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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 91 records · Page 5Linked to original sources
PubMed1998

Albumin synthesis after intense intermittent exercise in human subjects.

We measured hepatic albumin synthesis in five volunteers (4 men and 1 woman) at 3 and 6 h after recovery from intense exercise. A primed-constant infusion of a stable isotopic tracer of phenylalanine was used to determine hepatic fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin from the enrichment of phenylalanine in albumin. The infusion of the stable isotope tracer began 2 h after upright exercise or upright rest. Albumin FSR and ASR were 6.39 +/- 0.48%/day and 120 +/- 9 mg.kg body wt-1.day-1, respectively, 3-6 h after recovery from exercise; the FSR and ASR on the time control study day were 5.94 +/- 0.47%/day and 104 +/- 9 mg.kg body wt-1.day-1, respectively. The 6 and 16% increases (P < 0.05) in FSR and ASR after exercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), an increased total protein content throughout recovery (P < 0.05), and a negative free water clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variables were unchanged from their baselines on the time control study day. Increased albumin content and reduced free water clearance contribute to a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for the entire increase in albumin content at 6 h of recovery from exercise. However, we estimate that if the increased activity was maintained for the next 18 h, it could account for the expected increase in albumin content at 24 h of recovery.

Adult↗
PubMed1998

Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men.

Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver and principally from two sources: FA synthesized de novo in the liver and preformed FA. We have measured the contribution from the two sources to very low density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate, stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state, and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate-enriched diet (approximately 2.5 times energy expenditure). The secretion of de novo palmitate was increased 15- and 43-fold after 1 and 4 days of hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0 micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/-0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal), 28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease the secretion while 4 days increased the secretion of all preformed FA in VLDL TG. The rate of secretion of preformed palmitate and oleate were almost identical (palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1 micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and 356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted for 80-90% of the secretion from the preformed source. Palmitate is the predominant product of acute and prolonged carbohydrate mediated lipogenesis in the human liver. The pathway of further elongation and subsequent desaturation of de novo synthesized palmitate to generate stearate and oleate is inducible but, quantitatively, of minor significance in hepatic lipogenesis.

Dietary Carbohydrates↗
PubMed1997

Transient cranial hemorrhage does not cause depressed contractility in cardiac neural crest-ablated chick embryos.

Ablation of cardiac neural crest results in cardiovascular malformations. Depressed ventricular contractility has been noted in cardiac neural crest-ablated embryos several hours before the time when neural crest cells would have arrived in the cardiac outflow tract and several days before the appearance of any malformations. The reason for this depressed heart function is not known. Recently, transient cranial hemorrhages were found in chick embryos during the third day of incubation, several hours before depressed ventricular contractility can be measured. We sought to determine whether depressed ventricular contractility could be associated with these transient hemorrhages. We were also interested in defining some of the factors that influence the incidence and severity of hemorrhaging. Three groups of embryos were used: cardiac neural crest-ablated, sham-operated, and unopened controls. All groups were found to experience transient hemorrhage from a common origin in the forebrain. However, the incidence and degree of hemorrhage were higher and more severe in embryos with cardiac neural crest ablation than in the other two groups. The cardiac ejection and shortening fractions were measured at stage 18 in embryos with and without hemorrhaging, and it was found that a decrease in these parameters was associated solely with ablation of cardiac neural crest and not with hemorrhage. By altering the incubation conditions, we determined that conditions that increase the oxygen in the air space are associated with increased severity and occurrence of hemorrhage and decreased viability in the first 3 days of incubation. Our results indicate that transient cranial hemorrhages does not cause depressed contractility in cardiac neural crest-ablated embryos, and increased severity of hemorrhaging is most likely due to an increase in oxygen availability.

Acute Disease↗
PubMed1997

Measurement of very low stable isotope enrichments by gas chromatography/mass spectrometry: application to measurement of muscle protein synthesis.

