs; these muscles had the greatest decrease in ATP. 5. It was suggested that chronic cold exposure decreases skeletal muscle ATP content but may not affect glycolysis. The data also suggested that the decrease in ATP content stimulates mitochondrial biogenesis which increases enzyme activities.
The motor activity of the canine lower esophageal sphincter (LES) was studied under conscious states by means of the strain gage transducer, and gastroesophageal reflux was investigated after injection of the contrast medium through the silastic tube inserted in gastric fundus by x-ray. The motor activity and function of LES were observed in the dogs with selective proximal vagotomy (SPV), truncal vagotomy (TV) and TV + gastrectomy. Results were summarized as follows; 1. In the postprandial period, so called receptive relaxation was observed in gastric body, and tonic contraction was observed in LES. On the other hand, the occurrence of the LES contraction was consistent with gastric periodic motor activity in the interdigestive state. It was found that such a contractile pattern of LES and gastric body prevented the reflux of gastric juice from stomach to esophagus in the digestive and interdigestive state. 2. In the postprandial period, the tonic contraction of LES was inhibited by the venous injection of atropine sulfate. Mechanisms of digestive contractile activity of LES were mainly regulated by cholinergic nerve. 3. After SPV and TV, the motility of LES and gastric body was disturbed. Namely, receptive relaxation disappeared, and tonic contraction was observed in gastric body, but the relaxation of the LES was found after ingestion. These findings suggested that discordant LES contractiles with the contraction of the gastric body after vagotomy produced a gastroesophageal reflux. 4. After TV + gastrectomy, the synchronous motor activity of the LES, remnant stomach and duodenum disappeared. Namely, it was thought that the reflux esophagitis occurred after gastric surgery with vagotomy and lymphnodes dissection was caused by the duodenal juice reflux to remnant stomach and esophagus.
Using adult mongrel dogs, remnant gastric motility in relation to the changes of gastrointestinal hormone (gastrin and motilin) levels were measured under conscious states before and after distal partial gastrectomy in the Billroth I (BI) or II (BII) reconstruction and proximal partial gastrectomy with or without pyloroplasty. Remnant gastric motility was studied during the digestive and interdigestive states by chronically implanted strain gage transducer (S.G.T.) along the gastrointestinal tract. Gastrointestinal hormone levels were determined by radioimmunoassay. Results were summarized as follows: 1. Remnant gastric motility after BI was different from BII, that is, digestive patterns after BII were more shorter than BI, as a result, gastric emptying times were shortened. 2. Gastrin release by the meal intake in the dogs with BI was greater than that in BII. On the other hand, motilin release in the dogs with BII was higher level than that in BI during the digestive and interdigestive states. Gastrointestinal hormone levels after BI were approximately as same responses as controls. These findings suggested that BI reconstruction for distal partial gastrectomy was more physiological surgical procedure than BII reconstruction. 3. Remnant gastric motility during the digestive state after proximal gastrectomy showed the excitatory pattern and gastric emptying time was remarkably shortened than in controls. 4. In gastrin and motilin levels stimulated by the meal in the dogs with proximal gastrectomy, the peak of gastrin and the depression of motilin were observed more early in relation to remnant gastric emptying time. These findings suggested that the pyloroplasty for the proximal gastrectomy was necessary to prevent an increased motility of the remnant stomach during the digestive states.
Effect of creatine depletion by beta-guanidinopropionic acid (beta-GPA) feeding on mitochondrial morphology was studied in rats. Following beta-GPA feeding for 9 weeks, intramitochondrial inclusions running parallel to the long axis of mitochondrion were observed in skeletal muscles. A bundle of inclusions consisted of four parallel arrays containing electron-dense materials. Two outer arrays were continuous with cristal membranes and two inner arrays were chains of fine particles. Mitochondria with such inclusions were elongated probably in only a certain direction even though it was suggested that the layers of cristae were straightened two-dimensionally. Longer mitochondria ran parallel to the muscle fibers. It was also suggested that chronic stimulation of mitochondrial biogenesis by depletion of high energy phosphates may induce such inclusions within mitochondria.
