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Biomedical subjects

L Jorfeldt

Publications and source records attributed to L Jorfeldt.

At least 19 recordsLinked to original sources

Randomized, controlled study evaluating effects of branched chain amino acids and alpha-ketoisocaproate on protein metabolism after surgery.

The effect of nutritional supplementation with branched chain amino acids or the ketoacid alpha-ketoisocaproate on protein metabolism after surgery was studied in 24 patients with gastrointestinal cancer. They were randomized to receive one of three nutritional regimens. All patients received a balanced amino acid solution and group 1 (n = 8) received no further supplements, group 2 (n = 8) received supplementation with alpha-ketoisocaproate (17 g day-1) and group 3 (n = 8) received a branched chain solution including leucine, isoleucine and valine, corresponding to 3.3 g nitrogen day-1. Plasma albumin, prealbumin, fibronectin and serum urea concentrations, nitrogen balance and 3-methylhistidine release from the leg and its excretion in the urine were measured. Albumin and prealbumin concentrations fell after surgery in all groups, and fibronectin levels fell in group 2 (P less than 0.001). In group 2 there was also a significant increase in serum urea concentration after operation (P less than 0.05). Cumulative nitrogen balance after 3 days was -5.6 g (group 1), -3.8 g (group 2) and -1.7 g (group 3). The release of 3-methylhistidine (nmol 100 g-1 min-1) from the leg after operation, following an overnight fast, was -0.42 (group 1), -0.51 (group 2) and -0.66 (group 3). During infusion the release was -0.56, -0.99 and -0.81, respectively. A balanced amino acid solution with an adequate energy supply has an optimal nitrogen-sparing effect. Branched chain amino acids or alpha-ketoisocaproate did not improve nitrogen balance or reduce protein degradation.

Amino Acids, Branched-Chain

Gas exchange as monitored in mixed venous and arterial blood during experimental cardiopulmonary resuscitation.

Nineteen anaesthetized piglets were investigated. After catheterization and a stabilization period, ventricular fibrillation was induced with a transthoracic DC shock, after which a 10-min period of cardiopulmonary resuscitation (CPR) took place. CPR included manual chest compression and mechanical ventilation with pure oxygen. After 1 min of CPR, an infusion of alkaline buffer was begun and completed within 5 min. A total of 50 mmol of either sodium bicarbonate (n = 6) or tris buffer mixture (n = 7) were given. These two groups were compared with a third control group (n = 6) receiving the same volume of normal saline. After 8 min of CPR all animals were given 0.5 mg adrenaline i.v., and after 10 min DC shocks were used to revert the heart back to normal sinus rhythm. Our results demonstrate that blood flow and not ventilation is the limiting factor for the efficient disposal of CO2 during CPR. This also applied when the demand for CO2 transport was increased by administration of sodium bicarbonate. The respiratory exchange ratio increased 1.9-fold, indicating that the transport of carbon dioxide was less affected than that of oxygen. The estimated alveolo-arterial oxygen tension difference, shunt, and overall ventilation/perfusion ratio increased, creating an inverse hyperbolic relationship between arterial PCO2 and PO2. The difference between mixed venous and arterial PCO2 correlated well to the mixed venous PCO2, implying more efficient pulmonary elimination of PCO2 when the mixed venous PCO2 was high. Pulmonary gas exchange during CPR appears to be independent of alkaline buffer therapy in the form of sodium bicarbonate or tris buffer mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus.

