Inert gas rebreathing: the effect of haemoglobin based pulmonary shunt flow correction on the accuracy of cardiac output measurements in clinical practice.

BACKGROUND: Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non-invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (Q(S)). A reliable shunt correction requiring the haemoglobin concentration (c(Hb)) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to Q(S) correction on the accuracy of IGR. METHODS: Cardiac output determined by cardiac magnetic resonance imaging (CMR) served as reference values. The data was analysed in four groups: PBF without correcting for Q(S) (group A), shunt correction using the patients' individual c(Hb) values (group B), a fixed standard c(Hb) of 14.0 g dl(-1) (group C) and a gender-adapted standard c(Hb) for male (15.0 g dl(-1)) and female (13.5 g dl(-1)) probands each (group D). RESULTS: 147 patients were analysed. Mean CO(CMR) was 5.2 +/- 1.4 l min(-1), mean CO(IGR) was 4.8 +/- 1.3 l min(-1) in group A, 5.1 +/- 1.3 in group B, 5.1 +/- 1.3 l min(-1) in group C and 5.1 +/- 1.4 l min(-1) in group D. The accuracy in group A (mean bias 0.5 +/- 1.1 l min(-1)) was significantly lower as compared to groups B, C and D (0.1 +/- 1.1 l min(-1); P<0.01). CONCLUSION: IGR allows a reliable non-invasive determination of CO. Since PBF significantly increased the measurement bias, shunt correction should always be applied. A fixed c(Hb) of 14.0 g dl(-1) can be used for both genders if the exact c(Hb) value is not known. Nevertheless, the individual value should be used if any possible.

[Alternative and complementary therapies in multiple sclerosis]. / Alternative und komplementäre Therapien der Multiplen Sklerose.

Most MS patients use unconventional therapies, usually as complementary measures in addition to the conventional treatment. Only a few adequate clinical trials exist in this field. By definition, the efficacy of these therapies is unproven. Moreover, the possible risks are also largely unknown. Some therapies rely on rational pathophysiological considerations, other must be regarded as potentially harmful. The influence of diet on MS is unproven. Possibly, unsaturated fatty acids are beneficial. However, a few randomized trials yielded inconclusive results. Long-term supplementation of Vitamin D is associated with a decreased MS incidence. There is, however, insufficient evidence for an influence of Vitamin D on the course of the disease. Because of the high prevalence of osteoporosis in MS patients, prophylaxis with Vitamin D and Calcium is widely accepted. The effects of various minerals, selenium, antioxidant compounds, fish oil or vitamins remain speculative. Many patients use cannabis to alleviate spasticity and pain. Small series indicated positive effects, but randomized trials were negative for spasticity. However, many patients report subjective improvement under cannabis even if their objective parameters remain unchanged. Hyperbaric oxygenation was the subject of several small studies with heterogeneous results which, overall, do not support its use. Generally, physical therapies are perceived as an established therapy for MS. Short-term effects are probable, whereas the possible favourable long-term effects are unclear.

[Diet and multiple sclerosis]. / Multiple Sklerose und Ernährung.

Beneficial effects from any particular diet have not been proven in multiple sclerosis (MS). Therefore, the general guidelines on nutrition should be followed. Obesity and various forms of malnutrition worsening the MS symptoms are frequently observed. There is some evidence from epidemiological studies that a high consumption of saturated animal fat is associated with an increased incidence of MS. The findings from such studies indicate that supplementation with unsaturated fatty acids, in particular omega-3 fatty acids, could positively influence the course of MS. However, controlled studies did not show clear beneficial effects from polyunsaturated fatty acids. The intake of vitamin D is associated with a lower incidence of MS. In contrast, the effects of therapy with vitamin D on the course of MS have not been ascertained. Patients with MS carry an enormous risk of osteoporosis, and therefore the indication for a preventive therapy with vitamin D and calcium should be established in every postmenopausal woman or after repeated steroid treatments.

Hyperammonemia-induced depletion of glutamate and branched-chain amino acids in muscle and plasma.