Young rats maintained on an iron-deficient diet developed severe anemia and had large decreases in the levels of the iron-containing flavoproteins and cytochromes of the mitochondrial respiratory chain in skeletal muscle. In contrast, the levels of a number of mitochondrial matrix marker enzymes, including citrate synthase, isocitrate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and aspartate aminotransferase, increased in red skeletal muscle but not in white muscle. Phosphocreatine concentration was decreased and inorganic phosphate concentration was increased in soleus muscle frozen in situ. We hypothesize that the increase in mitochondrial matrix enzymes reflects a stimulus to mitochondrial biogenesis in posture-maintaining and weight-bearing red muscle fibers in severely iron-deficient rats. It is our working hypothesis that this stimulus to mitochondrial biogenesis arises from mild activity of the red fibers and is due to the same perturbation in cellular homeostasis that is normally caused by vigorous exercise or hypoxia. In iron deficiency, the stimulus to mitochondrial biogenesis can induce an increase in only those enzymes not prevented from increasing by iron deficiency, resulting in formation of mitochondria of grossly abnormal composition.
It has been reported that the mitochondrial cytochromes and citrate cycle enzymes occur in constant proportions to each other and increase or decrease roughly in parallel in response to various stimuli. The purpose of this study was to determine whether this proportionality is an obligatory consequence of the way in which mitochondria are assembled. Severe iron deficiency was used to bring about decreases of the iron-containing constituents of the mitochondrial respiratory chain in skeletal muscle. Cytochrome c concentration and cytochrome oxidase activity were decreased approximately 50%, while succinate dehydrogenase and NADH dehydrogenase activities were decreased by 78% in iron-deficient muscle. On electron microscopic examination, mitochondria in iron-deficient muscles had relatively sparse numbers of cristae. The iron deficiency had little or no effect on the levels of a range of mitochondrial matrix enzymes, including citrate synthase, isocitrate dehydrogenase, fumarase, aspartate aminotransferase, 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacid-CoA transferase, and acetoacetyl-CoA thiolase. These results show that the usual constant proportions between the constituents of the mitochondrial respiratory chain and matrix enzymes are not obligatory; they provide evidence that mitochondrial matrix enzymes and respiratory chain constituents can be incorporated into mitochondria independently and that the ratios between them can vary within wide limits.
UNLABELLED: Serum gastrin changes before and after selective proximal vagotomy (SPV) were studied in relation to the gastric motility and the acid secretion clinically and experimentally and the effects of pyloroplasty were investigated. RESULTS AND CONCLUSIONS: Experimental studies revealed that test meals provoked gastrin secretion to stimulate gastric motility. Periodical gastric acid secretions were observed during hunger period, along with elevated serum gastrin levels. After SPV, gastrin responses to the test meals were significantly increased so that the pyloric ring motility was disturbed. Clinical studies revealed that adrenaline infusion test provoked significant gastrin responses to secrete acid secretions in duodenal ulcer patients. After SPV, increased gastrin responses to adrenaline restored acid secretions as much as preoperative acid secretions responded to the adrenaline test. Pyloroplasty for the SPV inhibited the gastrin and acid secretions responded to the adrenaline test.
Effects of dietary iron deficiency on growth, the distribution of hemoglobin (Hb) at rest and during exercise, the characteristics of muscle fiber types, and glycogen depletion patterns were studied in newly weaned male mice. Forty-eight mice were randomly divided into iron-deficient and control diet groups. Severe iron deficiency impaired general growth, but growth was restored following iron repletion. The mean +/- SEM blood Hb concentrations at rest after 7 weeks were 5.8 +/- 0.7 and 12.5 +/- 0.3 g/dl in iron-deficient and control groups, respectively. The mice fed iron-deficient diet for 7 weeks had an increased Hb level of 10.9 +/- 0.5 g/dl 1 week after an i.p. injection of Imferon (1.25 mg Fe). The Hb contents in brain and gastrocnemius as well as whole body were lowered by iron deficiency. Iron-deficient anemic mice tended to increase the percent distribution of Hb to brain during exercise. This value was significantly greater than in control and iron-treated groups. The iron-deficient group had relatively less glycogen than controls, but no significant tendency in glycogen depletion pattern was observed in any fiber types. It is suggested that decreased Hb content in working muscles due, in part, to greater distribution to brain could be one of the limiting factors for work performance in anemic individuals. It is further suggested that decrease in oxidative muscle fibers as well as the decreased concentration and/or activities of oxidative substances may also be one of the limiting factors.
