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Biomedical subjects

B R Bistrian

Publications and source records attributed to B R Bistrian.

At least 19 recordsLinked to original sources
PubMed1992

Tumor and host response to arginine and branched chain amino acid-enriched total parenteral nutrition. A study involving Walker 256 carcinosarcoma-bearing rats.

The metabolic effects of total parenteral nutrition (TPN) solutions containing different profiles of individual amino acids were investigated in the rats bearing Walker 256 carcinosarcoma. The rats were subcutaneously inoculated with 10(7) tumor cells and 6 days later were continuously infused intravenously for 8 days with three different TPN solutions. The experimental and control solutions were composed of high concentrations of branched chain amino acids (BCAA) and arginine (high Arg + BCAA TPN), high concentrations of BCAA (high BCAA TPN) and regular amino acids (regular TPN), respectively, and were isonitrogenous, isocaloric, and isovolemic. Rats receiving subcutaneous injection of saline rather than tumor cells received high Arg + BCAA TPN as pair-fed controls. The flooding dose method of 14C-leucine was used for the analysis of protein synthesis. With the feeding of high Arg + BCAA TPN, the tumor-bearing rats revealed a smaller increase of tumor volume and lower tumor fractional rates of growth (Kg) and synthesis (Ks) as well as protein synthesis (PS), compared with the high BCAA TPN and regular TPN in tumor-bearing rats. There were no significant differences of Ks and PS in liver and muscle between TPN groups, whereas tumor-bearing rats infused with high Arg + BCAA TPN displayed higher levels of whole-body Ks and PS than other TPN groups in tumor-bearing rats and pair-fed nontumorous rats. Except for liver RNA content which showed a lower level in tumor-bearing rats with high Arg + BCAA TPN, no other differences of DNA and RNA contents were found in tumor, liver, and muscle of the different TPN groups. The current results indicate that individual amino acids can influence tumor growth and protein metabolism, and that arginine, in combination with BCAA, may reduce tumor growth through a reduction in protein synthesis.

Amino Acids, Branched-Chain↗
PubMed1992

Influence of omega-3 fatty acids on splanchnic blood flow and lactate metabolism in an endotoxemic rat model.

Alteration in regional blood flow is important in the pathogenesis of organ failure during endotoxemia and sepsis. In particular, intestinal ischemia is thought to enhance the translocation of bacteria into the systemic circulation. We used radioactive microspheres to measure the influence of two intravenous (IV) dietary fats (vegetable oil containing high levels of omega-6 fatty acids, and fish oil containing high levels of omega-3 fatty acids) on regional blood flow during low-dose Escherichia coli endotoxin infusion (0.1 mg/100 g body weight [BW]) in a rat model. Despite absence of changes in the cardiac output, blood flow rates to the small and large intestines, stomach, and pancreas, and also to the skin and skeletal muscle were significantly reduced after 18 hours of endotoxin infusion in the rats fed standard vegetable oil. Short-term IV feeding during a period of 40 hours with an isonitrogenous, isocaloric nutrient solution containing fish oil as the only lipid source normalized intestinal perfusion and increased blood flow to the liver and spleen. Low-dose endotoxin infusion also resulted in significant increases in glucose, lactate, and pyruvate concentrations. In comparison to standard vegetable fat emulsion, fish oil significantly reduced these parameters. A second experiment was conducted to measure lactate kinetics. Based on the dilution of U-14C-lactate, fish oil feeding was associated with higher lactate clearance than standard vegetable oil feeding during the endotoxin infusion. We conclude that short-term IV feeding with fish oil improves intestinal perfusion and portal blood flow, improves glucose tolerance, and increases lactate clearance in a low-dose endotoxin rat model.

Animals↗
PubMed1992

Reevaluation of current transfusion practices in patients in surgical intensive care units.

Widespread interest in the complications associated with packed red blood cell (PRBC) transfusions has led to the scrutiny of traditional transfusion practices. Recently, attempts have been made to define more clearly the indications for PRBC transfusions in patients, particularly those who are critically ill. At present, however, transfusions continue to be ordered based on a hemoglobin level less than 10 g/dL. We report herein the impact on oxygen consumption of PRBC transfusions administered for a hemoglobin concentration less than 10 g/dL in 30 surgical intensive care unit patients who were euvolemic and hemodynamically stable. For the group as a whole, transfusion had a negligible effect on oxygen consumption. Fifty-eight percent of all such transfusions failed to change oxygen consumption by greater than 10% and could therefore be considered of questionable benefit.

Adult↗
PubMed1992

Could the oxygen cost of breathing be used to optimize the application of pressure support ventilation?