Improved blood glucose control by insulin treatment in patients with Type 2 (non-insulin dependent) diabetes mellitus increases the risk for hypoglycaemic episodes. Our objective was to investigate if hypoglycaemia causes electrocardiographic changes and cardiac arrhythmias in patients with Type 2 diabetes. Six insulin-treated patients with Type 2 diabetes and no known cardiac disease took part in the study. Hypoglycaemia was induced by insulin infusion aiming at a plasma glucose less than or equal to 2.0 mmol l-1 or hypoglycaemic symptoms. All patients experienced hypoglycaemic symptoms. The median lowest arterial plasma glucose was 2.0 mmol l-1. Arterial plasma adrenaline concentration increased from 0.4 +/- 0.1 (mean +/- SE) to 6.9 +/- 0.3 nmol l-1 (p less than 0.001) while serum potassium was lowered from 4.1 +/- 0.3 mmol l-1 to 3.5 +/- 0.2 mmol l-1 (p less than 0.001). The heart rate increased significantly during hypoglycaemia except in one patient who developed hypoglycaemic symptoms and a severe bradyarrhythmia at a plasma glucose of 4.4 mmol l-1. One patient developed frequent ventricular ectopic beats during hypoglycaemia while four patients showed no arrhythmia. ST-depression in ECG leads V2 and V6 was observed during hypoglycaemia in five patients (p less than 0.05) and four patients developed flattening of the T-wave. In conclusion, the study supports the hypothesis that hypoglycaemia in patients with Type 2 diabetes may be hazardous by causing cardiac arrhythmias.

Arrhythmias, Cardiac

The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis.

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.

2-Chloroadenosine

Absorption of irrigating fluid during transurethral prostatic resection as measured by ethanol, radioisotopes, and regular-interval monitoring.

Ethanol monitoring is a novel noninvasive method for immediate detection of absorption of irrigating fluid during transurethral prostatic resection. Its accuracy was evaluated during thirteen resections using 5% mannitol +2% ethanol as the irrigating fluid. The ethanol concentration in the expired breath correlated strongly with the degree of absorption of intravascular irrigating fluid as determined by a radioisotope technique, and fluid volume measurements, and with the changes in the serum sodium concentration. Extravascular absorption of the irrigating fluid resulted in prolonged elevation of the ethanol concentration and gave smaller changes in the serum sodium concentration.

Absorption

Use of ethanol as marker substance to increase patient safety during transurethral prostatic resection. Screening investigation of irrigating fluid absorption in four hospitals and comparison of experienced and inexperienced urologists.

Of 472 patients at four different hospitals electively undergoing transurethral resection of the prostate (TURP), 192 received Sorbitur as an irrigating fluid with 2% ethanol (w/v) as a marker. Using a breath analyzer (Alcol-meter), the amount of ethanol in expired air was measured regularly during the operation to detect the absorption of irrigating fluid. The ethanol concentration in expired air was plotted against time. The time-ethanol concentration product was used as a measurement of absorbed ethanol marked irrigating fluid. A unit of more than 2.5 was considered to be a major absorption with possible clinical significance. This criterion was fulfilled in 24 percent of the patients. Postoperative serum sodium was shown to decrease more in patients with major absorption than in patients with minor absorption in comparison to preoperative values. The weight of resected tissue and the bleeding per resected gram of tissue was higher in the patients with major absorption, but the resected tissue per operating time was the same in both groups. The experienced urologists had as many patients with absorption as did the inexperienced ones. Ethanol-marked irrigating fluid is a simple, safe, noninvasive, rapid, and cheap method of detecting absorption of irrigating fluid thus increasing patient safety during TURP. This method indicates absorption before clinical signs and symptoms of the TUR syndrome occur. It also provides an easy method for estimating the frequency of absorption of irrigating fluid routinely in clinical work.

Absorption

Delayed recovery of muscle pH after short duration, high intensity exercise in malignant hyperthermia susceptible subjects.

