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Biomedical subjects

L S Eriksson

Publications and source records attributed to L S Eriksson.

67 records · Page 4Linked to original sources

Nitrogen metabolism of the human brain.

Cerebral nitrogen metabolism was studied in 29 healthy nonobese volunteers by means of a catheterization technique. Arterial levels and arterial-jugular venous (A-JV) concentration differences for amino acids, urea, ammonia, 5-oxoproline, glucose, and oxygen were measured in the basal, postabsorptive state and during an intravenous infusion of a commercial amino acid solution. In the basal state positive A-JV differences, indicating a net brain uptake, were noted for 12 of 22 amino acids as well as for ammonia. There was no significant net exchange for urea or for 5-oxoproline. During amino acid infusion, resulting in a 150-300% rise in arterial amino acid levels, the brain uptake of isoleucine, leucine, and tyrosine increased significantly, and a similar tendency was seen for most other amino acids. The infusion was accompanied by a 100% rise in arterial ammonia levels and a 10% increase in urea concentration. For ammonia the small positive A-JV difference in the basal state became markedly greater during amino acid infusion, whereas no significant alteration was noted for urea exchange across the brain. The A-JV differences for glucose and oxygen were positive in the basal state and unchanged during the infusion. The present findings demonstrate that in the basal state (a) there is a significant net brain uptake of most amino acids; (b) no single amino acid, urea, or 5-oxoproline is released from the brain; and (c) ammonia uptake occurs both in this state and during an amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Splanchnic exchange of glucose, amino acids and free fatty acids in patients with chronic inflammatory bowel disease.

In order to study arterial concentrations and splanchnic exchange of substrates and hormones in patients with chronic inflammatory bowel disease three patients with Crohn's disease and four with ulcerative colitis were studied using the hepatic venous catheter technique. Systemic turnover and regional exchange of free fatty acid were evaluated using intravenous infusion of 14C-labelled oleic acid. All measurements were made in the postabsorptive, overnight fasted state. Arterial glucose concentrations were 10% lower in the patients but net splanchnic glucose output was similar in patients and controls. Glucose precursor uptake (lactate, pyruvate, and glycerol), however, was increased two to five fold in the patients. Arterial amino acid concentrations were generally reduced but net splanchnic amino acid uptake was the same in patients and controls. Arterial concentrations of free fatty acid and oleic acid as well as systemic and fractional turnover were similar in patients and controls. The patients' splanchnic uptake of oleic acid was increased more than three fold in comparison with controls. Splanchnic release of oleic acid was also augmented in the patients. Both arterial concentrations and splanchnic production of ketone bodies were raised in the patients. The proportion of splanchnic free fatty acid uptake which could be accounted for by ketone body production was significantly greater in the patients (37 +/- 4%) than the controls (20 +/- 5%, p less than 0.025). Estimated hepatic blood flow was 55% greater (p less than 0.01) in the patients as compared with the controls (1930 +/- 150 vs 1240 +/- 70 ml/min), while splanchnic oxygen uptake was similar in the two groups. From these findings it is concluded that patients with chronic inflammatory bowel disease show (1) markedly increased hepatic blood flow, reflecting an inflammatory hyperaemia in the splanchnic region, (2) a normal net splanchnic glucose output, (3) accelerated hepatic gluconeogenesis as well as ketogenesis, probably as a consequence of the altered hormonal milieau, and (4) low concentrations of most amino acids possibly because of protein malabsorption. These findings underscore the importance of adequate protein and carbohydrate administration to this patient group.

Adult↗

Splanchnic glucose metabolism during leg exercise in 60-hour-fasted human subjects.

An increased mobilization of the hepatic glycogen is necessary for the maintenance of glucose homeostasis during exercise. To examine the effect of exercise on glucose metabolism when the hepatic glycogen stores are depleted, five prolonged-fasted (60-h, PF) subjects were investigated. Arterial concentrations and splanchnic exchange of glucose and gluconeogenic precursors were studied at rest and during exercise (40 min, 60% of VO2max) using the hepatic venous catheter technique. Five overnight-fasted subjects (OF) served as controls. In the resting state, arterial glucose concentration (3.0 +/- 0.2 mmol/liter) and splanchnic glucose output (SGO) (0.3 +/- 0.1 mmol/min) were 30 and 55% lower, respectively, in the PF than in the OF subjects. During exercise SGO rose in both groups, but the increase was smaller in the PF subjects so that at the end of work SGO (0.9 +/- 0.2 mmol/min) was only one-third of that in the OF group (2.5 +/- 0.4 mmol/min). During exercise in the PF state the arterial lactate concentration (5.0 +/- 1.1 mol/liter) and the splanchnic lactate uptake (1.1 +/- 0.3 mmol/min) were threefold and twofold higher, respectively, than in the OF state. In the PF state, the splanchnic uptake of gluconeogenic precursors could account for more than 80% of the splanchnic glucose production both at rest and during exercise. Despite the lower SGO in the PF state, blood glucose concentrations rose during exercise, indicating a diminished peripheral glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravenous infusion of alpha-oxoisocaproate: influence on amino acid and nitrogen metabolism in patients with liver cirrhosis.