Pressure support ventilation (PSV) is a new ventilator modality that augments spontaneous inspiratory pressure with selected levels of positive airway pressure. There is presently considerable interest in its use in the management of critically ill, ventilator-dependent patients. The optimal method for application has not yet been established. This study investigated the effects of PSV on the oxygen cost of breathing (OCOB), a clinically applicable technique for quantitating the work of breathing. The OCOB and other bedside variables of pulmonary function were measured during PSV in ventilator-dependent patients where weaning was limited by an inability to sustain respiratory work. Nine studies were performed in 8 patients in the surgical intensive care unit. The OCOB, tidal volume (VT), respiratory rate (RR), and minute ventilation (VE) were measured at various levels of pressure support. The OCOB was calculated from the difference in oxygen consumption (VO2) during mechanical and spontaneous ventilation both at CPAP and with PSV. With increasing levels of PSV, the OCOB was observed to steadily decrease from 22% to 8% (p < 0.001). There were also statistically significant increases in VT and decreases in RR. VE appeared not to be influenced. The results of this study suggest that the bedside measurement of the OCOB may be an accurate, simple, and reproducible method of titrating the level of applied pressure support in order to optimize respiratory work.

Aged↗
PubMed1992

Insulin resistance versus insulin secretion in the hypertension of obesity.

We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.

Adult↗
PubMed1992

Tolerance to enteral tube feeding diets in hypoalbuminemic critically ill, geriatric patients.

Tolerance of elemental (for example, Peptamen [PEP]) or free amino acid (for example, Vivonex TEN [VIV]) tube feeding diets is controversial, especially in the critically ill patient who is hypoalbuminemic. A prospective, randomized trial was conducted to compare differences between feeding PEP (n = 8) or VIV (n = 8) in critically ill, elderly (average age of 66 years) patients. Diets were administered through nasogastric or postpyloric feeding tubes. Eleven patients had diseases of the gastrointestinal tract; all underwent surgical treatment. Patients were fed each diet at full strength, beginning with 20 to 30 milliliters per hour and advancing by 10 to 20 milliliters every day until goal rate was reached, usually on day 4. Assessment was made for ability to comply with rate of tube feeding ordered, compliance with caloric goal and tolerance (as evidenced by abdominal discomfort and diarrhea). Diarrhea was qualitatively defined as more than three stools per day and then quantitatively as the mean number of stools daily. There were no significant differences between the two groups in terms of compliance with prescribed tube feeding order or caloric goal or the presence of diarrhea and abdominal discomfort. There was a significant difference between the two groups in terms of the actual number of stools per day (PEP equals 1.38 versus VIV equals 2.25, p less than 0.02). Serum albumin concentrations upon initiation of the diets were 2.3 grams per deciliter in both groups. We conclude that tolerance to the two diets were similar because it was possible to feed enterally either PEP or VIV in critically ill, hypoalbuminemic patients (serum albumin concentrations of less than 2.5 grams per deciliter) successfully, irrespective of diet. Although there were more stools in the VIV group, this did not reduce compliance with the goals.

Aged↗
PubMed1991

Flow cytometric measurement of cell cycle kinetics in rat Walker-256 carcinoma following in vivo and in vitro pulse labelling with bromodeoxyuridine.

Flow cytometric measurements of total DNA content, cell cycle distribution, and bromodeoxyuridine (BrdUrd) uptake were made in rat Walker-256 carcinoma cells. After both in vivo and in vitro pulse labelling with BrdUrd, Walker-256 tumor cells were stained with propidium iodide (PI) to estimate the total DNA content and a monoclonal antibody against BrdUrd to estimate the relative amount of cells in S phase. BrdUrd-labelled single cell suspensions were harvested at different time intervals to determine the movement of these cells within the cell cycle. To increase BrdUrd uptake, fluorodeoxyuridine (FDU), a thymidine antagonist, was also applied in vivo and in vitro. The results indicated exponential growth characteristics for this tumor between days 5 and 8 after implantation. Tumor doubling times, derived from changes in tumor volume in vivo and from the increase in cell number in vitro were similar. The mean time for DNA synthesis was estimated from the relative movement of BrdUrd-labelled cells towards G2. The percent of cells labelled with BrdUrd and the DNA synthesis time were similar regardless of the mode of BrdUrd administration. This study demonstrates that BrdUrd labelling of rat Walker-256 carcinoma cells in vitro yields kinetic estimates of tumor proliferation during exponential growth similar to those with the administration of BrdUrd in the intact tumor-bearing rat.

Animals↗
PubMed1991

Comparative effects of omega-3 and omega-6 polyunsaturated fatty acids on protein metabolism in rats bearing the mammary adenocarcinoma.

