Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production.

For the first time the immunonutritional role of pyruvate on neutrophils (PMN), free α-keto and amino acid profiles, important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] as well as released myeloperoxidase (MPO) acitivity has been investigated. Exogenous pyruvate significantly increased PMN pyruvate, α-ketoglutarate, asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Moreover, increases in O(2) (-) formation, H(2)O(2)-generation and MPO acitivity in parallel with intracellular pyruvate changes have also been detected. Regarding the interesting findings presented here we believe, that pyruvate fulfils considerably the criteria for a potent immunonutritional molecule in the regulation of the PMN dynamic α-keto and amino acid pools. Moreover it also plays an important role in parallel modulation of the granulocyte-dependent innate immune regulation. Although further research is necessary to clarify pyruvate's sole therapeutical role in critically ill patients' immunonutrition, the first scientific successes seem to be very promising.

[Rupture of the internal thoracic artery 6 weeks after MIDCAB operation]. / Ruptur der A. thoracica interna 6 Wochen nach MIDCAB-Operation.

The minimally invasive coronary bypass operation is a procedure that has been firmly established in cardiac surgery for several years now. Only a few reports exist regarding the complications of this procedure. This case study reports on a 51-year-old man who collapsed 27 days after a left-sided internal mammary artery bypass on the anterior interventricular artery, when the bypass vessel ruptured. After pericardial puncture and cardiopulmonary resuscitation the patient was transported via air ambulance to a cardio-surgical center where he was successfully operated upon.

[Angioedema caused by C1-esterase inhibitor deficiency or ACE inhibitors?]. / Angioödem durch C1-Esterase-Inhibitor-Mangel oder ACE-Hemmer?

A 49-year-old woman was admitted to the intensive care ward with increasing shortness of breath due to a massive soft tissue swelling of the neck and face and a marked macroglossia. Similar symptoms were already observed earlier in the patient as well as her father, although such symptoms were never as dramatic as they were on this occasion. The patient was intubated bronchoscopically and treated unsuccessfully with cortisone, fresh plasma und C1-esterase inhibitor. The patient only first reported intake of an ACE inhibitor a few days after the acute episode, which was most probably the causative factor given that serum C1 and C4 complement factors were almost normal.

Alterations in neutrophil (PMN) free intracellular alpha-keto acid profiles and immune functions induced by L-alanyl-L-glutamine, arginine or taurine.

The objective of this study was to determine the dose as well as duration of exposure-dependent effects of L-alanyl-L-glutamine, arginine or taurine on polymorphonuclear neutrophil (PMN) free alpha-keto acid profiles and, in a parallel study, on PMN immune functions. Exogenous L-alanyl-L-glutamine significantly increased PMN alpha-ketoglutarate, pyruvate PMN superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase (MPO) activity. Arginine also led to significant increases in alpha-ketoglutarate, pyruvate, MPO release and H2O2 generation. Formation of O2- on the other hand was decreased by arginine. Incubation with taurine resulted in lower intracellular pyruvate and alpha-ketobutyrate levels, decreased O2- and H2O2 formation and a concomitant significantly increased MPO activity. We therefore believe that considerable changes in PMN free-alpha-keto-acid profiles, induced for example by L-alanyl-L-glutamine, arginine or taurine, may be one of the determinants in cell nutrition that considerably modulates the immunological competence of PMN.

Serum creatinine and perioperative outcome--a matched-pairs approach using computerised anaesthesia records.

