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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 289 records · Page 16Linked to original sources
PubMed1985

Assessment of alanine, urea, and glucose interrelationships in normal subjects and in patients with sepsis with stable isotopic tracers.

The kinetic interactions among glucose, alanine, and urea metabolism were studied in both normal volunteers and in patients with sepsis by means of a primed, constant infusion of stable isotopes. In the normal volunteers, infusion of glucose at 4 mg/kg/min suppressed total glucose production, the rate of gluconeogenesis from alanine, and the production of urea, despite an increase in the rate of release and uptake of alanine. When the glucose infusion rate was increased to 8 mg/kg/min, the production of urea decreased further, even though gluconeogenesis from alanine was already suppressed by the first infusion. This additional N-sparing effect was explainable by an increase in glucose oxidation. In the patients with sepsis the basal rates of production of glucose and urea were elevated significantly. Glucose infusion (4 mg/kg/min) decreased hepatic glycogenolysis but not gluconeogenesis from alanine or urea production. At the glucose infusion rate of 8 mg/kg/min, glucose oxidation increased in the patients and urea production decreased. Thus in patients with sepsis a higher rate of glucose infusion is necessary to achieve nitrogen-sparing effects than is necessary in controls because of a lack of suppressibility of gluconeogenesis. Because of continued glucose production during glucose infusion, hyperglycemia commonly develops during glucose infusion in sepsis. However, this effect does not necessarily indicate a complete inability of the patient with sepsis to benefit nutritionally from infused glucose, as we observed no decrement in the ability to oxidize infused glucose.

Adult↗
PubMed1985

Role of very low density lipoproteins in the energy metabolism of the rat.

The role of very low density lipoproteins (VLDL) in the energy metabolism of conscious, 24-hr fasted rats was studied. VLDL labeled with [2-3H]glycerol and [1-14C]palmitate were infused into the rats, along with [1-13C]palmitate bound to albumin and d-8-glycerol, and various metabolic factors were assessed. The rates of appearance in plasma of fatty acids in VLDL and albumin-bound free fatty acids (FFA) were about equal, on a molar basis, and only a small fraction of the FFA flux was derived from VLDL. The rate of direct oxidation of the fatty acids from VLDL was 4.4 +/- 0.9 mumol of FA/kg X min, as compared with the value of 4.0 +/- 0.42 mumol of FA/kg X min for plasma FFA. Four percent of the plasma glycerol flux was derived from VLDL. Thus, the direct oxidation of fatty acids in VLDL played an important role in the energy metabolism of the rats, accounting for a percentage of the total CO2 production that was equal to the amount that arose from the oxidation of plasma FFA. The oxidation of VLDL-fatty acids did not involve prior entry of the fatty acids into the plasma FFA pool to any significant extent.

Animals↗
PubMed1984

Glucose production in the perfused dog liver: effect of free fatty acids and ketones.

The perfused rat liver model has been used widely for the past 30 years to investigate various aspects of hepatic metabolism. Certain aspects of the regulation of glucose production, however, are different in rats and in higher mammals. A method for perfusing dog livers in situ has been developed. It is easier to perform and to standardize than previously described techniques, and enables the direct effect of various substances on glucose production to be tested. This new approach has been used to assess the influence of ketones and albumin-bound free fatty acids (FFA) on total hepatic glucose output. In contrast to the response generally observed in the rat, it was found that an increased availability of FFA or ketones caused a net decrease in glucose output from the dog liver. Thus, perfusion of the dog liver is a feasible technique that is particularly useful because the responses in rats and dogs are not always the same.

3-Hydroxybutyric Acid↗
PubMed1984

Balloon embolization to occlude a Blalock-Taussig shunt.

Balloon embolization was used to successfully occlude a large residual Blalock-Taussig shunt. The use of an "upstream" nondetachable balloon catheter to reduce flow and turbulence during final positioning of the detachable balloon may have made the technique safer and more precise.

Cardiac Catheterization↗
PubMed1984

Inhibitory effect of plasma free fatty acids on glucose production in the conscious dog.