Measurement of muscle protein synthesis using stable isotopically labeled tracers usually requires isotope ratio mass spectrometry (IRMS) because of the need to measure very low enrichments of stable isotopically labeled tracers (tracer to tracee ratio [TTR], 0.005% to 0.10%). This approach is laborious, requiring purification of the metabolite of interest and combustion to a gas for IRMS analysis, and is best suited for use with 13C tracers. We have developed an approach whereby low enrichments can be conveniently measured by a conventional gas chromatography/mass spectrometry (GC/MS) instrument. The approach includes three critical elements: (1) use of a highly substituted tracer containing three or more labeled atoms, to measure enrichment above a very low natural abundance of highly substituted isotopomers; (2) use of a highly substituted natural abundance isotopomer as a base ion for comparison rather than the most abundant m + 0 isotopomer, to reduce the dynamic range of the isotopomer ratio measurement; and (3) a sensitive mass spectrometric analysis that measures the natural abundance of the isotopomer used as a tracer with a high signal to noise ratio (> 100:1). This approach was used to measure the rate of synthesis of muscle protein following a primed continuous infusion of L-[13C6]-phenylalanine (PHE) in eight fasted dogs and L-[2H3]-leucine in five fasted human subjects. Values for [13C6]-PHE enrichment by GC/MS rates were virtually identical to those obtained by a conventional approach using high-performance liquid chromatography (HPLC) to isolate PHE, combustion to CO2, and measurement of 13CO2 enrichment by IRMS (IRMS enrichment = 0.9988 x GC/MS enrichment, R2 = .891), resulting in identical values for muscle fractional synthesis rates ([FSRs] mean +/- SEM: 2.7 +/- 0.2 and 2.5 +/- 0.2%/d for GC/MS and IRMS, respectively). Human muscle synthesis rates measured by GC/MS analysis of [2H3]-leucine enrichment (1.90 +/- 0.17%/d) were similar to published values based on IRMS analysis using a 1- 13C-leucine tracer. We conclude that compared with the IRMS approach, the GC/MS approach offers faster throughput, has a lower sample requirement, and is suitable for a wider variety of tracers such as 2H. The principles outlined here should be applicable to the measurement of low enrichments by GC/MS in a wide variety of stable isotope tracer applications.

Adult↗
PubMed1997

Urea and protein metabolism in burned children: effect of dietary protein intake.

The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and skin protein synthesis rates to dietary protein intake (1.15 to 2.92 g/kg/d) was assessed in children with 20% to 40% total body surface area burn injury using a primed continuous infusion of 15N2-urea and L-13C6-phenylalanine. Plasma urea concentration, production, and excretion rates increased with dietary protein intake without evidence of approaching maximum plateau values. There was no consistent evidence of urea recycling in these subjects (urea production = excretion) at any level of protein intake. The rate of appearance (Ra) of phenylalanine (an index of whole-body protein breakdown) and rate of muscle protein synthesis were independent of dietary protein, whereas there was a significant increase in skin protein synthesis with higher protein intake. We conclude that there seems to be little benefit of high protein intake on whole-body protein breakdown and muscle protein synthesis rates in these burn patients, although high-protein diets may enhance wound healing.

Adolescent↗
PubMed1997

Substrate utilization/insulin resistance in sepsis/trauma.

Endogenous substrate metabolism is markedly altered in critically ill patients. Glucose production is elevated not only in the post-absorptive state, but the normal suppressive effect of exogenous glucose and glucose production is greatly diminished. In the post-absorptive state, glucose clearance is generally elevated, potentially causing hypoglycaemia in extreme cases. Somewhat paradoxically, the ability of insulin to stimulate glucose uptake is diminished, so that hyperglycaemia is often evident during nutritional intake. Lipolysis, the breakdown of peripheral fat, is accelerated, meaning that free fatty acids are released into plasma at a rate far exceeding their oxidation. Some of the excess fatty acids are re-esterified in the liver, leading to accelerated hepatic triglyceride formation. A large increase in hepatic triglyceride stores can ensue if the rate of excretion of triglycerides in very low density lipoproteins is not accelerated commensurately with the increased triglyceride production. Indirect calorimetry measurements support the notion that the large increase in availability of fatty acids may lead to a greater reliance on fatty acids as energy substrates. Nonetheless, carbohydrates should be the predominant source of non-protein calories, because the accompanying insulin response effectively enhances protein synthesis. There is already ample fat available via endogenous lipolysis, and more fat given exogenously provides little further benefit.

Animals↗
PubMed1997

Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding.