1. The metabolic effect of alpha-oxoisocaproate (4-methyl-2-oxovalerate) infusion was examined in six patients with cirrhosis and in nine healthy control subjects. The arterial concentrations of amino acids, urea, ammonia, insulin and catecholamines were determined in the basal state and during intravenous infusion of alpha-oxoisocaproate (300 mumol/min) for 150 min. The exchanges of amino acids and substrates across the splanchnic region, the brain and the leg were examined in the healthy subjects by a catheter technique. 2. Basal alpha-oxoisocaproate levels were similar in patients and control subjects. During infusion the concentrations of alpha-oxoisocaproate rose to 90-130 mumol/l; they were 20-35% lower in the patients. Arterial leucine concentration increased in both groups to 250-300 mumol/l. Valine and isoleucine concentraions decreased (50-60%) as did to a lesser extent the concentrations of aromatic amino acids and methionine. 3. Regional exchange of amino acids was not significantly influenced by alpha-oxoisocaproate infusion. Arterial urea concentration decreased (12%, P less than 0.05) and ammonia levels rose (15-25%, P less than 0.05) in both groups. In the patients both adrenaline (100%, P less than 0.001) and noradrenaline concentrations were elevated (350%, P less than 0.001) in the basal state; insulin levels were similar to those in control subjects. 4. It is concluded that alpha-oxoisocaproate is rapidly transaminated to leucine in patients with cirrhosis and in healthy control subjects. alpha-Oxoisocaproate infusion resembles leucine infusion in its influence on aromatic amino acid concentrations, but in addition it elicits increased ammonia levels and decreased urea formation.

Adult↗

Branched-chain amino acids in the treatment of chronic hepatic encephalopathy.

The therapeutic efficacy of orally administered branched-chain amino acids in patients with liver cirrhosis and chronic encephalopathy was examined in a double blind, randomised crossover study. Seven patients with manifest hepatic cirrhosis and encephalopathy of six months' duration or longer ingested 30 g branched-chain amino acids or placebo during two 14-day periods. Psychometric tests and electroencephalograms were used to evaluate cerebral function. Neither clinical observations nor psychometric testing or electroencephalogram indicated a significant difference in the patients' response to branched-chain amino acids as compared with placebo. In four patients given branched-chain amino acids for longer periods (five to 22 weeks), psychometric tests also remained unchanged. The plasma concentrations of these acids after oral intake increased significantly, demonstrating adequate absorption. Basal plasma amino acid concentrations were unchanged, however, after branched-chain amino acid therapy. No side-effects were seen, which indicates that these amino acids are well tolerated as an extra protein supply in patients with chronic hepatic encephalopathy. As compared with placebo, however, no effect of branched-chain amino acids on the encephalopathy could be detected.

Adult↗

Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study.

The influence of intravenous infusion of branched-chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until "wake up". Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA administration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p less than 0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients. It is concluded that BCAA administration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy.

Acute Disease↗

Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects.

The influence of VIP, a potent vasodilator, on central hemodynamics, splanchnic blood flow and glucose metabolism was studied in six healthy subjects. Teflon catheters were inserted into an artery, a femoral vein and a right-sided hepatic vein. A Swan-Ganz catheter was introduced percutaneously and its tip placed in the pulmonary artery. Determinations of cardiac output, systemic, pulmonary arterial and hepatic venous pressures as well as splanchnic blood flow were made in the basal state and at the end of two consecutive 45 min periods of VIP infusion at 5 and 10 ng/kg/min, respectively. Arterial blood samples for analysis of glucose, FFA, insulin and glucagon were drawn at timed intervals. VIP infusion at 5 ng/kg/min resulted in an increase in cardiac output (55%) and heart rate (25%) as well as a reduction in mean systemic arterial pressure (15%) and vascular resistance (45%). With the higher rate of VIP infusion heart rate tended to rise further while cardiac output and arterial pressure remained unchanged. At 15 min after the end of VIP infusion the above variables had returned to basal levels. Splanchnic blood flow and free hepatic venous pressure did not change significantly. Arterial concentrations of glucose, FFA, insulin and glucagon increased during VIP infusion. At 15 min after the end of infusion the glucose levels were still significantly higher than basal (20%). Net splanchnic glucose output did not change in response to VIP infusion. It is concluded that VIP exerts a potent vasodilatory effect resulting in augmented cardiac output and lowered systemic blood pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hypoxemia in patients with liver cirrhosis.

Chronic liver disease is often accompanied by alterations in the pulmonary and cardiovascular systems as demonstrated by hypoxemia, hyperkinetic circulation and impaired pulmonary and systemic vascular resistance. In some patients these abnormalities are due to ventilation-perfusion imbalance and/or intrapulmonary shunting. Although the pathogenesis of these disturbances is unknown it can be hypothesized that vasodilating substances might bypass the liver and give rise to such changes in intrapulmonary vessels. The normalization of pulmonary perfusion after liver transplantation suggests a direct functional relationship between the liver and the lungs--a "hepatopulmonary syndrome"--similar to the functional renal failure widely known as the hepatorenal syndrome.

Humans↗