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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 199 records · Page 11Linked to original sources
PubMed1991

Propranolol diminishes extremity blood flow in burned patients.

Beta adrenergic blockade diminishes the catecholamine-mediated elevations in heart rate and myocardial contractility that characterize postburn hypermetabolism. To examine how these alterations in cardiac performance affect peripheral perfusion, indirect calorimetry and leg blood flow were measured before and then after a 2-hour intravenous propranolol infusion. Five severely burned patients (55% + 7% total burn surface area), given propranolol at 8 micrograms/kg/minute, had a significant reduction in cardiac index and heart rate with an increased leg vascular resistance resulting in a decrease in extremity perfusion. Four healthy volunteers were given propranolol at 5 micrograms/kg/minute, resulting in a comparable decrease in heart rate, yet there was no change in leg vascular resistance or extremity perfusion. In both patient groups, propranolol decreased the plasma lactate concentration. This suggests that in hypermetabolic patients, beta adrenergic blockade reduces peripheral perfusion and that peripheral perfusion is not a principal determinate of plasma lactate levels. Rather adrenergic blockade appears to decrease lactate concentration as a consequence of the inhibition of lipolysis.

Adult↗
PubMed1991

Lipolytic response to metabolic stress in critically ill patients.

OBJECTIVE: To measure whole-body lipolysis and fatty acid re-esterification in critically ill patients. DESIGN: The rates of appearance of glycerol and palmitic acid in blood plasma were measured by infusing stable isotope tracers [2H5]glycerol and [1-13C]palmitic acid, respectively. Energy expenditure was measured by indirect calorimetry. SETTING: Medical ICU of The University of Texas Medical Branch Hospital, a university-based referral center. PATIENTS: Five uninjured critically ill patients. Four patients were hospitalized because of respiratory insufficiency and one because of myocardial infarction. Three patients died during their hospitalization. INTERVENTIONS: Metabolic studies were performed in each patient after an overnight (12-hr) fast. MEASUREMENTS AND MAIN RESULTS: Mean +/- SE glycerol and fatty acid rates of appearance were 4.5 +/- 1.0 and 11.5 +/- 0.8 mumol/kg.min, respectively. The ratio of fatty acid to glycerol rate of appearance was 2.9 +/- 0.5. Resting energy expenditure was 132 +/- 6% of predicted. CONCLUSIONS: An accelerated rate of lipolysis is part of the metabolic response to severe stress, regardless of its etiology. Because the rate of fatty acid release far exceeded energy requirements, fatty acids that were not oxidized as fuel were re-esterified to triglyceride, presumably in the liver.

Acute Disease↗
PubMed1991

Effect of short-term fasting on the lipolytic response to theophylline.

We investigated the hypothesis that the increase in lipolysis that occurs in short-term (86-h) fasting is due to a decreased inhibitory influence of adenosine. In normal volunteers who fasted for 14 and 86 h, the response to adenosine receptor blockade was assessed by the infusion of theophylline at a rate sufficient to produce plasma concentrations (30 microM) that blocked adenosine receptors but that were well below the threshold for inhibition of phosphodiesterase. Lipolysis was assessed by determining the rate of appearance of glycerol using D-5-glycerol infusion. Fatty acid flux was also determined by means of [1-13C]palmitate infusion, and total fatty acid oxidation was determined by indirect calorimetry. There was a mild stimulatory effect of theophylline on lipolysis at 14 h. After the subjects fasted for 86 h, theophylline infusion caused a much greater increase in both lipolysis and fatty acid oxidation. These results suggest that the inhibitory effect of adenosine on lipolysis is increased during short-term fasting.

Adult↗
PubMed1991

Increased dependence on blood glucose after acclimatization to 4,300 m.