The magnitude of the capacity to convert carbohydrate to fat in the human body is still controversial, as is the extent to which it takes place in the liver as opposed to the adipose tissue. We calculated whole-body net fat synthesis from indirect calorimetry and substrate balance data from five healthy men in the basal state and after 1 and 4 d on a hyperenergetic carbohydrate diet (approximately 2.5 times energy expenditure). At the same time, the secretion of fatty acids synthesized in the liver was measured to determine the extent to which fat synthesis occurs in the liver in a lipogenic state. The respiratory exchange ratio (RER) was 0.81 +/- 0.01 in the basal state and 0.99 +/- 0.025 and 1.15 +/- 0.022 on days 1 and 4, respectively. Although there was net fat oxidation in the basal state (955 +/- 139 mg.kg-1.min-1), there was net fat synthesis at the whole-body level both during early (day 1; 481 +/- 205 mg.kg-1.min-1) and late (day 4; 2243 +/- 253 mg.kg-1.min-1) carbohydrate overfeeding. Although hepatic secretion of fat synthesized de novo increased approximately 35-fold during the study (basal state, 1.0 +/- 0.3; day 1, 13.8 +/- 6.8; and day 4, 43.3 +/- 16.3 mg.kg-1.min-1) this could only account for a small portion of total fat synthesis. We conclude that the liver plays a quantitatively minor role when surplus carbohydrate energy is converted into fat in the human body. The main site for fat synthesis is likely to be the adipose tissue.

Adult↗
PubMed1997

Energy expenditure of swimmers during high volume training.

The purpose of this study was to examine the total energy expenditure (TEE) of swimmers during high volume training (17.5 +/- 1.0 km.d-1) using the doubly labeled water method. Five female swimmers (age, 19 +/- 1 yr; height, 178.3 +/- 2.2 cm; weight 65.4 +/- 1.6 kg) were administered a dose of 2H2(18)O and monitored for 5 days. Training consisted of two sessions per day, lasting a total of 5-6 h. Energy intake (EI) was calculated from dietary records. Resting energy expenditure (REE) was measured on a non-training day and averaged 7.7 +/- 0.5 MJ.d-1 (1840 +/- 130 kcal.d-1). There were no changes in body weight (day 1, 65.4 +/- 1.6; day 5, 65.2 +/ 1.5 kg) over the measurement period. TEE of the swimmers during the training period averaged 23.4 +/- 2.1 MJ.d-1 (5593 +/- 495 kcal.d-1). EI averaged 13.1 +/- 1.0 MJ.d-1 (3136 +/- 227 kcal.d-1), implying a negative energy balance of 43 +/- 2%. TEE expressed as a multiple of REE was 3.0 +/- 0.2. The results of this investigation describe the total energy demands of high volume swimming training, which may be used to address the dietary concerns of the competitive swimming athlete.

Adolescent↗
PubMed1997

Glucose kinetics in interstitial fluid can be predicted by compartmental modeling.

The purposes of this study were to define in sheep a compartmental model for glucose kinetics in the basal condition and to test the hypothesis that interstitial fluid obtained by sampling thoracic duct lymph (TDL) represents one or more peripheral compartments of the glucose model. A bolus of [6,6-(2)H]glucose was injected in nine animals, followed by frequent sampling of blood and TDL. Linear kinetic modeling has been applied to plasma data, indicating that a three-compartment model adequately describes glucose kinetics. Both catenary and mammillary models were identified, and their predictions for the tracer behavior in nonaccessible pools were evaluated. In all experiments, regardless of the model structure, predictions in the compartment most rapidly exchanging with blood (pool 2) well matched the measured tracer-to-tracee ratio in TDL. Furthermore, modeling analysis showed that 90-95% of the tracer in TDL comes from this pool. This supported the physiological identification of a peripheral pool of glucose kinetics as extracellular fluid represented by TDL measurements.

Animals↗
PubMed1997

Regulation of plasma fatty acid oxidation during low- and high-intensity exercise.

In the present study we examined the hypothesis that fatty acid oxidation is less during high-intensity exercise than during moderate-intensity exercise because of inhibition of long-chain fatty acid entry into the mitochondria. Six volunteers exercised at 40% peak oxygen consumption (VO2peak) for 60 min and at 80% VO2peak for 30 min on two different occasions. [1-13C]oleate, a long-chain fatty acid, and [1-14C]octanoate, a medium-chain fatty acid, were infused for the duration of the studies. Lipids and heparin were infused during exercise at 80% VO2peak to prevent the expected decrease in plasma free fatty acid (FFA) concentration. Plasma oleate and total FFA availability were similar in the two experiments. Oleate oxidation decreased from 2.8 +/- 0.6 (40% VO2peak) to 1.8 +/- 0.2 mumol.kg-1.min-1 (80% VO2peak, P < 0.05), whereas octanoate oxidation increased from 1.0e-05 +/- 1.0e-06 (40% VO2peak) to 1.3e-05 +/- 5.1e-06 mumol.kg-1.min-1 (80% VO2peak, P < 0.05). Furthermore, the percentage of oleate uptake oxidized decreased from 67.7 +/- 2.8% (40% VO2peak) to 51.8 +/- 4.6% (80% VO2peak, P < 0.05), whereas the percentage of octanoate oxidized was similar during exercise at 40 and 80% VO2peak (84.8 +/- 2.7 vs. 89.3 +/- 2.7%, respectively). Our data suggest that, in addition to suboptimal FFA availability, fatty acid oxidation is likely limited during high-intensity exercise because of direct inhibition of long-chain fatty acid entry into mitochondria.