We have previously reported that, in conscious, unrestrained dogs in which insulin and glucagon levels were clamped pharmacologically, combined alpha- and beta-adrenergic blockade resulted simultaneously in a fall in plasma free fatty acid (FFA) levels and an increase in glucose production. In this study we have tested the hypothesis that the increase in glucose production observed in the previous study was due to the fall in plasma FFA concentration. Glucose production was measured by means of the primed-constant infusion of [6-3H]- and/or [U-14C]glucose, and insulin and glucagon were clamped at constant levels by means of the infusion of somatostatin, insulin, and glucagon. When no attempt was made to control the FFA levels, combined alpha- and beta-adrenergic blockade significantly decreased plasma FFA levels, and this was associated with a significant increase in the rate of glucose production. However, the glucose production response to adrenergic blockade was entirely prevented by the clamping of FFA levels at a high, constant value by the infusion of a 10% lipid emulsion (Liposyn) and heparin. We conclude that basal adrenergic activity is important in the mobilization of fat but does not directly influence glucose production. Further, there is an inhibitory effect of FFA on glucose production that is unmasked during hormonal control and alpha- and beta-adrenergic blockade.

Animals↗
PubMed1984

Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs.

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.

3-Hydroxybutyric Acid↗
PubMed1984

Isotopic determination of amino acid-urea interactions in exercise in humans.

We recently reported that in light exercise (30% VO2max) the oxidation of [1-13C]leucine was significantly increased but the rate of urea production was unchanged (J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 52: 458-466, 1982). We have therefore tested three possible explanations for this apparent incongruity. 1) We infused NaH13CO3 throughout rest and exercise and found that, although altered bicarbonate kinetics in exercise resulted in greater recovery of 13CO2, the difference between rest and recovery was small compared with the increase in the rate of 13CO2 excretion during exercise when [1-13C]leucine was infused. 2) We infused [15N]leucine and isolated plasma urea N to determine directly the rate of incorporation of the 15N. During exercise there was no increase in the rate of 15N incorporation. Simultaneously, we infused [2,3-13C]alanine and quantified the rate of incorporation of 15N in alanine. We found that [15N]alanine production from [15N] leucine more than doubled in exercise, and by deduction, alanine production from other amino acids also doubled. 3) We tested our previous assumption that [1-13C]leucine metabolism in exercise was representative of the metabolism of other essential amino acids by infusing [1-13C] and [alpha-15N]lysine throughout rest and exercise. We found that the rate of breakdown of lysine during exercise was not increased in a manner comparable to that of leucine. Thus, these data confirm our original findings that leucine decarboxylation is enhanced in light exercise but urea production is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1984

Effect of substrate intake and physiological state on background 13CO2 enrichment.

The natural enrichment of 13C in energy substrates varies, and this variation must be taken into account when stable isotopic tracers are used in metabolic studies. This is conventionally accomplished by measuring background samples taken before the tracer infusion begins and subtracting these values from postinfusion values. Whereas this approach is satisfactory if no perturbation occurs between the collection of the background samples and the collection of postinfusion sample, the data presented in this paper show that any change in the metabolic state can significantly alter the background enrichment of expired CO2. This study not only confirmed that the introduction of natural energy sources may alter the background enrichment of CO2, but we also found that changes in substrate oxidation induced by different physiological states, such as exercise, can cause significant changes in expired CO2 enrichments. Conclusions from studies in which oxidation of substrates were measured by means of a 13C tracer but potential changes in background enrichments were not accounted for must, therefore, be reassessed.

Animals↗
PubMed1984

Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus.

The effects of 12 wk of physical training in addition to hypocaloric diet (DPT group, N = 10) on body composition, carbohydrate (CHO) tolerance, and insulin secretion and action were compared with the effects of diet therapy alone (D group, N = 8) in CHO-intolerant and non-insulin-dependent diabetic subjects. Fat mass, fat-free mass (FFM), mean fasting plasma glucose, serum C-peptide, and insulin concentrations decreased similarly in both groups. The mean plasma glucose response to a mixed meal decreased approximately 20% in both treatment groups, and, after i.v. glucose, decreased 12% in the D group (P less than 0.05), but did not change in the DPT group (NS between groups). The acute serum insulin response (0-6 min) after IG increased significantly in the DPT group only (NS between groups). The mean basal endogenous glucose production (BEGP) decreased 17% (P less than 0.025) in the DPT group and by 31% (P less than 0.01) in the D group (NS between groups). Hepatic sensitivity to insulin, estimated by BEGP suppression during the euglycemic clamp, increased significantly by 25% in both groups. Total glucose disposal during the euglycemic clamp increased from 3.51 +/- 0.04 milligrams of glucose per kilogram of fat-free mass per minute (mg/kg-FFM/min) to 4.45 +/- 0.54 mg/kg-FFM/min (P less than 0.05) in the DPT group, but no change occurred in the D group (NS between groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Energy and substrate kinetics and oxidation during ketone infusion in septic dogs: role of changes in insulin and glucagon.

