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Biomedical subjects

D P Katz

Publications and source records attributed to D P Katz.

At least 19 recordsLinked to original sources
PubMed2002

Impact of sepsis, lung injury, and the role of lipid infusion on circulating prostacyclin and thromboxane A(2).

OBJECTIVE: To investigate whether plasma levels of prostacyclin (PGI2) and thromboxane A(2) (TxA2) are a function of the infusion rate of soybean-based fat emulsions, severity of systemic inflammation, and pulmonary organ failure. DESIGN: Prospective, randomized, crossover study. SETTING: Intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients, ten presenting with severe sepsis, eight with SIRS or sepsis complicated with ARDS. INTERVENTIONS: Patients were randomly assigned to receive rapid fat infusion over 6 h (rFI) or slow fat infusion over 24 h (sFI) along with parenteral nutrition. MEASUREMENTS AND RESULTS: The stable prostanoids 6-keto-PGF1alpha and TxB2 were measured in arterial and mixed venous blood samples, and at 6-h periods trans-pulmonary balances (TPB) were calculated. Free linoleic acid fraction was determined in arterial blood. rFI induced greater increase of linoleic acid than sFI in both groups. Enhanced prostanoid levels and correlations with linoleic acid availabilities were found, however, in ARDS patients only, revealing the highest sepsis- and lung injury scores. Averaged TPB per 24 h was positive in the sepsis group and negative in the ARDS group as rFI induced lowest TPB values for TxB2 at 6 h. CONCLUSION: The quantity of prostanoids formed and their subsequent utilization are dependent on the availability of precursor linoleic acid and are probably affected by the severity of SIRS or sepsis and the existence of pulmonary organ failure, respectively. Because TxA2 might be extracted by the injured lung, rapid infusion of soybean-based fat emulsions should be avoided in patients suffering from severe pulmonary organ failure.

Adult↗
PubMed2001

Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis.

OBJECTIVE: To investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I2/thromboxane A2 in arterial blood, pulmonary hemodynamics, and gas exchange. DESIGN: Prospective, controlled, randomized, crossover study. SETTING: Operative intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS). INTERVENTIONS: Patients were assigned randomly to receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B2 and 6-keto-prostaglandin-F1alpha plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostaglandin-F1alpha/thromboxane B2 ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index increased as well, whereas pulmonary vascular resistance and Pao2/Fio2 declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin-F1alpha or thromboxane B2 and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(a-a)o2/Pao2 decreased after rapid fat infusion, whereas Pao2/Fio2 increased. CONCLUSION: Pulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin I2 and thromboxane A2 may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.

APACHE↗
PubMed1999

Branched-chain amino acid-induced hippocampal norepinephrine release is antagonized by picrotoxin: evidence for a central mode of action.

Previous studies indicated that administration of a 1:1:1 mixture of the branched-chain amino acids leucine, isoleucine, and valine (BCAA) decreased the response to pain. The present study investigates the effects of BCAA on release of norepinephrine (NE) from isolated hippocampal brain slices. BCAA evoked 3H-NE release in a concentration-dependent manner. This effect was antagonized by the gamma aminobutyric acid (GABA) receptor antagonist picrotoxin, again in a concentration-dependent manner, suggesting that the effect may be mediated via a GABA receptor. Given the role of NE and of GABA receptors in the central response to pain, it is possible that the BCAA may exert their antinociceptive properties through activation of GABA receptors.

Amino Acids, Branched-Chain↗
PubMed1996

The antinociceptive effects of branched-chain amino acids: evidence for their ability to potentiate morphine analgesia.