Six subjects susceptible to malignant hyperthermia (MHS) and seven control subjects exercised for 4 min at 120% of their calculated maximal oxygen uptake on a bicycle ergometer. Mean (SEM) muscle pH, measured with a needle-tipped electrode in the vastus lateralis muscle, decreased from a resting value of 7.16 (0.04) to 6.78 (0.04) after exercise in the control group, and from 7.15 (0.05) to 6.56 (0.05) in the MHS group (P less than 0.01 compared with control group). A further decrease in muscle pH to 6.68 (0.06) by 5 min after exercise occurred in the control group, followed by incomplete recovery to 7.06 (0.04) 30 min after exercise. In the MHS group, however, muscle pH decreased to 6.45 (0.05) 5 min after exercise before recovering slowly to only 6.64 (0.07) after 30 min (P less than 0.01 compared with control group). There was no difference in muscle temperature, venous pH or venous lactate concentrations between the two groups. The results show that there is abnormal recovery of muscle pH after short-duration, high-intensity exercise in MHS subjects.

Adult

Effect of hemodilution on maximal oxygen consumption, blood lactate response to exercise and cerebral blood flow in subjects with a high-affinity hemoglobin.

10 subjects with Hb Linköping (beta 36 Pro greater than Thr), a high-affinity hemoglobin variant, with a P50 of 2.2 kPa (16.5 mm Hg) were investigated before and 3-4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 +/- 13 (SD) to 146 +/- 15 g l-1 and the red cell volume from 2.77 +/- 0.83 to 2.23 +/- 0.67 l. Maximal oxygen consumption decreased slightly by 2.7 +/- 3.8 ml min-1 kg-1 and maximal exercise power by 11 +/- 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (-1.1 +/- 6.4 beats min-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 +/- 10.3 ml min-1 100 g-1 from before to after hemodilution. The results indicate that subjects with Hb Linköping have only limited benefit from their increased blood hemoglobin concentration.

Adult

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.

Aconitate Hydratase

Pre- and postprandial hyperinsulinemia during insulin pump treatment; role of the subcutaneous bolus and basal infusion.

The impact of the bolus dose and the basal infusion during insulin pump treatment on pre- and post-prandial hyperinsulinemia was investigated in 8 insulin-dependent diabetic patients. Frequent determinations of free insulin in blood and simultaneous determination of glucose consumption with euglycaemic clamp technique were made after a bolus of 5 U with or without basal infusion and after 10 U with basal infusion. The maximum free insulin level was reached after 75, 65 and 105 min respectively (median; NS), whereas 50% of the maximum was reached already after 15, 10, and 12.5 min (NS). The fall in free insulin after the peak was slower in all protocols compared to the breakfast induced peak in healthy subjects and it was slower with than without basal infusion (p less than 0.03). Glucose consumption followed the free insulin profiles. We conclude, that administration of a subcutaneous bolus with an insulin pump gives a dose-related free insulin peak that is unphysiological in comparison with the normal meal-related insulin secretion. Preprandial hyperinsulinemia, found after a prescribed interval of 30 min between injection and meal, as well as postprandial hyperinsulinemia, increased with a greater bolus indicating that adjustments of timing of meals and snacks may be necessary when the dose is changed. Furthermore, the insulin substitution with external pumps would probably be more physiological if the basal supply was interrupted after a bolus.

Adult

Comparison of dye-dilution and plethysmographic blood flow measurements: an evaluation of the influence of invasive techniques on blood flow and on arterial and femoral venous substrate variables in man.

1. In eight healthy volunteers we compared leg blood flow, as determined in a calf segment by strain-gauge plethysmography, with the flow measured by a constant-rate infusion of Indocyanine Green dye into the femoral artery. The representativeness of the calf segment was evaluated by complementary measurements with additional strain gauges attached around the proximal and distal crural and the distal thigh segments (n = 6). Furthermore, we investigated the influence of the catheterization procedure and a simulated vascular puncture, as well as repeated venous occlusions, on blood flow and on arterial and femoral venous substrate concentrations and blood gases (n = 8). 2. The leg blood flow measured by dye dilution was 0.31 +/- 0.03 litre/min (mean +/- SEM). The blood flow in the calf segments was 14.8 +/- 1.6 ml min-1 litre-1 and no difference between the legs was observed. Extended to the whole leg the plethysmographic blood flow was 0.17 +/- 0.01 litre/min and thus lower (43 +/- 7%, P less than 0.001) than the flow determined by the indicator-dilution method. Blood flow in the legs was not influenced by catheterization or sham punctures of the vessels or by repeated venous occlusions. 3. The concentrations of glucose, lactate and glycerol, as well as blood gas variables, in arterial and femoral venous blood did not change during the study or decreased so slightly (pH and lactate) that the arteriovenous difference was not influenced. 4. We conclude that the blood flow of the total leg cannot be satisfactorily estimated from strain-gauge plethysmography of a single calf segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Influence of local beta-adrenoceptor blockade on exchange of fat and glucose in the human leg after surgery.