BACKGROUND/AIMS: Exogenous hyperammonemia is known to decrease the plasma levels of branched-chain amino acids (BCAA). To investigate whether changes in intracellular amino acid concentrations of muscle are associated with and may, at least in part, mediate this effect, experiments were carried out on a total of 60 male Wistar rats. METHODS: Five groups were formed in a randomized manner. Group A: no treatment; groups B1 and B2: 2-hour and 6-hour continuous central-venous infusions, respectively, of sodium salts; groups C1 and C2: 2-hour and 6-hour infusions of ammonium salts. We obtained venous blood samples and muscle biopsies. Plasma ammonia, whole blood glucose, serum insulin, blood pH, and amino acids in plasma as well as in the intracellular water of muscle were measured. RESULTS: As compared with control group A, groups C1 and C2 displayed a 3.3- and a 4-fold increase, respectively, in the plasma ammonium concentration. Regarding insulin, the ammonium-infused rats were similar to group A but not to the sodium-infused B groups, which had significantly lower insulin concentrations. Administering ammonium brought about a decline in BCAA concentrations in plasma after 2 hours and in muscle after 6 hours. The ammonium-induced fall in intracellular BCAA values was preceded by an increase of glutamine as well as by a decrease of glutamate and alanine in both plasma and muscle. CONCLUSIONS: It is pointed out that the inter-group differences in serum insulin, although possibly accounting for some of the findings, can by no means explain the entire pattern of amino acid concentrations seen after the ammonium infusions. Instead, our results agree with the hypothesis that hyperammonemia indirectly lowers the plasma levels of BCAA by stimulating glutamine synthesis, thus reducing the intracellular glutamate pool, which is likely to be restored, at least in part, by an intensified BCAA transamination. Clarification is needed as to whether carbon skeletons derived from valine and isoleucine additionally contribute to replenishing the glutamate pool.

Substrate balances across colonic carcinomas in humans.

To investigate the utilization of nutrients by malignant tumors in humans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, which was also used for determining tumor blood flow (direct venous outflow technique). Additionally, the substrate exchange by peripheral tissues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There was a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the malignancies exceeded the peripheral exchange rates 30- and 43-fold, respectively (mean values different at P < 0.001). The molar ratio of lactate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The carcinomas utilized branched chain amino acids and serine, while alanine and, in particular, ammonia were released in large amounts. Net glutamine retention was not consistently observed. It is concluded that the energy metabolism of human colonic carcinomas relies predominantly on glucose, with fat-derived calories making no appreciable contribution. The impaired nutritive perfusion of malignant tumors appears to favor glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessment of trans-tumor substrate flux rates is a workable and valid model for analyzing metabolic balances across human colonic cancers in vivo.

The interplay between nutrition and body composition.

Stress and malnutrition are associated with altered body composition. Extracellular fluid increases, with wt gain, but in response to stress BCM may gradually shrink with wt loss. In catabolic illness there is extracellular fluid expansion and erosion of AT and BCM. In stress, net loss of body fat was associated with interstitial accumulation of lipids preferentially in muscle, although BIA did not indicate increased fat and decreased water. Severe trauma and sepsis exerted prolonged effects on tissue electrolyte and water metabolism. Treatment of the critically-ill is of the primary illness. Nutritional therapy is an effective adjunct except in chronic sepsis or critical patients with MOF with great wt and protein loss. Glutamine dipeptides may help with cellular hydration and address catabolic changes.

Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design.

This paper documents dose-dependent effects of ornithine aspartate (OA) on postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis were randomized to undergo 1 out of 4 infusion series. Each series consisted of four 8-h infusions (09:00 h-17:00 h), with placebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate days in varying sequences. This 4-fold crossover design was double-blind. On infusion days, patients received 2 oral protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood samples were drawn every 2 h and the 24-h urine was collected. In addition to measuring plasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in the ammonia concentration was noted during the infusions of placebo and 5 g of OA but did not occur with the dosages of 20 g (after the second protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammonia after the minor protein load. Urea production rate increased when 20 g or 40 g of OA was administered. Of the amino acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate showed a rise in its plasma level following infusion of 40 g of OA, whereas glutamine did not. Concentrations of methionine, phenylalanine, tyrosine, threonine, serine and glycine declined progressively with increasing doses of OA (5-40 g). The highest dose of the drug caused hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodilution in acute ischaemic stroke comparison of two haemodilution regimen.

