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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 325 records · Page 18Linked to original sources
PubMed1981

Investigation of kinetics of integrated metabolic response to adrenergic blockade in conscious dogs.

We have used multiple isotope infusions to study the integrated response of glucose, fat, and protein metabolism to combined alpha + beta-adrenergic blockade in conscious, unstressed, fasting (15 h) dogs. The response to the blocking agents was evaluated both with and without control of the glucoregulatory hormones. The hormones were controlled at the basal level by infusions of somatostatin and metyrapone to block their secretion, and by the infusion of insulin, glucagon, growth hormone, and cortisol at physiological rates. We found that adrenergic blockade markedly inhibited lipolysis, as reflected by falls in glycerol and plasma FFA appearance. The decrease in fat mobilization after blockade resulted in a proportionate shift from fat as an energy substrate toward carbohydrate. Glucose production and oxidation were both enhanced after blockade. The source of the increased glucose production was presumably hepatic glycogen because urea production was presumably hepatic glycogen because urea production was unaffected and glycerol uptake was decreased. These results are consistent with the interpretation that basal adrenergic activity plays an important role in the mobilization of fat in fasting dogs. A secondary consequence of that action is apparently a diminution of glucose production and oxidation, although the mechanism responsible for the latter response is not clear.

Animals↗
PubMed1981

Effects of adrenergic blockade on glucose kinetics in septic and burned guinea pigs.

We have used the primed-constant infusion of [6-3H]glucose to study the effects of phentolamine, an alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, on glucose production and clearance in gastrostomy-fed control, septic (repeated sub-Q Escherichia coli injections), and burned (25-30% BSA) guinea pigs. Hypermetabolism and elevated glucoregulatory hormones were evident in both traumatized models, whereas their glucose kinetic response was different. Basal glucose production and clearance were elevated in the burned group and were depressed in the septic group when compared to control values. Propranolol caused a further increase in glucose production and clearance in the burned group, whereas it depressed glucose production and clearance to an even greater extent in the septic group. Phentolamine also produced an increase in glucose production and clearance in the burned group. In the septic group, phentolamine had no significant effect on glucose production, but clearance was significantly elevated. Thus, although alpha- or beta-adrenergic blockade normalized metabolic rate in both groups with respect to control animals, glucose kinetics remained different despite similar changes in counterregulatory hormones.

Animals↗
PubMed1981

Review: acute versus chronic response to burn injury.

The acute response to burn injury is referred to as the ebb, or shock, phase. It is characterized as a hypodynamic state, with both cardiac output and metabolic rate being depressed. Hyperglycemia is evident, owing both to an increased rate of production of glucose and a peripheral "insulin resistance." Lactate production is markedly elevated, whereas the FFA response is variable. Clinically, the predominant concern is repletion of the plasma volume that was lost as a consequence of increased capillary permeability. If adequate fluid resuscitation is administered, recovery from burn shock can usually be accomplished. The chronic response to burn injury, or flow phase, may last for many weeks. It is a hyperdynamic state, with both cardiac output and metabolic rate being elevated. Without appropriate nutritional therapy, severe protein wasting can occur as a consequence of an accelerated rate of protein catabolism. The increase in protein catabolism is associated with an increase in the rate of glucose production. There appear to be changes in fat metabolism as well, but more quantitative studies are needed in this area. In general, improved emergency room treatment has greatly improved survival from burn shock, and the focus of much of the study of the response to burn injury has consequently shifted to the flow phase. In that regard, many important questions still remain unanswered. The most pressing problem to those interested in metabolism and nutrition is probably the identification of the signal for the metabolic response evident in the flow phase.

Adolescent↗
PubMed1981

Techniques for investigating substrate metabolism in patients.