BACKGROUND AND OBJECTIVE: A study was designed to utilise the resources of our computerised anaesthesia record keeping system to assess the attributable effects of increased preoperative creatinine (> 1.3 mg dL(-1)) on outcome in patients undergoing non-cardiac surgery. METHODS: This retrospective study was based on data sets of 58 458 patients recorded with a computerised anaesthesia record keeping system over a period of 4 yr at a tertiary care university hospital. Cases were defined as patients with a preoperative creatinine > 1.3 mg dL(-1); controls (creatinine < or = 1.3 mg dL(-1)) were selected and automatically matched according to several parameters (ASA physical status, high risk and urgency of surgery, age and gender) in a stepwise fashion. Main outcome measures were hospital mortality and the incidence of intraoperative cardiovascular events. RESULTS: Three-thousand-and-twenty-eight patients (5.2%) had preoperative creatinine values > 1.3 mg dL(-1). Matching was successful for 54.5% of the cases, leading to 1649 cases (mean creatinine 3.3 +/- 2.2 mg dL(-1)) and 1649 controls (1.0 +/- 0.2 mg dL(-1)). The crude mortality rates for the cases and matched controls were 2.2% (n = 36) and 0.9% (n = 15), respectively (P = 0.003). Intraoperative cardiovascular events were found in 30.1% of the patients (n = 496) and in 28.3% of the matched controls (n = 466; P = 0.25, power = 0.46). Using logistic regression analyses a significant association between preoperative increased creatinine and hospital mortality was found (odds ratio 2.62; 95% confidence interval [1.39; 4.931). CONCLUSIONS: An increased preoperative serum creatinine in patients undergoing non-cardiac surgery is associated with an increased perioperative risk, but not with a higher incidence of intraoperative cardiovascular events.

Benzodiazepine receptor-dependent modulation of neutrophil (PMN) free amino- and alpha-keto acid profiles or immune functions.

We have examined the effects of midazolam, Ro 5-4864 (agonist for "peripheral" [p] benzodiazepine receptors [BR]), PK 11195 (antagonist for pBR), flumazenil (antagonist for "central" BR), naloxone (antagonist for opiate receptors) and the combination of midazolam and Ro 5-4864, PK 11195, flumazenil or naloxone on intracellular amino- and alpha-keto acids and the immune function markers superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)) and released myeloperoxidase (MPO) activity in neutrophils (PMN). Only midazolam and Ro 5-4864 led to significant changes in the dynamic PMN free amino- and alpha-keto acid pools. Concerning PMN immune function markers, midazolam and Ro 5-4864 significantly decreased O(2)(-) and H(2)O(2) formation and released MPO. When midazolam and Ro 5-4864 were applied together they appeared to act additively. Pre-incubation with PK 11195 partially neutralized the midazolam effects whereas flumazenil or naloxone showed no effects. We therefore believe that pBR are involved in the signal transmission of anesthetic-induced cellular metabolic changes in PMN.

Effects of ornithine on neutrophil (PMN) free amino acid and alpha-keto acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of ornithine on polymorphonuclear leucocyte (PMN) free amino- and alpha-keto acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Exogenous ornithine significantly increased PMN asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, alpha-ketoglutarate and pyruvate as intracellular ornithine increased. Concerning PMN immune function markers ornithine increased H2O2-generation and MPO activity while O2- -formation was decreased. We believe therefore that ornithine is important for affecting PMN "susceptible free amino- and alpha-keto acid pool" although the mechanisms are not yet clear. This may be one of the determinants in PMN nutrition considerably influencing and modulating PMN host defense capability.

Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery.

OBJECTIVE: Cardiopulmonary bypass is often associated with pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated plasma levels of pro- and anti-inflammatory cytokines in survivors and non-survivors from MODS in the early postoperative course following open heart surgery. DESIGN: Prospective clinical study. SETTING: A University Cardiothoracic Intensive Care Unit. METHODS: Levels of cytokines (IL-6, IL-8, IL-10, IL-18, and TGF- ) and procalcitonin (PCT) were measured at the first four postoperative days in 16 adult male patients with an Apache II-score >24 and two or more organ dysfunctions after myocardial revascularization. MAIN RESULTS: All pro-inflammatory cytokines, except for IL-6, were significantly elevated in non-survivors from MODS, with peak values at the first two postoperative days. The plasma levels of immunoinhibitory cytokines showed no differences between the groups. CONCLUSIONS: The results of our study show a different expression of pro-inflammatory cytokines in survivors and non-survivors from MODS following operations with extracorporeal circulation. In addition to Apache-II score, especially IL-8, IL-18, and PCT may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery.

Effects of arginine, L-alanyl-L-glutamine or taurine on neutrophil (PMN) free amino acid profiles and immune functions in vitro.