In a prospective study we randomly allocated 50 patients with acute ischaemic stroke in the area of the middle cerebral artery within 12 hours after onset to two moderate hypervolemic haemodilution regimen consisting of 500 ml of 10% hydroxyethyl starch per day for 10 days. In the high haematocrit group the target haematocrit of 41-42% was achieved by 0-3 phlebotomies and additional replacement of that volume with the colloid in 3 days. In the low haematocrit group with 1-4 phlebotomies a target haematocrit of 37-38% was reached in 4 days. The groups did not differ regarding age, risk factors, haematocrit and neurological score. The improvement of the disturbed blood rheology was more pronounced in the low haematocrit group. One death occurred in each group. The neurological score showed a significantly greater increase in the low haematocrit group with +59% at day 5 and +125% at day 11; the data for the high haematocrit group were +34% and +89% respectively. We calculated a correlation (r = 0.36, p less than 0.02) between the rise in neurological score and the reduction of haematocrit. Our data suggest but not do prove that an early start on moderate hypervolemic haemodilution is beneficial in patients with acute ischaemic stroke and disturbed blood rheology.

Intra- and extracellular amino acid concentrations in portacaval-shunted rabbits. Role of hyperammonemia and effects of branched-chain amino acid-enriched parenteral nutrition.

Intra- and extracellular amino acid concentrations were measured in rabbits in order to elucidate the possible role of hyperammonemia in lowering the postabsorptive plasma levels of branched-chain amino acids (BCAA) and to assess the effects of BCAA-enriched total parenteral nutrition (TPN) on the amino acid pattern of muscle. The pathophysiological part of this paper deals with portacaval anastomosis (PCA) and is aimed at substantiating or rejecting our hypothesis that excessive ammonia-by stimulating glutamine synthesis-reduces the intracellular glutamate pool which is then restored, at least in part, by an intensified BCAA degradation. Regarding infusion therapy, we were mainly interested in whether an amino acid solution adapted to the metabolism in liver cirrhosis causes an accumulation of BCAA in muscle or modifies the intracellular content of glutamate and glutamine. Eighteen rabbits did not undergo surgery and served as controls (group A), while 30 were given a portacaval end-to-side anastomosis (group B). Two weeks after creating the PCA, venous blood samples were taken and muscle biopsies (Bergström's technique) were performed postabsorptively. An 18-h TPN was then started, the regimen administered included dextrose, fat and, in addition, either a conventional (group B1, n = 15) or an adapted amino acid solution (group B2, n = 15). We obtained second blood specimens and muscle biopsies at the end of the infusion period. With the control animals, the same time schedule for blood sampling and muscle biopsies was followed. Fourteen days after the operation, the PCA rabbits displayed a mean plasma ammonia level 5.1 times higher than that measured in the controls (p less than or equal to 0.001). Conventional blood chemistry did not reveal any impairment of liver cell integrity or over-all hepatic function, whereas the nutritional state of the shunted animals worsened, as indicated by body weight and biochemical variables. Since in the PCA rabbits, the total amino acid pools of muscle and plasma were seen to be increased and decreased, respectively, the results concerning the individual amino acids are given in terms of both the absolute and percentage values, the latter more often revealing high levels of statistical significance. PCA induced a marked rise in the intra- and extracellular concentrations of glutamine, while the values of glutamate and alanine showed a decline in muscle and plasma. The extracellular levels of methionine, phenylalanine, and tyrosine were raised, while those of the BCAA were diminished.(ABSTRACT TRUNCATED AT 400 WORDS)

[Effect of hemodilution with 10% hydroxyethyl starch solution (MW 200,000/9.5) on the flow properties of blood, arterial blood gases and conjunctival oxygen partial pressure in patients with cerebral infarct]. / Einfluss einer Hämodilution mit 10% iger Hydroxyäthylstärkelösung (MW 200,000/0,5) auf die Fliesseigenschaften des Blutes, die arteriellen Blutgase und den konjunktivalen Sauerstoffpartialdruck bei Patienten mit Hirninfarkt.

Hemorheological parameters, arterial blood gases and conjunctival oxygen tension were measured in 15 patients with acute ischemic stroke and compared with values obtained in an age matched reference group. Since the conjunctival capillary bed is perfused by the ophthalmic artery, it reflects the oxygen delivery to the areas supplied by the internal carotid artery. Measurements of conjunctival oxygen tension are simple and safe. Patients with acute ischemic stroke showed a lowered conjunctival oxygen tension; this holds true especially to the ipsilateral side, i.e. the side where the attack occurred, and to a lesser extent to the other side. By contrast, the ratio of arterial/conjunctival pO2 was disturbed only on the ipsilateral side. Furthermore, these patients had pathologically elevated values for red cell aggregation, whole blood and plasma viscosity. After infusing 500 ml 10% middle-molecular-weight hydroxyethyl starch (10% HAES-steril) and phlebotomy (250 ml) blood fluidity was normalized, although the hematokrit was only slightly reduced. Arterial pO2 improved slightly while pCO2 remained unchanged. Conjunctival oxygen tension improved by 30% on the ipsilateral and by 10% on the contralateral side, the ipsilateral values always remaining significantly lower. The ratio conjunctival/arterial pO2 raised only on the ipsilateral side where it was below the reference range before hemodilution. In addition to the well known improvement of blood fluidity and augmentation of cerebral blood flow following hemodilution in patients with acute ischemic stroke, there seems to be an increase in oxygen supply in the territories of both internal carotid arteries, especially on the ipsilateral side as indicated by the values of conjunctival oxygen tension and the ratio of conjunctival to arterial pO2.