The effects of iron deficiency anemia and iron treatment on blood gas and acid-base balance at rest and during exercise were studied. Eight Sri Lankan males and 13 females were randomly divided into an iron treatment or placebo group. Their initial hemoglobin (Hb) levels were 6.2 +/- 0.5 and 5.5 +/- 0.7 g/100 ml (mean +/- SEM) with serum iron levels of 41 +/- 8 and 30 +/- 6 micrograms/100 ml, respectively. Hemoglobin concentration was increased significantly within 7 days after iron treatment to 7.2 +/- 0.4 g/100 ml. Resting lactate was higher than normal, while base excess, buffer base, and actual bicarbonate were lower, maintaining a normal pH. Heart rates during exercise at a given work load and lactate production following exercise decreased after the elevation of Hb. Venous blood PCO2 rose as Hb concentration increased, preceding a significant increase in resting O2 content, 16 days after iron treatment. With anemia, O2 delivery is potentially maintained by a shift of the O2-dissociation curve to the right due, in part, to 2,3-diphosphoglycerate. There was no significant change in PO2 or Hb-O2% saturation following exercise or iron treatment. These data suggest that severe iron deficiency anemia results in lactate accumulation in blood even at rest but pH is maintained within normal limits. It was also suggested that severe anemia may impair CO2 transport capacity of blood which could limit continuation of muscle metabolism.
Effects of dietary iron deficiency on lactate metabolism were studied in weanling female rats. Following an iron-deficient diet for 5 weeks, mean hemoglobin concentration was lowered to 6.4 g/dl relative to 12.2 in the control group. Mean plasma iron levels were 58 and 162 micrograms/dl, respectively. Significantly elevated resting lactate levels were observed in whole blood and plasma from iron-deficient anemic (relative to control) rats. Total activity of lactate dehydrogenase (LDH) was elevated in soleus and gastrocnemius muscles in response to iron deficiency from 269 +/- 51 to 364 +/- 60 (Mean +/- SD) and from 265 +/- 65 to 372 +/- 61 IU . 10(-3) . g-1, respectively. The LDH activity in heart was lowered from 700 +/- 61 to 593 +/- 45 IU . 10(-3) . g-1. The M3H and M2H2 isozymes in soleus were increased from 12.7 +/- 2.8 to 20.4 +/- 5.8% and from 19.4 +/- 6.1 to 28.2 +/- 3.6%, respectively. Similar increase was observed in M2H2 and MH3 in gastrocnemius from 9.8 +/- 0.9 to 14.8 +/- 2.0% and from 17.4 +/- 2.0 to 20.5 +/- 2.3%, respectively. The H4 isozyme was significantly reduced in soleus, gastrocnemius, and plantaris muscles from 27.7 +/- 4.7 to 12.4 +/- 4.4, from 15.8 +/- 1.9 to 7.2 +/- 2.9, and from 10.5 +/- 2.9 to 3.9 +/- 2.1%, respectively. It was suggested that iron-deficiency anemia induces an elevation of lactate production following an increase in total LDH activity and change in LDH isozyme patterns.
The time course of metabolic and physiological adjustment to moderate iron deficiency anemia (MIDA, 8 g Hb/dl) and to severe iron deficiency anemia (SIDA, 4 g Hb/dl) was studied in adult, male Sprague-Dawley rats at 3, 7, 14, 30, 60, 90, 150, and 360 days, respectively. Our previous studies using the same rats used in the present study indicated that bone marrow iron was absent and plasma iron was significantly lower (p less than 0.001) in MIDA and SIDA relative to control. The following results with MIDA and SIDA rats are all expressed relative to control values. Red cell 2,3-diphosphoglycerate ranged from 45 to 146% greater in MIDA over the 360-day period and was 130% greater in SIDA at 30 days. Exhaustive run time consistently averaged 64 +/- 3% (SEM) less in MIDA over the time course and was further lowered to 18% in SIDA at 30 days. Heart rates of MIDA were elevated (p less than 0.05) at 180 days but lower (p less than 0.001) at 360 days in response to exercise. Resting heart rates of MIDA were the same at 180 and 360 days. Heart rates of SIDA were elevated (p less than 0.05) at rest and during exercise at 30 days. Organ weight/body weight changes indicated cardiomegaly in MIDA from 90 to 150 days which reverted to normal at 360 days; splenomegaly in MIDA from 90 to 360 days; and kidney atrophy in MIDA at 60 and 90 days which reverted to normal thereafter; in SIDA cardiomegaly and splenomegaly were present at 30 days. These results indicate that the onset and magnitude of physiological and metabolic adjustments occur in proportion to the severity of the anemia, and despite compensatory adjustments in parameters related to work performance, a new stable, lowered level of work tolerance is reached.