To evaluate the hypothesis that altitude exposure and acclimatization result in increased dependency on blood glucose as a fuel, seven healthy males (23 +/- 2 yr, 72.2 +/- 1.6 kg, mean +/- SE) on a controlled diet were studied in the postabsorptive condition at sea level (SL), on acute altitude exposure to 4,300 m (AA), and after 3 wk of chronic altitude exposure to 4,300 m (CA). Subjects received a primed continuous infusion of [6,6-2D]glucose and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the SL maximal O2 consumption (VO2 max; 65 +/- 2% of altitude VO2 max). At SL, resting arterial glucose concentration was 82.4 +/- 3.2 mg/dl and rose significantly to 91.2 +/- 3.2 mg/dl during exercise. Resting glucose appearance rate (Ra) was 1.79 +/- 0.02 mg.kg-1.min-1; this increased significantly during exercise at SL to 3.71 +/- 0.08 mg.kg-1.min-1. On AA, resting arterial glucose concentration (85.8 +/- 4.1 mg/dl) was not different from sea level, but Ra (2.11 +/- 0.14 mg.kg-1.min-1) rose significantly. During exercise on AA, glucose concentration rose to levels seen at SL (91.4 +/- 3.0 mg/dl), but Ra increased more than at SL (to 4.85 +/- 0.15 mg.kg-1.min-1; P less than 0.05). Resting arterial glucose was significantly depressed with CA (70.8 +/- 3.8 mg/dl), but resting Ra increased to 3.59 +/- 0.08 mg.kg-1.min-1, significantly exceeding SL and AA values.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed1991

Decreased reliance on lactate during exercise after acclimatization to 4,300 m.

We hypothesized that the increased exercise arterial lactate concentration on arrival at high altitude and the subsequent decrease with acclimatization were caused by changes in blood lactate flux. Seven healthy men [age 23 +/- 2 (SE) yr, wt 72.2 +/- 1.6 kg] on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-2D]glucose (Brooks et al. J. Appl. Physiol. 70:919-927, 1991) and [3-13C]lactate and rested for a minimum of 90 min followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 consumption (VO2peak; 65 +/- 2% of both acute altitude and acclimatization). During rest at sea level, lactate appearance rate (Ra) was 0.52 +/- 0.03 mg.kg-1.min-1; this increased sixfold during exercise to 3.24 +/- 0.19 mg.kg-1.min-1. On acute exposure, resting lactate Ra rose from sea level values to 2.2 +/- 0.2 mg.kg-1.min-1. During exercise on acute exposure, lactate Ra rose to 18.6 +/- 2.9 mg.kg-1.min-1. Resting lactate Ra after acclimatization (1.77 +/- 0.25 mg.kg-1.min-1) was intermediate between sea level and acute exposure values. During exercise after acclimatization, lactate Ra (9.2 +/- 0.7 mg.kg-1.min-1) rose from resting values but was intermediate between sea level and acute exposure values. The increased exercise arterial lactate concentration response on arrival at high altitude and subsequent decrease with acclimatization are due to changes in blood lactate appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1991

Glucose and lactate kinetics in the neonate.

To evaluate the ontogeny of neonatal glucose homeostasis, glucose production and lactate production have been measured in nine prematurely born appropriate for gestational age neonates [birth weight 1985 +/- 100 g, (SEM) gestational age 33.6 +/- 0.7 weeks] and five full term appropriate for gestational age neonates [birth weight 3254 +/- 111 g, gestational age 40.8 +/- 0.4 wks] and compared to six non pregnant, nondiabetic adults [weight of 57.7 +/- 2.2 kg, age 32 +/- 2 years]. Ra glucose (preterm) averaged 27.7 +/- 2.8 mumol.kg-1 min-1 (5.0 +/- 0.5 mg.kg-1 min-1) and Ra glucose (term) averaged 28.9 +/- 3.9 mumol.kg-1 min-1 (5.2 +/- 0.7 mg.kg-1 min-1); both were higher than the Ra glucose of the adult controls (16.1 +/- 2.8 mumol.kg-1 min-1 (2.9 +/- 0.5 mg.kg-1 min-1) (P less than 0.05 vs preterm and P less than 0.05 vs. term). Ra lactate (preterm) averaged 100 +/- 11.9 mumol.kg-1 min-1 (9.1 +/- 1.1 mg.kg-1 min-1) and Ra lactate (term) average 77.2 +/- 13.0 mumol.kg-1 min-1 (7.1 +/- 1.2 mg.kg-1 min-1); both were higher than the Ra lactate of the adult controls 35.9 +/- 6.5 mumol.kg-1 min-1 (3.3 +/- 0.6 mg.kg-1 min-1) (P less than 0.01 vs preterm and P less than 0.05 vs. term). The potential for gluconeogenesis from lactate was estimated by determining the ratio of [Ra Lactate/Ra Glucose]. The [Ra Lactate/Ra Glucose] (preterm) (187 +/- 12 (x10(-2)) was similar to that of the [Ra Lactate/Ra Glucose] (term) (136 +/- 16) (x10(-2)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion.