The comparative effects of diets containing 20% (wt/wt) of either fish oil (FO) or safflower oil (SO) on protein synthesis and catabolism were determined in rats bearing the 7,12-dimethylbenz(a)anthracene (DMBA) 13762 mammary adenocarcinoma in vivo using a 6-hour constant infusion of L-(1-14C)-leucine. Tumor-bearing animals fed FO had significantly lower tumor growth rate (36 +/- 0.5 v 53 +/- 0.7%/d, P less than .05), total tumor protein synthesis (Ts) (1.25 +/- 0.1 v 1.85 +/- 0.1 mumol/h, P less than .05), and tumor protein concentration (12.0 +/- 0.5 v 14.0 +/- 0.7%/d, P less than 0.01). Tumor fractional synthetic rate and total protein breakdown rate of the tumor were unaffected by FO feeding. Both tumor-bearing and saline-control animals fed FO had significantly (P less than .01) lower liver fractional synthetic rate and total protein breakdown rate, and higher liver total protein compared with SO-fed rats. Muscle protein kinetics were unaffected by either treatment or diet. Whole body protein kinetics were not affected by dietary treatment, but the presence of tumor significantly (P less than .001) reduced whole body flux, synthesis, breakdown, and oxidation. Chronic FO feeding for 7 weeks significantly (P less than .001) lowered omega-6 polyunsaturated fatty acids (omega-6 PUFAs) and significantly elevated omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (P less than .001) in both plasma phospholipid and triglycerides. The present study indicates that dietary FO can modulate mammary tumor growth in a manner that reflects changes in protein metabolism in both host and tumor tissues.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Long-term feeding with structured lipid composed of medium-chain and N-3 fatty acids ameliorates endotoxic shock in guinea pigs.

The metabolic and physiologic responses to 7-hour endotoxin infusion (5.0 mg/kg h) were evaluated in guinea pigs following 6 weeks of dietary enrichment with diets containing either chemically structured lipid (SL) composed of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) in the form of N-3 polyunsaturated fatty acids (PUFAs), or safflower oil (SO), which is high in N-6 fatty acids. Plasma phospholipid fatty acid profiles, arterial blood pH, PCO2, PO2, HCO3, lactate, blood pressure, oxygen consumption, and energy expenditure were examined. Plasma phospholipid fatty acids profiles reflected dietary intake with SL-fed animals demonstrating a significantly higher N-3 to N-6 fatty acid ratio compared with SO-fed animals. SL-fed animals responded to endotoxemia with a mild metabolic acidosis with respiratory compensation, which was associated with moderate lactatemia (3 mmol/L). SO-fed animals developed a severe metabolic acidosis with acidemia and respiratory compensation, which was associated with hyperlactatemia (8 mmol/L, P less than .05 v SL). No differences were observed in blood pressure, oxygen consumption, energy expenditure, or respiratory quotient during endotoxemia between dietary groups compared with controls. We conclude that diets enriched with structured lipid composed of medium-chain and N-3 fatty acids can attenuate the sequelae of endotoxemia.

Animals↗
PubMed1991

Persistence of metabolic effects after long-term oral feeding of a structured triglyceride derived from medium-chain triglyceride and fish oil in burned and normal rats.

The persistence of metabolic effects following long-term oral feeding of a structured triglyceride rich in omega-3 fatty acids was studied in burned and normal rats, and compared with controls fed safflower oil, a long-chain triglyceride high in omega-6 fatty acid content. Male Sprague-Dawley rats were pair-fed a high fat diet as either structured triglyceride or safflower oil for 42 days. On day 43, a jugular catheter was placed, and rats received either a dorsal surface scald or sham injury. Following a 48-hour fast, body weight, nitrogen loss, energy metabolism, and liver weight were measured, and whole-body and tissue-specific protein kinetics were studied by constant intravenous infusion of [1-14C]leucine. Plasma albumin, free fatty acids, glucose, insulin, and triglyceride fatty acid composition were determined. Urinary nitrogen loss, energy expenditure, and plasma leucine concentration were elevated in burned rats, confirming the presence of an injury response. Rats previously fed structured triglyceride had greater liver weight, total liver protein, and percentage of leucine flux oxidized, and plasma levels of glucose and insulin were increased. Plasma leucine concentration was decreased in rats previously fed structured triglyceride. Plasma triglyceride and phospholipid fatty acid analysis showed a reduction in arachidonic acid and an increase in omega-3 fatty acids in rats previously fed structured triglyceride. Long-term feeding of structured triglyceride induced major systemic metabolic changes related to the dietary fatty acid composition that persist after the diet is discontinued.