Studies of dynamic aspects of substrate metabolism in patients can be made with a variety of techniques. Methods include indirect calorimetry, substrate load tests, measurement of arteriovenous differences with use of the Fick principle, and isotope infusions. Recent developments in stable isotope methodology have made available safe techniques for accurate measurement of the turnover of plasma substrates in patients. The use of deuterated, 13C, and 15N isotopes enables the turnover of several substrates to be measured at the same time. It is hoped that the primed constant infusion of stable isotopes combined with indirect calorimetry will lead to a greater understanding of metabolism in ill patients.

Calorimetry, Indirect↗
PubMed1980

Measurement of plasma free fatty acid turnover and oxidation using [1-13C]palmitic acid.

The measurement of plasma free fatty acid turnover and oxidation by means of the isotopic dilution technique using a radiolabeled free fatty acid has proven useful for the in vivo study of fat metabolism in animals. However, because of the ethical considerations regarding the administration of radioisotopes to humans, there is a lack of adequate information regarding the in vivo regulation of free fatty turnover and oxidation in humans, particularly children. Consequently, we have developed a technique using the stable, nonradioactive [1-13C]palmitic acid molecule as free fatty acid tracer to measure plasma free fatty acid metabolism in vivo. We have analysed the isotopic enrichment of plasma palmitate by selected ion monitoring on a gas chromatograph mass spectrometer and we have used an isotope ratio mass spectrometer to determine the much lower isotopic enrichment of the expired CO2. We have found this technique to be safe to administer, to a high degree of analytical reproducibility, and to yield values in dogs comparable with those obtained using [1-14C]palmitic acid as the tracer.

Animals↗
PubMed1980

Investigation of factors determining the optimal glucose infusion rate in total parenteral nutrition.

We have used the primed constant infusion of U-13C-glucose to study glucose metabolism during conventional total parenteral nutrition (TPN) in five postoperative surgical patients. Glucose production from nonrecycled carbon sources was suppressed to 17% of the basal level at the lowest rate of glucose infusion tested (4 mg/kg x min). Subsequent increases in glucose infusion rate had minimal effect in further suppressing glucose production. Additional nitrogen-sparing effects of glucose when glucose is infused at rates in excess of 4 mg/kg x min must therefore be derived from oxidation of the infused glucose. An increase in the infusion rate from 4 mg/kg x min to 7 mg/kg x min was associated with an increased rate of glucose oxidation, but a further increase in glucose infusion rate (9 mg/kg x min) was without significant effect on glucose oxidation. As the rate of TPN administration (glucose and amino acids) increased, both metabolic rate and RQ rose significantly. Our calculations indicate that the high RQ's observed during the highest glucose infusion rate (X = 1.13) could be attributed to the synthesis of fat from infused glucose, and that about 30% of the increase in VO2 above the basal level could also be attributed to fat synthesis. The progressive increase in the ability to clear glucose from the blood that occurred as TPN progressed was not due to an increase in the rate of oxidation of glucose; we found no correlation between glucose clearance and glucose oxidation.

Adult↗
PubMed1980

Effect of food intake on hypermetabolic response to burn injury in guinea pigs.

We have studied the effect of caloric intake on metabolic rate in normal and burned (20-25% body surface area, BSA) guinea pigs. Food intake was standardized by means of infusing a liquid diet (48 kcal/day) through chronic gastrostomy tubes continuously for 16 hours per day. We found that feeding control animals a diet insufficient to meet their daily caloric requirements nevertheless resulted in a significantly higher basal oxygen consumption (VO2) 8 hours after food than during fasting. The incremental increase in basal VO2 induced by feeding burned animals (20-25% BSA) was even greater than in controls. Thus, although basal VO2 was similar in control fasted and burned-fasted animals, basal VO2 in burned-fed animals was significantly greater than in control-fed animals.

Animals↗
PubMed1979

Glucose metabolism in man: responses to intravenous glucose infusion.