The objective of this study was to determine the effects of arginine, L-alanyl-L-glutamine (Ala-Gln) or taurine on polymorphonuclear leucocyte (PMN) free amino acid profiles, superoxide anion (O2-) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase activity (MPO). Arginine led to significant increases in PMN arginine, ornithine, citrulline, aspartate, glutamate and alanine concentrations as well as increased H2O2-generation and MPO activity while O(2-)-formation was decreased. Ala-Gln caused significant increases in PMN free glutamine, alanine, asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine concentrations and increased PMN immune functions. Taurine significantly increased PMN free taurine profiles, reduced PMN neutral amino acid content and decreased H2O2- and O(2-)-formation while MPO was increased. Altogether, the pharmacological regimens which enhance the supply of arginine, Ala-Gln or taurine in whole blood significantly affect PMN "susceptible free amino acid pool". This may be one of the determinants in PMN nutrition considerably influencing PMN immune functions. Introduction Polymorphonuclear leucocytes (PMN) ensure an important part of non-specific cell-mediated immunity and play a crucial role in the host defense

Pharmacokinetics of antibiotic prophylaxis in major orthopedic surgery and blood-saving techniques.

The pharmacokinetics of cefuroxime, cefotiam, cefamandole, and ampicillin/sulbactam were randomly measured in 40 patients undergoing major orthopedic surgery associated with high blood and volume turnover and intraoperative blood salvage. Serum and bone concentrations and the pharmacokinetics occurring in the context of these procedures were measured. No changes in elimination half-life relative to a normal population occurred with cefuroxime, cefotiam, and ampicillin. Serum and tissue concentrations were slightly lower with cefamandole and sulbactam, but reapplication of the initial dose was required with all antibiotics 4 hours after the first application.

Impairment of renal function after cardiopulmonary bypass is not influenced by dopexamine.

INTRODUCTION: The objective of this study was to evaluate the effects of dopexamine on renal function in 4 groups of patients either with or without renal dysfunction. Transient renal dysfunction is often not clinically relevant in patients with normal renal function, but it is an important clinical factor in patients with pre-existing renal failure. Dopexamine (DX) is a commonly used catecholamine which probably exerts a selective effect at the splanchnic bed. MATERIAL AND METHODS: 24 patients with normal renal function and 24 patients with impaired renal function (creatinine in serum > or = 1.5 mg/dL) were each randomly allocated to 2 groups. Group 1 (control) without renal dysfunction and group 3 (control/dysfunction) with renal dysfunction were considered as control groups, while the patients in DX and DX/dysfunction groups received 1 microg/kg/min dopexamine until the end of surgery. Kidney function was investigated using standard parameters and by investigating specific proteins and enzymes. RESULTS: All patients showed pathologic excretions of the investigated parameters during cardiopulmonary bypass (CPB) with no differences between the study groups. The distal tubule, the lysosomal regions, Henle's loop and the glomerular tuft were all damaged. Heart rate and cardiac index increased significantly in the DX-groups, first until the end of surgery, second until the start of ECC. CONCLUSION: Dopexamine at a dose of 1 microg/kg/min had no influence on renal function and protein excretion and cannot be regarded as a kidney function protecting substance.

Methohexital affects neutrophil (PMN) dynamic free amino acid pool and immune functions in vitro.

BACKGROUND AND OBJECTIVE: The objective of this study was to determine the dose as well as the duration of exposure-dependent effects of methohexital on neutrophil [polymorphonuclear leucocyte (PMN)] free amino acid profiles and, in a parallel study, on PMN immune functions. METHODS: Whole blood samples were taken from 20 volunteers and incubated with methohexital [0 (control), 3.6, 26, 130 and 260 microg mL-1] for 10, 30, 60 or 120 min. PMN amino acid profiles were documented using advanced PMN separation and high-performance liquid chromatography procedures. Superoxide anion (O2-) and hydrogen peroxide production (H2O2), and activity of released myeloperoxidase (MPO), were determined photometrically. RESULTS: After methohexital, significant dose (> or = 26 microg mL-1) as well as duration of exposure-dependent (> or = 30 min) increases in histidine, isoleucine, leucine, valine, methionine, serine, glycine, threonine, and decreases in glutamine, glutamate, aspartate, asparagine, arginine, ornithine, citrulline, alanine and taurine were observed (P < or = 0.05). Concerning PMN immune functions, methohexital significantly decreased O2-, H2O2 formation and MPO (> or = 26 microg mL-1, > or = 30 min, P < or = 0.05). CONCLUSIONS: Altogether, there is significant relevance to the pharmacological regimens which enhance the supply of methohexital in whole blood. In regards to our results, we suggest that considerable changes in PMN 'dynamic free amino acid pool', for example induced by methohexital, may be one of the determinants in cell nutrition adversely affecting PMN metabolism. It is partially through its effect on the PMN free amino acid pool that maleficent pharmacological stress may have an unintentional influence on PMN immune functions.