Administration, Oral↗
PubMed1991

Structured lipid made from fish oil and medium-chain triglycerides alters tumor and host metabolism in Yoshida-sarcoma-bearing rats.

The effects of structured lipid composed of fish oil and medium-chain triglycerides (Fish/MCT) on tumor and the host metabolism was compared with conventional long-chain triglycerides (LCTs) in Yoshida-sarcoma-bearing rats receiving TPN for 3 d. The two parenterally fed groups were divided into two treatments, saline or tumor necrosis factor (TNF), given intravenously at 20 micrograms/kg body wt. Changes in tumor volume, body weight, urinary nitrogen, whole-body and tissue protein kinetics, and fatty acid composition were measured. The study revealed that Fish/MCT feeding inhibited tumor growth, which could be attributed to decreased tumor protein synthesis. Body weight and nitrogen were better maintained by Fish/MCT feeding. In addition, the effects of Fish/MCT on tumor growth were synergistic with TNF treatment. The results demonstrate that dietary fat composition can influence fatty acid compositions of tumor tissue as well as tumor protein kinetics after a short period of TPN feeding.

Animals↗
PubMed1991

Diets enriched with N-3 fatty acids ameliorate lactic acidosis by improving endotoxin-induced tissue hypoperfusion in guinea pigs.

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications.

Acidosis, Lactic↗
PubMed1991

Enhanced restoration of adenine nucleotides in rat liver following extended preservation in UW solution by provision of adenosine during reperfusion.

The extensive reduction of adenine nucleotides during preservation coupled with the loss of salvageable precursors during initial reflow may exacerbate recovery of adenine nucleotides in allograft liver following transplantation. The objective of this study was to assess whether provision of adenosine during reperfusion of rat liver stored for 20 hr in University of Wisconsin solution could enhance adenine nucleotide restoration. ATP and total adenine nucleotide content of livers perfused with an oxygenated Krebs/fluorocarbon solution containing 1 mM adenosine were restored to levels in vivo within 30 min of perfusion. Adenine nucleotide recovery in livers perfused without adenosine was only 65% of normal. Acute nutritional deprivation of the donor rats had no effect on adenine nucleotide restoration. These results indicate that a conditional deficiency of intracellular nucleotide precursors exists during initial reperfusion of liver subjected to extended storage in UW solution. Provision of supplemental adenosine to the allograft liver during initial reflow appears warranted to promote full and rapid restoration of adenine nucleotide content following extended preservation ex vivo.

Adenine Nucleotides↗
PubMed1991

Mechanisms of protein conservation during xylitol infusion after burn injury in rats: isotope kinetics and indirect calorimetry.

In order to study the mechanisms by which nutrients influence post-trauma metabolism, Sprague-Dawley rats received a 25% full-thickness burn and were randomly assigned to receive 12.5 g kg-1 bodyweight (BW) per day amino acids (AA) only, AA and 14.7 g hydrous glucose kg-1 BW per day or AA and 14.7 g hydrous xylitol kg-1 BW per day. After 4 days of hypocaloric feeding, rats receiving xylitol had a cumulative nitrogen balance of +213 +/- 82 mg N, which was significantly (P less than 0.001) better compared with either the AA with only -493 +/- 61 mg N or the AA and glucose group (P less than 0.01) with -160 +/- 101 mg N. During glucose infusion reduction of insulin-mediated fat oxidation was partially compensated by an increase in glucose oxidation. Xylitol infusions resulted in increased glucose oxidation compared with the amino acid only group without simultaneously reduced fat oxidation. Although glucose and xylitol are calorically similar, their protein sparing properties and metabolic action after injury cannot be based entirely upon their caloric equivalent.

Amino Acids↗
PubMed1991

Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth.

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of "whole body" protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.

Analysis of Variance↗
PubMed1991

Parenteral nutrient admixtures as drug vehicles: theory and practice in the critical care setting.

Parenteral nutrient (PN) admixtures are the most complex, extemporaneously compounded formulations routinely prepared for hospitalized and home-based patients. In addition, drugs are added with increasing frequency to PN admixtures, thus presenting even greater physicochemical challenges to this highly complex pharmaceutical product. The continuous infusion of selected drugs may provide pharmacokinetic and therapeutic advantages over conventional, intermittent, bolus methods of administration. Fluid conservation, cost savings, and a possible decrease in the risk of infection through reduced catheter manipulation and simplification of therapy provide additional incentives to consider the use of PN admixtures. The many advantages of PN admixtures make them an attractive approach to cost-effective care, with special clinical benefits achieved in the critical care setting. This article reviews our clinical experience using PN admixtures as drug vehicles for selected drugs and presents some theoretical as well as actual benefits associated with this practice.

Aminophylline↗