In this study we have assessed the hypothesis that there is a postreceptor defect in glucose metabolism that makes the severely burned patient unable to oxidize glucose efficiently as an energy source. The intracellular pyruvate pool was labeled by the infusion of 3-13C-lactate, and expired CO2 production and isotopic enrichment of both pyruvate and CO2 were determined to calculate the rate of pyruvate production and oxidation. 6,6-d2-Glucose and 15N-alanine were infused simultaneously to relate pyruvate kinetics and oxidation to glucose and alanine kinetics. Five normal volunteers and 10 severely burned patients (mean of 80% +/- 5% body surface burned) were studied in the basal state and during continuous (unlabeled) glucose infusion. Also, the effect of dichloroacetate, which normally stimulates pyruvate dehydrogenase activity, was assessed in both volunteers and patients. The burned patients had many of the classic metabolic responses to severe injury, including significant increases in resting energy expenditure, glucose production, and alanine release from protein breakdown. However, rather than being inhibited, the rate of pyruvate oxidation was increased approximately 300% in burned patients. Although the patients had an elevated mean concentration of lactate, stemming from increased lactate production, no deficit in pyruvate dehydrogenase activity was evident. Rather, the high rate of lactate production was apparently a consequence of the high rate of glycolysis. On the other hand, the direct pathway for synthesis of glycogen from infused glucose appeared to be impaired in burned patients. In both volunteers and patients, dichloroacetate stimulated the percent of pyruvate directed to oxidation, thereby reducing the conversion of pyruvate to other fates, including lactate. However, because there was no deficit in pyruvate dehydrogenase activity in the patients compared with normal volunteers before dichloroacetate treatment, no unique effect of dichloroacetate on glucose or protein kinetics was observed in burned patients. From these results we conclude that if there is a postreceptor defect in glucose metabolism in burned patients, it involves the pathway of direct glycogen synthesis and not the pathway of oxidation.

Absorption↗
PubMed1990

Effect of low-dose bradykinin on glucose metabolism and nitrogen balance in surgical patients.

Acute effects of a low-dose bradykinin infusion (30 ng/kg per min) on carbohydrate metabolism were studied in five patients after major burn injury. Peripheral glucose uptake was not affected but glucose oxidation and alanine flux were increased by 15% and 10%, respectively. These findings are compatible with an increase in glycolytic flux by an action of bradykinin. Nineteen patients who had undergone major gastro-intestinal surgery were studied in a randomised trial of chronic (6 day) bradykinin administration. Patients in the bradykinin group had a significantly improved rate of nitrogen retention (cumulative N balance, -0.014 [SE 0.064] vs -0.175 [0.048] g N/kg) in controls and significantly better nutritional indices. Manipulation of metabolism in surgical patients by bradykinin may have beneficial effects on nitrogen and protein dynamics, possibly mediated by improved aerobic and anaerobic glycolysis.

Adolescent↗
PubMed1990

Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: implications for tracer studies of substrate oxidation.

In this study we determined the rate of conversion of carbon-labeled acetate to carbon dioxide in normal human volunteers and in anesthetized dogs. In human subjects (n = 4), [1-13C]acetate was infused on one occasion, and [2-13C]acetate was infused in the repeat study in the same subjects. In postabsorptive volunteers (n = 6), 81.2 +/- 6.5% (mean +/- SEM) and 53.1 +/- 7.4% of infused 13C was recovered as 13CO2 when [1-13C]- or [2-13C]acetate, respectively, were infused. In one subject studied during exogenous glucose infusion at 3.5 mg.kg-1.min-1, recovery of 13CO2 was 72.7% and 38.5% from [1-13C]- and [2-13C]acetate, respectively. In dogs, [1-14C]- and [2-13C]acetate were infused simultaneously. Recovery of 14CO2 was 75.9 +/- 2.5% of infused isotope whereas recovery of 13CO2 was 40.8 +/- 1.9%. We concluded that the position of the label in acetyl coenzyme A (CoA) determines the extent to which the process of oxidation of labeled acetyl CoA is reflected in labeled carbon dioxide excretion.

Acetates↗
PubMed1990

Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis.