Iron may affect both respiratory O2 transport and mitochondrial electron transport in the performance of muscle work. This study was designed to elucidate the molecular defect of iron-deficient work performance by identifying heretofore unmeasurable mitochondrial enzymes that are diminished by iron deficiency and may be restored by iron repletion. Female rats were made iron-deficient by dietary control and were repleted by oral iron. Iron deficiency reduced physical work capacity (treadmill running time), haemoglobin (Hb), and mitochondrial iron-sulphur (Fe-S) centres in heart and skeletal muscles; mitochondrial number was unaffected. Oral iron supplementation restored work capacity and Hb within 4 d to normal or near-normal levels, but in general Fe-S centres of mitochondria due to NADH dehydrogenase remained at iron-deficient levels. Subnormal concentrations of mitochondrial iron-dependent NADH dehydrogenase in muscle are not by themselves rate-limiting in work performance.
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Effects of thermal dehydration without exercise on leukocyte differentials, serum protein fractions, and other hematologic characteristics were studied in six healthy subjects. Both leukocyte and serum total protein levels increased beyond that predicted by hemoconcentration alone. Eosinophil counts decreased significantly, although other leukocyte counts tended to increase. Serum globulin concentrations tended to increase, but the albumin level did not change. Serum K+ concentration was elevated, but Na+ and Cl- were unaffected. It is suggested that thermal dehydration affects blood leukocyte composition and protein metabolism in many of the same ways as physical exercise.
Selected parameters related to work tolerance were measured in 31 adult subjects with hemoglobin (Hb) concentration from 2.5 to 14.0 g/100 ml. Work tolerance was closely related to Hb concentration (r = 0.74) regardless of the adequacy of storage iron level. One male and six females with a mean Hb of 3.5 g/ml (27-55 years old) were studied before and 24h after transfusing 570ml of whole blood. The mean maximal work load tolerated increased 83% within 24h after transfusion in these seven subjects. Post-exercise venous blood lactate was markedly lower after transfusion. Work tolerance of these subjects within 24h after transfusion was the same as in other subjects who had had the equivalent Hb level as the post-transfusion subjects presumably for at least several weeks. These data suggest that the decrement in work performance capacity in iron-deficient and anemic subjects is, in a large part, a reflection of the level of anemia rather than other non-Hb related biochemical changes that could accompany prolonged iron deficiency anemia.
The relative importance of hemoglobin (Hb) and non-Hb iron for physical work capacity was studied in 45 adult male and female subjects, with a range of Hb and serum iron levels. Maximal work capacity, heart rate, venous blood lactate and serum protein were measured before and after 1 week of treatment with Imferon, i.v. Even though some non-Hb related effects on parameters indicative of maximal work capacity were found, the main factor was Hb related. Subjects with low Hb-high serum iron worked longer than ones with low Hb-low iron. When work performed was similar, the marginal Hb-low iron group had a higher blood lactate concentration than the high Hb-high iron and marginal Hb-high iron groups. The coefficient of correlation between serum iron and post-exercise lactate levels was -0.41 (p less than 0.05). Even though neither of these groups showed a Hb response within 1 week of iron treatment, the initial low serum iron groups had significantly lower heart rates at a given work load relative to subjects with high iron but with a similar Hb level. This occurred both at rest and during light to heavy exercise. These results suggest that a rather rapid benefit of iron treatment is gained in iron-deficient subjects with severe and moderate anemia which cannot be accounted for by Hb changes. Although the primary factor which affects the physical work capacity of iron-deficient anemic subjects seems to be the Hb level, there also seems to be a significant non-Hb related effect of iron treatment as well.
Effects of anemia on serum total cholesterol and triglyceride levels were studied in Sri Lanka. In subjects with hemoglobin (Hb) levels of less than 9.0 g/100 ml, there was a significant relationship between Hb and cholesterol levels (r = 0.53). This relationship was not seen in subjects with Hb levels equal to, or greater than, 9.0 g/100 ml. Triglyceride levels were independent of Hb levels. Total cholesterol levels were elevated following an increase in Hb levels by transfusion and iron treatment. It was suggested that the concentration of red blood cells may affect cholesterol synthesis or mobilization from tissue to plasma.