Hydroxyethyl starch (HES) does not directly affect renal function in patients with no prior renal impairment.

STUDY OBJECTIVES: To examine the effects of hydroxyethyl starch (HES) on renal function. DESIGN: Randomized, controlled trial. SETTING: Operating theatre of a university hospital. PATIENTS: 60 ASA physical status I and II male patients undergoing middle ear surgery. INTERVENTIONS: Patients received either lactated Ringer's solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringer's solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour. MEASUREMENTS: Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously. MAIN RESULTS: There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups. CONCLUSIONS: Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation.

Treatment of sepsis in cardiac surgery: role of immunoglobulins.

Cardiopulmonary bypass (CPB) is associated with an injury that may cause pathophysiological changes such as systemic inflammatory response syndrome, multiple organ dysfunction syndrome, and mediator-induced multiorgan failure. Systemic endotoxinaemia, release of proinflammatory cytokines, and interactions between neutrophils and endothelium have been reported to correlate with a high incidence of organ dysfunction, infection and sepsis following cardiac surgery. This review discusses the dysregulation of the immune response as a major reason for the higher susceptibility to infections following cardiac surgery, various treatment strategies to reduce CPB-induced inflammation, and especially the prophylactic use of immunoglobulins in cardiac surgery.

Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-L-glutamine supplementation.

The objective of this study was to determine the effects of diazepam, L-alanyl-L-glutamine (ala-gln) or diazepam combined with ala-gln on polymorphonuclear leukocyte (PMN) free amino acid profiles. In a parallel study the effects on PMN immune functions were also documented for the first time. The incubation of whole blood with diazepam led to significant changes in PMN free glutamine, aspartate, glutamate, ornithine, arginine, citrulline, taurine and methionine as well as branched chain and neutral amino acid concentrations. Ala-gln caused significant increases in PMN glutamine and alanine and asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine profiles. Regarding PMN immune functions, diazepam significantly decreased superoxide anion (O(2)(-)) and hydrogen peroxide production (H(2)O(2)) and myeloperoxidase activity (MPO) while ala-gln significantly increased PMN immune functions. Ala-gln supplemented to diazepam largely reversed the changes in PMN amino acid profiles and PMN immune functions brought about by diazepam. Overall, diazepam or ala-gln lead to significant changes in PMN free amino acids. Important PMN immune functions also seem to be affected. In regards to the results, there is significant relevance to the pharmacological regimens which enhance the supply of diazepam or ala-gln in whole blood suggesting that considerable changes in PMN "labile free amino acid pool" occur. These regimens often follow beneficial nutritional therapy or maleficent pharmacological stress and may be one of the determinants in cell nutrition which influence PMN function. It is partially through its effect on PMN labile free amino acid pool that ala-gln supplemented to diazepam may maintain PMN immune functions in vitro.

Conscientious metabolic monitoring on a patient with hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome undergoing anaesthesia.

Currently we know not more than 50 patients who show an interesting combination of increased plasma ornithine concentrations, postprandial hyperammonemia, and homocitrullinuria (HHH-syndrome). Since exact knowledge of this severe, although rare syndrome is important for any perioperative or intensive medical treatment concerning therapy and progression of the disease, we report a comprehensive study on a 32-year old woman with this rare multifaceted disorder who had to undergo general anaesthesia. For the first time amino acid status in plasma, urine, cerebrospinal fluid and especially polymorphonuclear leucocytes, which in the investigation showed to be valuable tool for evaluating amino acid metabolism in nucleated cells in HHH-syndrome, and further important pathophysiologic indicators of cellular and metabolic function have been conscientiously investigated and compared. The pathophysiological repercussions of our results as well as the recommendations for conscientious therapeutical management are discussed.