Adult↗
PubMed1997

An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein.

Six normal untrained men were studied during the intravenous infusion of a balanced amino acid mixture (approximately 0.15 g.kg-1.h-1 for 3 h) at rest and after a leg resistance exercise routine to test the influence of exercise on the regulation of muscle protein kinetics by hyperaminoacidemia. Leg muscle protein kinetics and transport of selected amino acids (alanine, phenylalanine, leucine, and lysine) were isotopically determined using a model based on arteriovenous blood samples and muscle biopsy. The intravenous amino acid infusion resulted in comparable increases in arterial amino acid concentrations at rest and after exercise, whereas leg blood flow was 64 +/- 5% greater after exercise than at rest. During hyperaminoacidemia, the increases in amino acid transport above basal were 30-100% greater after exercise than at rest. Increases in muscle protein synthesis were also greater after exercise than at rest (291 +/- 42% vs. 141 +/- 45%). Muscle protein breakdown was not significantly affected by hyperminoacidemia either at rest or after exercise. We conclude that the stimulatory effect of exogenous amino acids on muscle protein synthesis is enhanced by prior exercise, perhaps in part because of enhanced blood flow. Our results imply that protein intake immediately after exercise may be more anabolic than when ingested at some later time.

Adult↗
PubMed1997

Mixed muscle protein synthesis and breakdown after resistance exercise in humans.

Mixed muscle protein fractional synthesis rate (FSR) and fractional breakdown rate (FBR) were examined after an isolated bout of either concentric or eccentric resistance exercise. Subjects were eight untrained volunteers (4 males, 4 females). Mixed muscle protein FSR and FBR were determined using primed constant infusions of [2H5]phenylalanine and 15N-phenylalanine, respectively. Subjects were studied in the fasted state on four occasions: at rest and 3, 24, and 48 h after a resistance exercise bout. Exercise was eight sets of eight concentric or eccentric repetitions at 80% of each subject's concentric 1 repetition maximum. There was no significant difference between contraction types for either FSR, FBR, or net balance (FSR minus FBR). Exercise resulted in significant increases above rest in muscle FSR at all times: 3 h = 112%, 24 h = 65%, 48 h = 34% (P < 0.01). Muscle FBR was also increased by exercise at 3 h (31%; P < 0.05) and 24 h (18%; P < 0.05) postexercise but returned to resting levels by 48 h. Muscle net balance was significantly increased after exercise at all time points [(in %/h) rest = -0.0573 +/- 0.003 (SE), 3 h = -0.0298 +/- 0.003, 24 h = -0.0413 +/- 0.004, and 48 h = -0.0440 +/- 0.005], and was significantly different from zero at all time points (P < 0.05). There was also a significant correlation between FSR and FBR (r = 0.88, P < 0.001). We conclude that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.

Adult↗
PubMed1997

Regulation of glucose production during exercise at 80% of VO2peak in untrained humans.

To determine whether alterations in insulin and/or glucagon secretion play an important role in stimulating glucose production (Ra) during intense but submaximal exercise, we studied six untrained subjects during 30 min of cycling at 80% of peak oxygen uptake on two occasions: once under control conditions and once when alterations in insulin and glucagon secretion were prevented with the use of the pancreatic islet clamp technique. In the latter experiments, glucose was infused during exercise to match glycemia with control levels. Glucose kinetics were measured in both trials using a primed, continuous infusion of [6,6-2H]glucose. In the control trial, glucose Ra rose from 11.9 +/- 0.8 mumol.min-1.kg-1 at rest to 42.5 +/- 4.3 mumol.min-1.kg-1 by the end of exercise. A similar increment was observed in the islet clamp experiments, with endogenous Ra peaking at 37.2 +/- 7.9 mumol.min-1.kg-1. This was true even through glucagon concentration did not change from basal and insulin concentration actually rose (the latter apparently due to a decrease in insulin clearance during intense exercise). Thus neither decrements in insulin or increments in glucagon are apparently required to stimulate glucose Ra under the present conditions. Because epinephrine levels rose only slightly, it appears that either neurally released norepinephrine or some other, as yet unidentified, factor is responsible for stimulating glucose Ra during intense but submaximal exercise.