The effect of branched-chain amino acids (BCAA) on pain threshold was studied in rats. Nociception was induced by the hot-plate analgesia meter, a method measuring supraspinally organized pain responses. After a single intravenous injection of BCAA (320 mg/kg), the percent change in latency time to the pain response significantly increased by 19% in 60 min, and by 22% in 75 min (p < 0.005), as compared to an injection of an equal volume of a standard concentration of an amino acid solution or physiological saline. Subsequently, we studied the interaction of BCAA with opioid-type analgesia. In combination with intravenously injected morphine (3 mg/kg), BCAA significantly potentiated and prolonged the action of morphine using the hot-plate test. From 5 min after morphine injection, the latencies to a pain response were markedly higher with the combination of BCAA and morphine (+80% and +89% at 5 min after morphine injection, if BCAA was administered 45 or 60 min prior to morphine injection, respectively) when compared with the effect of morphine alone (+13% at 5 min; p < 0.005). BCAA demonstrated analgesic effects, which, in combination with morphine, potentiated and prolonged the antinociceptive action of morphine. BCAA may represent a new adjunct treatment modality for acute and chronic pain, and give us further insight into the mechanisms of pain control.

Amino Acids, Branched-Chain↗
PubMed1996

Parenteral use of medium-chain triglycerides: a reappraisal.

Over the last two decades, the clinical use of intravenous fat emulsions for the nutritional support of hospitalized patients has become routine. During this time long-chain triglycerides (LCT) derived from soybean and/or safflower oils were the exclusive lipid source for these emulsions, providing both a safe calorically dense alternative to dextrose and essential fatty acids needed for biologic membranes and the maintenance of immune function. During the past decade, the availability of novel experimental triglycerides for parenteral use has generated interest in the use of these substrates for nutritional and metabolic support. Medium-chain triglycerides (MCT), long advocated as a superior substrate for parenteral use, possess many unique physiochemical and metabolic properties that make them theoretically advantageous over their LCT counterparts. Although not yet approved in the United States, preparations containing MCT have been widely available in Europe. Intravenous MCT preparations, either as physical mixtures or structured lipids, have been used clinically in patients with immunosuppresion, critical illness, liver and pulmonary disease and in premature infants. Despite great promise, the clinical data comparing the efficacy of MCT-based lipid emulsions to their LCT counterparts has been equivocal. This may be due in part to the limited nature of the published clinical trials. Measures of efficacy for parenteral or enteral nutritional products has taken on new meaning, in light of the reported experience using immunomodulatory nutrients. Current concerns about cost of medical care and resource use warrant careful deliberation about the utility of any new and expensive therapy. Until clinical data can fulfill expectations derived from animal studies, it is difficult to advocate the general use of MCT-based lipid emulsions. Future clinical studies with MCT-based emulsions should have clear outcome objectives sufficient to prove their theorized metabolic superiority.

Animals↗
PubMed1996

The use of an intravenous fish oil emulsion enriched with omega-3 fatty acids in patients with cystic fibrosis.

The effects of parenteral nutrition supplemented with a lipid emulsion enriched with the omega-3 fatty acids (FA), eicosapentaenoate (20:5n-3) and docosahexaenoate (22:6n-3), derived from fish oil were compared to a standard lipid emulsion containing omega-6 FA in patients with cystic fibrosis (CF). Patients were randomized to receive either Omegavenous 10%, which contains fish oil (IFO), or Liposyn III 10% (control) daily for 1 mo at a dose of 150 mg/kg. There were no observed allergic or toxic reactions, no abnormalities in liver function tests or coagulation parameters. To assess the bioavailability of the lipid administered, measurement of plasma free fatty acid (FFA) levels were made of the essential FA. There were no adverse changes in plasma levels of the omega-6 FA (18:2n-6, 18:3n-6, 20:3n-6, and 20:4n-6), and plasma levels of the omega-3 FA (20:5n-3 and 22:6n-3) increased significantly during the 1-mo study. There were no significant changes in plasma FFA profiles of the essential FA for the patients receiving the control lipid. The effect of treatment on pulmonary function was also investigated. There were no significant changes in FVC, FEV1, PEFR, FEV1/ FVC, or FEF25-75 (absolute value or percentage) over the 4 weeks of study in the group receiving IFO or control. This preliminary investigation suggests that intravenous administration of fish oils enriched with long chain omega-3 FA to patients with CF is safe and bioavailable.