The effects of thiopentone on free intracellular amino acids in polymorphonuclear leucocytes.

Previous studies have shown the inhibitory effects of thiopentone on polymorphonuclear leucocyte (PML) function. However, major biochemical mechanisms which have been involved are still unknown. The aim of this study was therefore to investigate thiopentone's effects on intracellular amino acid metabolism in PML using both advanced PML separation- and HPLC techniques, especially developed for this purpose and precisely validated in our institute. Overall, our study indicates important dose-dependent alterations of free intracellular amino acid metabolism following thiopentone treatment and draw attention to the biochemical mechanisms which may be involved in both thiopentone-induced modulation in PML function and cellular immunocompetence.

Effects of etomidate on free intracellular amino acid concentrations in polymorphonuclear leucocytes in vitro.

BACKGROUND: Previous studies have shown the inhibitory effects of etomidate on polymorphonuclear leucocyte (PMN) function. No reports exist, however, regarding free intracellular amino acid metabolism, although physiological cell metabolism and basic cell functions rely upon a balanced intracellular amino acid content and the cell membrane-mediated separation of cellular amino acids from the extracellular plasma amino acid pool. Thus, in the current study, we evaluated the effects of etomidate on free intracellular amino acid metabolism in PMN. METHODS: With ethics committee approval, blood was withdrawn from 35 healthy volunteers and incubated (1 h) either with 0 microg/ml, 0.0156 microg/ml, 0.0625 microg/ml or 0.5 microg/ml of etomidate as well as with its additives (propylene glycol and Lipofundin MCT 10%). The PMN were separated using standardized Percoll-gradient and centrifugation procedure before deep-freezing and lyophilization techniques were employed. All PMN samples were dissolved in methanol/H2O, and the concentrations of free intracellular amino acids were monitored using both novel advanced PMN-separation and high-performance liquid chromatography techniques. RESULTS: Etomidate influenced important free amino acid profiles in PMN in a dose-dependent manner, indicating complex changes of cellular amino acid turnover. Neither propylene glycol nor Lipofundin MCT 10% changed free amino acid concentrations in PMN. CONCLUSIONS: For the first time, the effects of etomidate on free intracellular amino acid metabolism in PMN have been investigated. Our results draw attention to the biochemical pathways which may be involved in etomidate-induced alterations in PMN function and cellular immunocompetence.

Dysregulation of immune response following neurosurgical operations.

BACKGROUND: Postoperative infections are common and potentially fatal complications in neurosurgical intensive care medicine. An impairment of immune function has been described after central nervous system surgery and in patients harboring malignant brain tumors. The aim of our study was to investigate whether differences in cell-mediated immunity can be found in patients undergoing craniotomy for surgery of glioblastoma or clipping of an intracerebral aneurysm. METHODS: In order to determine the influence of the underlying disease on the immune system, we measured changes in cytokine concentrations (IL-6, IL-10, TGF-beta1) and lymphocyte-subsets (CD3+, CD3+HLA-DR+, CD4+, CD8+, CD19+, and CD16+56+) in 8 patients with glioblastoma and in 8 patients with an intracerebral aneurysm before, during and after the neurosurgical procedure. RESULTS: In the comparison of glioblastoma and aneurysm patients, we could show that IL-6 plasma levels were pre- and intraoperatively higher in the aneurysm-group (P<0.05), and the plasma concentrations of IL-10 and TGF-beta were significantly elevated in the glioma-group. The lymphocyte-subsets showed a significantly lower percentage of NK-cells and activated T-cells in the glioma-group. CONCLUSION: Our results document a significant dysregulation of immune response in glioma patients. This may be induced by elevated plasma concentrations of immunoinhibiting cytokines IL-10 and transforming growth factor-beta 1.