Adult↗
PubMed1997

Resistance exercise maintains skeletal muscle protein synthesis during bed rest.

Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength. We therefore hypothesized that scheduled resistance training throughout bed rest would ameliorate the decrease in MPS. Two groups of healthy volunteers were studied during 14 days of simulated microgravity. One group adhered to strict bed rest (BR; n = 5), whereas a second group engaged in leg resistance exercise every other day throughout bed rest (BREx; n = 6). MPS was determined directly by the incorporation of infused L-[ring-13C6] phenylalanine into vastus lateralis protein. After 14 days of bed rest, MPS in the BREx group did not change and was significantly greater than in the BR group. Thus moderate-resistance exercise can counteract the decrease in MPS during bed rest.

Adult↗
PubMed1996

Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria.

We tested the hypothesis that glucose plus insulin determine the rate of fat oxidation in humans by controlling the rate of fatty acid entrance into the mitochondria. We gave constant infusions of [1-13C]oleate, a long-chain fatty acid, and [1-14C]octanoate, a medium-chain fatty acid, for 3 h in seven volunteers (basal). Immediately after the basal period, a hyperinsulinemic (insulin infusion = 120 mU x m(-2) min(-1)), hyperglycemic (plasma glucose = 140 mg/dl) clamp was started and continued for 5 h. During the last 3 h of the clamp, the infusions of [1-13C]oleate and [1-14C]octanoate were repeated. Intracellular acylcarnitine concentrations were measured in muscle biopsies obtained before and after the clamp. Plasma oleate enrichment and FFA concentration were kept constant by means of variable infusions of lipids and heparin. Oleate, but not octanoate, requires carnitine binding to gain access to the mitochondrial matrix; hence, if glucose and/or insulin limit long-chain fatty acid entrance into the mitochondria, then, during the clamp, long-chain acylcarnitine formation should be decreased, causing a decrease in oleate, but not octanoate, oxidation. Oleate oxidation decreased from the basal value of 0.7+/-0.1 to 0.4+/-0.1 micromol x kg(-1) x min(-1) (P < 0.05). In contrast, octanoate oxidation remained unchanged. Long-chain acylcarnitine concentration decreased from 855+/-271 in the basal state to 376+/-83 nmol/gram dry weight during the clamp (P < 0.05). We conclude that glucose and/or insulin determine fatty acid oxidation by controlling the rate of long-chain fatty acid entrance into the mitochondria.

Adult↗
PubMed1996

Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man.

Triglycerides (TG) are synthesized in the liver principally from two sources of fatty acids (FA): FA synthesized de novo in the liver and preformed FA. We have measured the rate of secretion of de novo synthesized FA and total secretion of FA bound to VLDL-TG in healthy men (n = 5) in the basal state, and after 1 (day 1) and 4 d (day 4) of a hypercaloric carbohydrate diet (approximately 2.5 times energy expenditure) that generated a moderate endogenous hyperinsulinemia (plasma insulin approximately 60 microU/ml). Prolonged carbohydrate hyperalimentation/hyperinsulinemia increased plasma VLDL-TG approximately 10-fold in part due to a 3.4-fold increase in total VLDL-TG secretion rate (basal state = 72+/-23, day 4 = 242+/-78 micromol TG/kg/d). Although the secretion of de novo synthesized FA increased throughout the study (basal state = 1.1+/-0.4, day 1 = 15.9+/-7.9, day 4 = 50.0+/-18.8 micromol TG/ kg/d), the 2.7-fold increase in secretion rate of preformed FA (basal state = 70+/-23, day 4 = 191+/-57 micromol TG/kg/d) quantitatively contributed the most to total VLDL-TG secretion rate. Decreased catabolism of VLDL-TG also contributed to the hypertriglyceridemia as reflected by an approximately fourfold decrease in both fractional turnover rate (basal state = 9.2+/-3.8, day 1 = 2.1+/-0.2, day 4 = 2.1+/-0.3 pools/d) and rate of clearance (basal state = 0.35+/-0.08, day 1 = 0.11+/-0.01, day 4 = 0.09+/-0.01 liter/kg/d) of VLDL-TG. Thus, the primary difference between 1 and 4 d of hyperinsulinemia in conjunction with carbohydrate hyperalimentation is the increase in hepatic secretion of preformed FA into VLDL-TG.

Adult↗