Adolescent↗
PubMed1996

Splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction syndrome.

The incidence of multiple organ failure syndrome (MOFS) has increased dramatically in most intensive care units (ICU) in the United States and is now the leading cause of death after sepsis, trauma, and burns (1). Despite advances in resuscitation, availability of potent antibiotics, and modern techniques of organ support (2), the survival of critically ill patients with MOFS has not significantly improved since the syndrome was first described over 2 decades ago (3). In the ICU, the monitoring and management of critically ill patients with MOFS has relied, in large part, on readily available measurements of global hemodynamics and oxygen transport. Given the increased understanding of the special role of splanchnic hypoperfusion in the pathophysiology of sepsis and MOFS (4-5), investigators have focused more recently on regional blood flow and oxygen metabolism in these patients (6). In this article, we first present a clinical overview of sepsis and MOFS. Current concepts of the pathogenesis and pathophysiology of MOFS are discussed, with particular emphasis on the roles of splanchnic ischemia and gut barrier failure in the development of both sepsis and the maintenance of the systemic inflammatory response that leads to MOFS. Alterations in both global and regional oxygen transport in septic shock are described to emphasize the limitations of global monitoring in the assessment of splanchnic tissue oxygenation. The role of gastric tonometry in the monitoring of splanchnic oxygenation and its utility in critically ill patients is then analyzed. In addition, the effects and clinical implications of commonly used vasoactive agents on intestinal oxygenation are discussed. Finally, novel therapeutic strategies based on the "gut-origin hypothesis" of MOFS are reviewed.

Animals↗
PubMed1995

Effect of substrate manipulation on reducing ischemia/reperfusion injury in isolated perfused rat hearts.

The objective of this investigation was to assess the effect of substrate manipulation on reducing ischemia/reperfusion injury (IRI). Isolated rat hearts were perfused with modified Krebs-Henseleit buffer containing either (in mM): glucose 11 (G1), glucose 22 (G2), or glucose 11 with either xylitol 11 (GX), mannitol 11 (GM), L-leucine 1 (GL), or L-glutamic acid 2 (GGA), respectively. Hearts were subjected to 10 min of global no-flow ischemia, followed by 20 min of reperfusion. Mean tissue perfusion, oxygen consumption, and peak left ventricular pressure (PLVP) were determined at baseline, in the first minute of regular heart rhythm following ischemia, and after 20 minutes of reperfusion. Reperfusion arrhythmia (in sec) was significantly (all p < 0.05) shorter in GGA (115 +/- 33) vs G1 (315 +/- 29) and G2 (273 +/- 33), and also in GL (161 +/- 26) vs G1. Dry/wet heart weight ratios were also greater in GGA (0.20), when compared with G2 (0.16), GX (0.17), GM (0.17), GM (0.17), and GL (0.17) (all p < 0.02), suggesting less cellular/interstitial edema. Percent recovery in PLVP was improved (p < 0.03) in GL (81 +/- 2) and GGA (81 +/- 2) vs. G2 (71 +/- 3), without significant alterations in oxygen consumption. Thus, cardiac IRI can be diminished by substrate manipulation, especially by augmentation of glutamate and leucine, most likely due to an improved anaerobic energy generation and utilization.

Journal Article↗
PubMed1991

Branched-chain amino acid in chronic renal failure patients: respiratory and sleep effects.

Sleep disorders, including a high incidence of sleep apnea, have been recognized as a significant problem in chronic renal failure (CRF) patients. In a preliminary study, we examined CRF patients on maintenance hemodialysis for three nights; one control night, and thereafter randomized to infusion of saline (placebo) for one night and 4% branch-chain amino acid (BCAA) solution for one night. Polysomnographic and respiratory data [respiratory rate, oxygen saturation and end-tidal CO2 (ETCO2)] was recorded continuously throughout the nights and data from each hour compared with baseline (awake) values. The patients studied were characterized by reduced sleep quality and decreased amount of rapid eye movement (REM) sleep. The BCAA infusion was associated with a return of REM sleep to normal and a significant decrease in ETCO2 during both REM and non-REM sleep (P less than 0.05). Our findings demonstrate respiratory stimulation during sleep with infusion of BCAA; this stimulatory effect on respiration (in contrast to many respiratory stimulants) is associated with an increased amount of REM sleep.