We have investigated the response of glucose and free fatty acid (FFA) kinetics and oxidation to betahydroxybutyrate (BOHB) infusion (30 mumol/kg X min) in both normal and Escherichia coli septicemic conscious dogs. In both the septic and control groups, experiments were performed in which hormone levels were allowed to change in response to the BOHB infusion, and in which the infusion of somatostatin, insulin, and glucagon were used to hold those hormone levels constant and sympathetic activity was blocked by the infusion of propranolol and phentolamine. In the nonseptic groups, the infusion of BOHB decreased both glucose production and FFA appearance (RaFFA) independent of the hormonal status. Glucose oxidation decreased in proportion to the decrease in production and uptake. FFA oxidation decreased only when hormones were controlled. In contrast, the infusion of BOHB in septic dogs did not suppress either glucose production or RaFFa, irrespective of the hormonal status. Substrate oxidation again corresponded to the rate of appearance of the substrate. We conclude that in normal dogs, ketones act directly as metabolic regulators to decrease the appearance of both glucose and FFA in the plasma, but do not directly affect the ability of the animal to oxidize these substrates. In sepsis, the normal regulatory actions of ketones appear to be lost.

Animals↗
PubMed1984

A conscious septic dog model with hemodynamic and metabolic responses similar to responses of humans.

We have developed a conscious septic dog model suitable for in vivo tracer studies. Dogs weighing 10 to 20 kg underwent general anesthesia followed by the insertion of long-term arterial, venous, and portal cannulas and the formation of a long-term tracheostomy. After 7 to 10 days of convalescence, the animals were fed in the morning and 4 hours later 10(10) live Escherichia coli organisms were infused intra-arterially over approximately 30 minutes. One hour later a second dose of 5 X 10(9) bacteria was given, again over 30 minutes. Resuscitation was provided by infusion of 1000 ml of lactated Ringer solution over 3 hours. Twenty-four hours after the induction of sepsis the animals were hemodynamically stable and suitable for study. Cardiac output was increased from the control value of 185 +/- 35 ml/kg X min to 308 +/- 44 ml/kg X min in the septic animals. Heart rate was increased from 98 +/- 10 to 125 +/- 5 beats/min, and arterial pressure was not significantly altered. We employed indirect calorimetry and primed constant infusions of both radioactive and stable isotopes to assess a variety of metabolic parameters. The metabolic rate was increased approximately 25%, and the energy for this increase was primarily provided by the increased oxidation of both free fatty acids and triglyceride. The release of free fatty acids was approximately three times greater than the control value, and triglyceride synthesis increased 500%. The oxidation rate of free fatty acids and the fatty acids contained in very low density lipoproteins-triglyceride increased 40% and 900%, respectively. Glucose production was maintained at approximately the control value, and the rate of glucose oxidation (as measured with 14C-glucose) was also not significantly altered. The plasma insulin concentration was moderately elevated, and plasma glucagon concentration was five to six times greater than the control value. Plasma catecholamine levels were increased significantly. This model is suitable for the performance of metabolic studies in sepsis. The induction of a hyperdynamic septic state in less than 24 hours avoids the complications of starvation and dehydration frequently seen in the various peritonitis and abscess models. Most importantly, the model is predictable in its time course and reproducibly creates a situation that hormonally, hemodynamically, and metabolically resembles what is commonly seen in humans with sepsis.

Animals↗
PubMed1983

The measurement of glucose turnover and oxidation using radioactive and stable isotopes.