To determine whether increasing dietary protein could exert a beneficial effect on bed-rest-related protein catabolism, two groups of normal subjects were subjected to 7 d of bed rest while taking isocaloric diets containing either 0.6 or 1.0 g protein.kg body wt-1.d-1. Whole-body-leucine turnover, leucine oxidation, and nonoxidative leucine disappearance were measured by use of a constant infusion of 1-13C-leucine. Before bed rest, the higher-protein diet resulted in a 14% decrease in whole-body-leucine turnover and a 28% decrease in leucine oxidation, but net nonoxidative leucine disappearance was not different on the two diets. A 24% decrease in nonoxidative leucine disappearance was seen in subjects assigned to the lower-protein diet, who had been on bed rest, but on the higher-protein diet, leucine kinetics were unchanged by bed rest. Bed rest does not cause an increase in whole-body-protein breakdown, but decreased whole-body-protein synthesis is demonstrable when dietary protein is low. This decrease is prevented by a higher dietary amount of protein.

Adult↗
PubMed1990

Importance of blood glucose concentration in regulating lipolysis during fasting in humans.

The importance of the decline in blood glucose concentration on lipolysis and the lipolytic effect of epinephrine was evaluated during short-term fasting. Lipolytic rates were determined by infusing [2H5]glycerol and [1-13C]palmitic acid. Five volunteers were studied after 12 h of fasting before and during epinephrine infusion and after 84 h of fasting, before and during glucose infusion when plasma glucose was restored to postabsorptive values, and during glucose plus epinephrine infusion. In another protocol, five volunteers were given glucose intravenously throughout fasting to maintain plasma glucose at postabsorptive levels and isotopic studies were performed after 12 and 84 h of fasting before and during epinephrine infusion. Glucose infusion after 84 h of fasting restored glucose and insulin concentrations and lipolytic rates toward 12-h fasting values. When euglycemia was maintained throughout fasting, plasma insulin still declined (P less than 0.05) and lipolytic rates still increased (P less than 0.05). Despite similar glucose concentrations, the lipolytic response to epinephrine infusion was greater after 84 h than after 12 h of fasting in both protocols (P less than 0.05). These studies demonstrate that the decline in plasma glucose contributes to, but is not required for, the increase in lipolysis during fasting. The increase in epinephrine-stimulated lipolysis that occurs during fasting is not dependent on a decrease in plasma glucose concentration.

Adult↗
PubMed1990

The relationship between gluconeogenic substrate supply and glucose production in humans.

The relationship between gluconeogenic precursor supply and glucose production has been investigated in 14-h and 86-h fasted humans. In protocols 1 and 2 [6,6-2H]glucose and [15N2]urea were infused to measure glucose and urea production rates (Ra) in response to infusions of glycerol and alanine. In protocol 3 first [15N]alanine, [3-13C]lactate, and [6,6-2H]glucose were infused before and during administration of dichloroacetate (DCA) to determine the response of glucose Ra to decreased fluxes of pyruvate, alanine, and lactate, then alanine was infused with DCA and glucose Ra measured. After a 14-h fast, neither alanine nor glycerol increased glucose Ra. Basal glucose Ra decreased by one-third after 86 h of fasting, yet glycerol and alanine infusions had no effect on glucose Ra. Glycerol always reduced urea Ra (P less than 0.05), suggesting that glycerol competitively inhibited gluconeogenesis from amino acids. DCA decreased the fluxes of pyruvate, alanine (P less than 0.01), and glucose Ra (P less than 0.01), which was prevented by alanine infusion. These findings suggest that 1) the reduction in glucose Ra after an 86-h fast is not because of a shortage of gluconeogenic substrate; 2) nonetheless, the importance of precursor supply to maintain basal glucose Ra is confirmed by the response to DCA; 3) an excess of one gluconeogenic substrate inhibits gluconeogenesis from others.

Adult↗
PubMed1990

Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise.