We have determined the effect of unlabeled glucose infusions, with and without added insulin, on glucose metabolism in normal male volunteers by means of the simultaneous primed-constant infusion of 6-3H and U-13C-glucose. Glucose kinetics were measured after 90 min of infusion. When steady state had been reached, endogenous glucose production (2.53 +/- .058 mg/kg . min, X +/- SEM) was suppressed at all rates of exogenous glucose tested (1, 2, and 4 mg/kg . min). The absolute degree of suppression was most marked (75%) at the highest rate of infusion, but the greatest degree of suppression, relative to infusion rate, was at the lowest infusion rate. The control of plasma glucose concentration during the glucose infusion was achieved primarily through regulation of endogenous Ra. The rate of uptake of glucose only increased during the 4 mg/kg . min infusion, even though there were significant elevations in the plasma glucose and insulin concentrations during the 2 mg/kg . min infusion as well. The glucose clearance rate increased only when sufficient insulin was infused with the 4 mg/kg . min glucose infusion to control the hyperglycemia that developed if no insulin was administered. Approximately 43% of the infused glucose was directly oxidized when the infusion rate was 1 or 2 mg/kg . min. That value fell to 32% when the infusion rate was increased to 4 mg/kg . min, regardless of whether insulin was infused or not.

Adult↗
PubMed1979

The natural history of hypertrophic cardiomyopathy in infants of diabetic mothers.

Eleven infants of diabetic mothers with hypertrophic cardiomyopathy have been followed for 30 to 40 months. All infants presented with cardiorespiratory distress and were found to have disproportionate septal hypertrophy on echocardiogram. Cardiac catheterization was done in four infants; three had significant subaortic obstruction. One infant had remarkable improvement after treatment with propranolol. Two infants who received digoxin did poorly and responded favorably to cessation of therapy. The natural history of HCM-IDM appears to be benign, with a resolution of symptoms within two to four weeks and a resolution of septal hypertrophy within two to 12 months. Most of the infants need only supportive care; if pharmacologic intervention is deemed necessary, propranolol appears to be the drug of choice. The natural history of this entity is that of spontaneous regression of symptoms and septal hypertrophy irrespective of therapy.

Angiocardiography↗
PubMed1979

Glucose requirements following burn injury. Parameters of optimal glucose infusion and possible hepatic and respiratory abnormalities following excessive glucose intake.

Glucose and leucine metabolism in 18 severely burned patients were studied using the primed constant infusion of U-13C-glucose and 1-13C-leucine, respectively. The leucine data were used to calculate rates of whole-body protein synthesis. In four additional burn patients and seven normal controls, the effects of exogenously infused insulin on the metabolism of infused glucose were evaluated. Also, the effect on leucine metabolism of adding insulin to infused glucose was tested and rates of protein synthesis were calculated. The protein studies were divided into two groups depending on the rate of glucose infusion. Protein synthesis was 4.3 + 0.54 g protein/kg/day during the lower infusion rates (1.4--4.5 mg/kg/min) and 5.17 + 0.19 g protein/kg/day during the higher infusion rates (4.7--9.3 mg/kg/min) (statistically different, p less than 0.05). However, when the high infusion rate group was divided into two subgroups (high, 4.7--6.8 mg/kg/min, and very high, 7.03--9.31 mg/kg/min), there was no difference in the rate of protein synthesis. When U-13C-glucose was infused during varying rates of unlabeled glucose infusion, we found that the per cent of CO2 coming from the direct oxidation of glucose rose rapidly at the lower infusion rates but reached a plateau at approximately 55% as the infusion rates exceeded 5 mg/kg/min. Addition of insulin did not affect the rate of glucose oxidation but did seem to exert a stimulatory effect on protein synthesis. It was concluded that there appears to be a maximal rate of glucose infusion, beyond which physiologically significant increases in protein synthesis and direct oxidation of glucose cannot be expected. Furthermore, there appears to be a physiological cost of exceeding the optimal glucose infusion rate, as indicated by increased rates of CO2 production during infusion as well as large fat deposits in the liver at autopsy in patients infused with large amounts of glucose.

Adolescent↗
PubMed1979

The reliability of rates of glucose appearance in vivo calculated from single tracer injections.

The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-experimental equation which describes the changes in plasma glucose specific radioactivity.

Animals↗