Isotopes have become the best means for investigating glucose kinetics in vivo. With the recent greater availability of stable isotopes there has developed a need to understand how data may be obtained from the use of both radioactive and stable glucose tracers. Described for the nonexpert is the calculation of glucose appearance and disappearance, clearance and oxidation using both stable and radioactive glucose isotopes, administered both by bolus and primed constant infusion and under both steady and nonsteady state conditions. Other substrates may be studied using similar methodology. The use of stable substrate isotopes will be an expanding field of metabolic research in man.

Glucose↗
PubMed1983

The human metabolic response to chronic ketosis without caloric restriction: physical and biochemical adaptation.

To study the metabolic effects of ketosis without weight loss, nine lean men were fed a eucaloric balanced diet (EBD) for one week providing 35-50 kcal/kg/d, 1.75 g of protein per kilogram per day and the remaining kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD)--isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented with minerals and vitamins. Weight and whole-body potassium estimated by potassium-40 counting (40K) did not vary significantly during the five-week study. Nitrogen balance (N-Bal) was regained after one week of the EKD. The fasting blood glucose remained lower during the EKD than during the control diet (4.4 mmol/L at EBD, 4.1 mmol/L at EKD-4, P less than 0.01). The fasting whole-body glucose oxidation rate determined by a 13C-glucose primed constant infusion technique fell from 0.71 mg/kg/min during the control diet to 0.50 mg/kg/min (P less than 0.01) during the fourth week of the EKD. The mean serum cholesterol level rose (from 159 to 208 mg/dL) during the EKD, while triglycerides fell from 107 to 79 mg/dL. No disturbance of hepatic or renal function was noted at EKD-4. These findings indicate that the ketotic state induced by the EKD was well tolerated in lean subjects; nitrogen balance was regained after brief adaptation, serum lipids were not pathologically elevated, and blood glucose oxidation at rest was measurably reduced while the subjects remained euglycemic.

Acidosis↗
PubMed1983

A model for isotopic sampling and administration in constant infusion experiments: a test with 13C-palmitate.

We have proposed and tested a model that demonstrates the importance of the site of isotopic sampling relative to the site of infusion for the constant infusion of labeled palmitate. Palmitate enrichment is significantly increased downstream from the infusion catheter. However, palmitate production is underestimated unless sampling is performed upstream from the catheter. There was no significant difference between upstream sampling from the femoral vein versus the right heart, whereas the downstream arterial sampling gave significantly higher enrichments compared to the femoral vein. We have also discussed the importance of sampling sites for other substrates and the constraints that this model places on the design and interpretation of whole body primed constant infusion experiments using labeled substrates.

Animals↗
PubMed1983

Response of protein and urea kinetics in burn patients to different levels of protein intake.

The effects of two levels of protein intake on protein metabolism in six severely burned adult patients were studied (means of 70% BSA burned). A crossover experimental design enabled the authors to study each patient at the end of two three-day dietary regimens. All diets were isocaloric and provided approximately 25% more calories than the measured energy expenditure (means = 40.8 Kcal/kg X day). In one regimen, each patient received 2.2 g protein/kg X day, while during the other treatment period they received 1.4 g protein/kg X day. The patients were studied in the fed state and after 10 to 12 hours of fasting. Leucine kinetics were determined by means of the primed-constant infusion of [1--13C]--leucine. The authors were able to distinguish the oxidation of plasma leucine from the oxidation of leucine derived from intracellular protein at the site of the deamination of leucine (predominantly muscle) by simultaneously determining both leucine and alpha-ketoisocaproic acid enrichment. Also, rates of whole-body protein synthesis and catabolism were calculated from the leucine flux and oxidation data. Net protein synthesis was also calculated by means of another stable-isotope technique involving the infusion of [15N2]--urea. Finally, a third means of estimating net protein catabolism based on urinary N-excretion data was used at the same time that the isotopic studies were performed. The 13C leucine-data and the N-excretion data indicated that a balance between protein synthesis and catabolism could be achieved with a protein intake of 1.4 protein/kg X day. When protein intake was increased to 2.2 g protein/kg X day, neither isotopic method indicated a further beneficial effect on net protein synthesis, although the absolute rates of protein synthesis and catabolism were stimulated. The N-excretion data, on the other hand, indicated a significant improvement in net protein synthesis with higher protein intake. Regardless of the level of protein intake, the underlying alterations in protein metabolism that occurred as a response to burn injury persisted.

Adolescent↗