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Biomedical subjects

M Georgieff

Publications and source records attributed to M Georgieff.

At least 217 records · Page 12Linked to original sources
PubMed1993

Effect of phenylephrine bolus administration on left ventricular function during high thoracic and lumbar epidural anesthesia combined with general anesthesia.

The effect of phenylephrine (PHE) boluses on left ventricular (LV) function was examined in patients without cardiovascular disease who developed arterial hypotension during high thoracic epidural anesthesia (TEA) combined with general anesthesia (GA) (group 1) or lumbar epidural anesthesia (LEA) combined with GA (group 2). LV function was assessed by transesophageal echocardiography (TEE) before and after central venous injection of 1 microgram/kg PHE. Fractional diameter shortening (FDS), end-systolic wall stress (ESWS), and rate-corrected velocity of circumferential fiber shortening (mVcfc) were determined. PHE effectively restored arterial blood pressure in both groups with a peak effect between 30 and 45 s after injection. FDS was reduced from 38% to 25% (mean, P < 0.01) in group 1 and remained unchanged in group 2. ESWS increased from 70 to 143 x 10(3) dyne.cm-2 (P < 0.01) and from 57 to 86 x 10(3) dyne.cm-2 (P < 0.05), in groups 1 and 2, respectively. mVcfc was significantly reduced from 1.11 to 0.80 circ/s (P < 0.05) in group 1 and was not altered in group 2. The authors conclude that PHE given as an intravenous bolus to patients under high TEA plus general anesthesia causes a transient impairment of LV function.

Abdomen↗
PubMed1993

The effect of phenylephrine bolus administration on left ventricular function during isoflurane-induced hypotension.

By using transesophageal echocardiography, we examined the effect of phenylephrine (PHE) bolus administration on left ventricular function in 16 patients with no known cardiovascular disease during isoflurane-induced hypotension. PHE was compared with norepinephrine (NE). The patients received an intravenous bolus of PHE (2 micrograms/kg) or NE (0.1 microgram/kg) in random order. The second substance was administered after levels of arterial blood pressure and heart rate returned to baseline levels. We determined fractional area change, end-systolic wall stress, and rate-corrected mean velocity of circumferential fiber shortening. Both substances effectively restored arterial blood pressure. However, after PHE, fractional area change decreased from 0.45 to 0.31 (mean) and rate corrected mean velocity of circumferential fiber shortening from 0.88 to 0.57 circumference/s, whereas both variables remained unchanged in response to NE. End-systolic wall stress increased after PHE and NE from 47.4 to 91.2 and from 54.0 to 65.2 10(3) dyne/cm2, respectively. We conclude that phenylephrine, given as intravenous bolus to patients under isoflurane hypotension, causes a transient impairment of left ventricular systolic performance.

Adult↗
PubMed1993

Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration.

To determine absorption characteristics of endotracheal lidocaine, we administered lidocaine to hemodynamically stable patients by different techniques. Blood samples were taken for measurement of lidocaine plasma concentrations (fluorescence polarization immunoassay), and pharmacokinetics were calculated by regression analysis. Plasma concentrations at 1.5 and 2 min after drug administration were higher (P < 0.05) after instillation into the endotracheal tube (1.40 +/- 0.19 and 1.26 +/- 0.14 microgram/mL) than after deep endobronchial administration (1.00 +/- 0.08 and 0.83 +/- 0.05 microgram/mL). A biphasic absorption with a division of the area under the curve (AUCtot) into two parts (AUC1 and AUC2) could be assumed. After tube instillation, the AUC1/AUCtot ratio (2.6%) was higher (P < 0.05) than after deep endobronchial instillation (1.1%). To achieve high plasma concentrations within a short time, AUC1, representing a nearly instantaneous absorption, seems to be more important than AUC2, representing a higher but delayed absorption (depot effect). Because deep endobronchial lidocaine administration accentuated the late absorption, presumably by preventing drug distribution to the whole lung, this technique was detrimental to obtaining high plasma concentrations within a short period of time.

Adult↗
PubMed1993

Evidence for inverse regulation of high and low affinity binding sites for (-)125iodocyanopindolol in human mononuclear leucocytes during epinephrine infusion.