Adult↗
PubMed1988

Effects of sodium bicarbonate in canine hemorrhagic shock.

We studied the use of sodium bicarbonate administration in a canine model of hemorrhagic shock to determine its effect on hemodynamics, arterial and venous blood gases, respiratory gases, and blood lactate levels. Thirteen dogs were anesthetized, paralyzed, mechanically ventilated, and hemodynamically monitored. Hypotension was induced and maintained at a mean arterial pressure of 40 to 45 mm Hg using controlled hemorrhage and reinfusion. After 2.5 h of shock, the dogs were randomized into two groups: one group (n = 6) received NaCl infusion; the other (n = 7) received sodium bicarbonate (1 mEq/kg followed by a continuous infusion of 2.5 mEq/kg.h for 2.5 h). CO2 production was increased in the alkali group, but there was no statistically significant difference between groups in any measured hemodynamic, blood gas, or respiratory gas variable. These included heart rate, BP, cardiac output, arterial and venous pH, CO2 production, and bicarbonate levels. Blood lactate levels, however, in the bicarbonate treated animals were significantly (p less than .01) higher than in the group treated with NaCl alone (10.1 +/- 3.2 vs. 5.1 +/- 1.2 mEq/L). These results are similar to the effects of bicarbonate found in other models of lactic acidosis, and suggest that bicarbonate therapy may have limited usefulness in the treatment of lactic acidosis.

Acidosis, Lactic↗
PubMed1987

The effect of medium and long chain triglyceride on human adipose tissue metabolism.

Studies have been performed to assess the effects, in vivo and in vitro, of lipid emulsions on human adipose tissue prostaglandin production. Subcutaneous adipose tissue obtained either during elective surgery or by needle aspiration was studied in tissue culture or by using a perifusion apparatus. Physical mixtures of emulsions of long chain triglyceride (LCT) and/or medium chain triglyceride (MCT) were added to the tissue culture medium so that the final concentration was 400 mg/dl. After a 3-day incubation period the tissue was harvested, placed in buffer and used to determine in vitro production of prostaglandin E2, prostacyclin I2 (measured as its stable end product 6-keto PGF1 alpha) and thromboxane A2 (measured as TXB2) by radioimmunoassay. The results demonstrated that samples incubated in 100% MCT had the most significant increase in prostaglandin production, while those incubated in 100% LCT had the most significant decrease in activity of the three prostaglandins assayed. The addition of LCT to MCT caused a stepwise decrease in adipose tissue prostaglandin production. The data suggest a pharmacological rather than a physiological effect of lipid emulsions containing MCT and/or LCT on adipose tissue prostaglandin production. In vivo effects of a 20% safflower oil emulsion, containing high levels of the essential fatty acid linoleate, were assessed in five pediatric patients. Adipose tissue was obtained before and after two and four weeks of treatment. Fatty acid profiles and prostaglandin production were determined. The results demonstrated that intravenous fat infusion increased the concentrations of linoleic and arachidonic acids found in adipose tissue within a short interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1982

Circulating factors affect 6-phosphofructokinase activity in human adipose tissue.

6-Phosphofructokinase activity was lower in adipose tissue of obese, insulin-resistant subjects studied at stable body weight than in nonobese controls. This difference was absent during weight loss due to an increase in 6-phosphofructokinase activity in the obese subjects; the change suggested possible regulation by circulating factors. In an initial test of this hypothesis, blood serum collected from obese subjects at stable weight and incubated with adipose tissue in vitro produced lower 6-phosphofructokinase activity than did sera from nonobese controls.

Adipose Tissue↗