We have investigated the role of triglyceride-fatty acid cycling in amplifying control of the net flux of fatty acids in response to exercise and in recovery from exercise. Five normal volunteers were infused with [1-13C]palmitate and D-5-glycerol throughout rest, 4 h of treadmill exercise at 40% maximum O2 consumption, and 2 h of recovery. Total fat oxidation was quantified by indirect calorimetry. Lipolysis (rate of appearance of glycerol) increased from 2.1 +/- 0.3 to 6.0 +/- 1.2 mumol.kg-1.min-1 after 30 min of exercise and progressively increased thereafter to a value of 10.5 +/- 0.8 mumol.kg-1.min-1 after 4 h. Lipolysis decreased rapidly during the first 20 min of recovery, but it was still significantly elevated after 2 h of recovery. The rate of appearance of free fatty acids followed the same pattern of response. Seventy percent of released fatty acids were reesterified at rest, and this value decreased to 25% within the first 30 min of exercise. Reesterification remained less than 35% of lipolysis until the start of recovery, at which time the value rose to 90%. In exercise, more than one-half the increase in fat oxidation could be attributed to the reduction in the percent reesterification. Most of the change in percent reesterification during exercise and recovery was caused by changes in extracellular cycling of fatty acids released into plasma. We conclude that triglyceride-fatty acid cycling plays an important role in enabling a rapid response of fatty acid metabolism to major changes in energy metabolism.

Adult↗
PubMed1990

Whole body and plasma protein synthesis in exercise and recovery in human subjects.

The effect of 4 h of exercise at 40% of maximal oxygen consumption (VO2 max) on protein metabolism was assessed in normal volunteers maintained on a diet containing 42 kcal.kg-1.day-1 and either 0.9 or 2.5 g protein.kg-1.day-1. Primed constant infusions of [1,2-13C]-leucine and [15N]glycine enabled the quantitation of whole body protein turnover and also the fractional synthetic rates (FSR) of albumin, fibrinogen, and fibronectin. In subjects who did not exercise, the fractional synthetic rates (%/day) on normal and high-protein intakes, respectively, were as follows: albumin, 10 +/- 1 and 9 +/- 1; fibrinogen, 21 +/- 3 and 18 +/- 1; and fibronectin, 31 +/- 3 and 34 +/- 3. Neither exercise nor recovery had an effect of whole body protein turnover or on albumin FSR, but the FSR of fibronectin was significantly elevated at the end of exercise, and fibrinogen was significantly elevated in recovery. Dietary protein intake had no major effect on the response to exercise. Thus, in response to exercise, there is a stimulation of the synthesis of some acute phase proteins, which may be a mechanism whereby nitrogen resulting from muscle protein breakdown is spared.

Amino Acids↗
PubMed1990

Bradykinin attenuates glucagon-induced leucine oxidation in humans.

Trauma and injury are associated with accelerated protein loss. Counterregulatory hormones are possible mediators of this response. In the present study, the effect of glucagon and glucagon plus bradykinin on leucine and urea kinetics was examined in nine normal volunteers during somatostatin infusion and basal insulin replacement. Bradykinin was given because of its prostaglandin-stimulating qualities and the potential anabolic action of prostaglandins. Physiological hyperglucagonemia elicited a small but significant reduction of total leucine flux and rate of urea synthesis. Simultaneously, leucine oxidation increased by 70%. The simultaneous infusion of bradykinin did not alter glucagon-related changes in urea or leucine kinetics. Bradykinin, however, significantly attenuated the stimulation of leucine oxidation by glucagon. These results suggest that glucagon and tissue factors are involved in controlling leucine metabolism in humans.

Adult↗
PubMed1990

Effect of exercise and recovery on muscle protein synthesis in human subjects.

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.

Adult↗
PubMed1990

Total energy expenditure in burned children using the doubly labeled water technique.

Total energy expenditure (TEE) was measured in 15 burned children with the doubly labeled water technique. Application of the technique in burned children required evaluation of potential errors resulting from nutritional intake altering background enrichments during studies and from the high rate of water turnover relative to CO2 production. Five studies were discarded because of these potential problems. TEE was 1.33 +/- 0.27 times predicted basal energy expenditure (BEE), and in studies where resting energy expenditure (REE) was simultaneously measured, TEE was 1.18 +/- 0.17 times REE, which in turn was 1.16 +/- 0.10 times predicted BEE. TEE was significantly correlated with measured REE (r2 = 0.92) but not with predicted BEE. These studies substantiate the advantage of measuring REE to predict TEE in severely burned patients as opposed to relying on standardized equations. Therefore we recommend that optimal nutritional support will be achieved in convalescent burned children by multiplying REE by an activity factor of 1.2.

Adolescent↗