The metabolic effects of the local administration of propranolol were determined in seven patients undergoing cholecystectomy. Measurements were carried out in the early postoperative period before and after infusion of 2 mg of intraarterial propranolol into the femoral artery of one leg using the other leg as control. Blood flow and arterio-venous concentration differences for oxygen, glucose, lactate, alanine, glycerol and total FFAs were determined. Uptake and release of FFAs were determined by using a tracer technique. The statistical analyses were based on differences between the test and the control leg in changes following the blockade. Glycerol release was significantly more suppressed in the test leg than in the control leg. No difference between the legs was seen in the uptake of oxygen, FFA and glucose or the release of lactate and alanine. The arterial concentration of propranolol was 6.07 +/- 0.72 ng ml-1 (mean +/- SEM). This study indicates that a local beta-blockade by intra-arterial propranolol infusion after surgery slightly reduces the postoperative lipolysis in leg tissues but does not influence or only marginally influences leg blood flow and oxygen uptake or the exchange of glucose, lactate and alanine after moderate surgical trauma.

Adult

Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease.

Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.

Acetylcarnitine

Blood fuel metabolites at rest and during exercise in patients with advanced chronic obstructive pulmonary disease with and without chronic respiratory failure.

Eighteen patients with advanced chronic obstructive pulmonary disease (COPD), 8 with chronic respiratory failure (CRF group) and 10 without (NCRF group) were investigated using arterial blood analyses before, during and after progressive exercise. Dynamic spirometry was also performed. The arterial blood was analyzed for free fatty acids (FFA), glycerol, 3-hydroxybutyrate, alanine, glucose and lactate concentrations as well as PO2 and PCO2. In the CRF group the concentrations of FFA, glycerol and 3-hydroxybutyrate were lower and the concentrations of glucose and lactate higher than in the NCRF group. Analysis of the whole material revealed that the arterial FFA, glycerol and 3-hydroxybutyrate concentrations correlated positively to arterial PO2 and negatively to arterial PCO2 at rest, as well as during exercise and recovery. The results indicate that lipolysis is decreased in patients with advanced COPD with chronic respiratory failure. An altered glucose metabolism may also exist in these patients.

3-Hydroxybutyric Acid

Skeletal muscle metabolites and fibre types in patients with advanced chronic obstructive pulmonary disease (COPD), with and without chronic respiratory failure.

Eighteen patients with advanced COPD, 8 with chronic respiratory failure (RF) and 10 without (nonRF, NRF) were investigated using spirometry, arterial blood gas analysis and biopsies taken from the quadriceps femorls muscle. The biopsies were analysed for ATP, creatine phosphate (CrP), creatine (Cr), lactate and glycogen content. Muscle fibre composition was also studied. Low concentrations of ATP, glycogen and CrP were found in the RF patients. Significant correlations were found between muscle metabolites and arterial blood gas values with the strongest correlation between muscle glycogen and arterial PO2 (r = 0.70; p less than 0.001). A very low percentage of "oxidative" type I muscle fibres was found in both groups. Possible mechanisms causing depletion of muscle metabolites are discussed.

Adenosine Triphosphate