[Intracellular amino acid concentrations in the musculature of 3 species of animals under physiologic, pathophysiologic and infusion therapy conditions]. / Intrazelluläre Aminosäurenkonzentrationen der Muskulatur dreier Tierspezies unter physiologischen, pathophysiologischen und infusionstherapeutischen Bedingungen.

In the first part of this paper methodological aspects of intracellular amino-acid analysis in three species of animals, i.e. in rats, rabbits, and cats are dealt with. The genetic homogeneity as well as the age of the animal groups, metabolic differences between carnivores and herbivores, the length of the intestine and, thus, the time elapsing before the postabsorptive state is reached, furthermore, the body size which, in studies with muscle biopsies, makes correlated samples either possible or impossible; all these factors are experimental variables potentially affecting the evidence of the results obtained. Amino acids being involved in ammonia detoxification or showing raised plasma levels in hepatic failure form the subject of the subsequent parts of this paper. In the muscle cells of the three above species investigated after an overnight fast, the concentration of glutamine was about 5.5 times and that of glutamate about 4.1 times higher than in human muscle. Regarding glutamine and glutamate, there were no marked differences between the three species. As to the other amino acids measured in the rats, rabbits, and cats, alanine, the branched-chain amino acid (BCAA) as well as methionine and phenylalanine had intracellular values similar to those observed in humans. To test the hypothesis that ammonia lowers the BCAA plasma levels by considerably increasing glutamine synthesis and decreasing the intracellular glutamate pool with consecutively intensified transamination of BCAA for partial replenishment of this pool, we infused ammonium salts and created portocaval shunts in animal experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

[Amino acid uptake and release by colorectal cancer in man]. / Aminosäurenaufnahme und -abgabe kolorektaler Karzinome des Menschen.

Little information is available regarding the amino acid exchange by human tumors. To characterize this exchange in vivo, 21 patients with resectable colorectal carcinomas were studied during curative operations. Concerning the amino acid uptake and release by peripheral tissues, 20 non-cancer patients served as controls. Both groups of subjects were well-nourished, as indicated by anthropometric and biochemical variables. In the cancer patients, we cannulated a peripheral artery and vein as well as a central tumor-draining vein and the portal vein. Plasma concentrations and concentration differences were determined in mumol/l and in percentages of the total amino acid amounts. Peripheral glutamate uptake per liter plasma was reduced in the cancer patients (p = 0.02). In these patients, the central tumor-draining vein contained less glutamine (p = 0.002) and more glutamate (p = 0.002) than the peripheral vein. Glutamine uptake by the tumor occurred more often than glutamine release, while glutamate had a negative balance across the tumor in all but three cases. The qualitative differences between the peripheral tissues and the tumors with respect to glutamine and glutamate exchange reached high levels of significance (p = 0.002 for both of the amino acids). In addition, the tumors released more glycine, ornithine, and tyrosine than the periphery. As to glutamine and glutamate metabolism, there was a significant difference between the tumors and the portal-drained organs (p greater than or equal to 0.05). The discussion of the results emphasizes the contributions made by the periphery and the tumor to the plasma amino pattern. The role of glutamine as a potential high importance energy source for neoplastic tissues is delineated.

[A new micromethod for the determination of ammonia concentrations in whole blood and plasma]. / Eine neue Mikromethode zur Bestimmung der Ammoniakkonzentration im Vollblut und Plasma.

Ammonia concentrations were measured in 152 plasma samples taken from patients with liver cirrhosis or from intensive care patients. For each sample, a new reflectometric procedure (AC-System) as well as the enzymatic method (Monotest) were used. There was a high and significant correlation between the values obtained with the two methods (r = 0.98, p less than or equal to 0.001). Ammonia determination by means of the reflectometric procedure can also be done in whole blood.