As we have shown earlier (-)125Iodocyanopindolol (125ICYP) binding to beta-adrenoceptors (beta-AR) in human mononuclear leucocytes (MNL) yields evidence for the existence of high affinity (Bhiaff) and low affinity (Bloaff) binding sites. We studied the regulation of these 2 classes of binding sites during 240 min of (-)-epinephrine (EPI) infusion (0.1 microgram/kg/min) (n = 8) in male healthy volunteers. Saturation experiments were performed on MNL membranes with 125ICYP over a large concentration range (1-550 pmol/l). Binding parameters were calculated by computer analysis assuming 2 classes of binding sites. We found a preinfusion value of 830 +/- 50 [sites/cell] (KD = 1.5 +/- 0.2 pmol/l) of Bhiaff binding sites and 5210 +/- 510 [sites/cell] (KD = 420 +/- 80 pmol/l) of Bloaff. During EPI infusion we observed biphasic modulation of the Bhiaff and an inverse modulation of the Bloaff. After 40 min of EPI Bhiaff increased to 1970 +/- 280 [sites/cell] (KD = 4.2 +/- 0.8 pmol/l), whereas Bloaff decreased to 2720 +/- 280 [sites/cell] (KD = 140 +/- 70 pmol/l); despite constant plasma epinephrine concentration (PEC) after 240 min of EPI Bhiaff changed to 1310 +/- 240 [sites/cell] (KD = 2.8 +/- 1.0 pmol/l) vs. 4370 +/- 760 [sites/cell] (KD = 190 +/- 100 pmol/l) Bloaff. These results suggest an interdependent inverse modulation of the 2 classes of binding sites for 125ICYP on MNL during EPI infusion.

Binding, Competitive↗
PubMed1993

A partially automated radioligand binding assay system for use in clinical and pharmaceutical research.

Using a Tecan robotic sample processor and IBM compatible PCs we have developed a flexible, partially automated radioligand binding assay system. It handles pipetting parameters of up to 16 saturation or competition experiments at a time with up to 24 radioligand- or competitor-concentrations in a range over 4 orders of magnitude per experiment. The system provides enough flexibility so that all pipetting parameters including different tube-, rack-sizes, sample volumina and pipetting sequences may be easily adapted to the large variety of experimental requirements in binding assays. It rationalizes and increases assay throughput (up to 70% spare of working time), improves reliance and reproducibility of results. Radioactive exposure is minimized to the time preparing the radioligand working solution and transferring the sample tubes to and from the sample processor. The system has proven effective in various investigations on binding interactions, as well as in clinical studies on receptor expression under physiologic, pathological and therapeutic conditions.

Binding, Competitive↗
PubMed1993

Effects of xylitol on carbohydrate and protein metabolism after trauma and during sepsis.

INTRODUCTION: Total parenteral nutrition (TPN) after trauma and during sepsis has two major goals. One is the reduction of increased protein catabolism, the second is to avoid hyperglycemia and enhanced hepatic gluconeogenesis. Glucose and xylitol differ in their utilization rates after trauma and during sepsis. Whole-body glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects on hepatic glucose production and protein sparing, we conducted two animal and two clinical studies. METHODS: For the analysis of glucose and protein turnover radioactive and stable isotope techniques were applied. In burned rats primed constant infusions of 6-[3H]-glucose, 1-[14C]-alanine, 3-[14C]-alanine and U-[14C]-acetate were used to determine whole body glucose turnover, gluconeogenesis from C3-precursors and alanine flux. In septic rats nitrogen balance was calculated after determination of 24-hour-urine nitrogen content measured by micro-Kjeldahl digestion. 24-hour urinary 3-methyl-histidine excretion was analysed by amino acid autoanalyser. In human studies hepatic glucose production and urea synthesis rates were measured using primed continuous infusions of [6,6-d2]-glucose and [2-N15]-urea, respectively. RESULTS: In the first trauma model we demonstrated that hypocaloric xylitol in contrast to glucose significantly reduced hepatic glucose production and gluconeogenesis from C3-carbons. In the septic rat exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated nitrogen retention and lower 3-methyl-histidine excretion. In two studies on surgical intensive care patients we were able to confirm these nitrogen sparing properties of xylitol. Hepatic glucose production and urea synthesis rates were significantly reduced during xylitol infusion after trauma, whereas equicaloric glucose had no effects. In septic patients xylitol led to significant lower lactate concentrations and gluconeogenesis rates than isocaloric glucose. DISCUSSION: In animal as well as in human studies hypocaloric xylitol and the mixture of glucose/xylitol (1:1) were more efficient in preserving body protein than glucose alone. Hepatic gluconeogenesis was significantly reduced when compared to isocaloric glucose. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg BW/d by xylitol. During long-term TPN a glucose/xylitol mixture (1:1) in a dosage of 6 g/kg BW/d is recommended together with amino acids and, if necessary, lipids.

Animals↗
PubMed1993

[A comparison of different endotracheal tubes. Tracheal cuff seal, peak centering and the incidence of postoperative sore throat].

UNLABELLED: The study objective was to evaluate cuff seal, tube tip position and incidence of postoperative sore throat in three different endotracheal tubes: the reusable Rüsch "red rubber" tube (low-volume, high-pressure cuff) and the disposable Rüsch "Super Safety Clear" and Mallinckrodt "lo-pro" tubes (both high-volume, low-pressure cuffs). METHODS: In a prospective randomized trial, 150 consecutive patients scheduled for minor orthopaedic surgery under standardized general anaesthesia, including standardized cuff pressure control, were allocated to one of the three types of endotracheal tube. Leakage and intratracheal tube tip position were investigated by means of fiberoptic tracheoscopy via the endotracheal tube, preceded by pharyngeal instillation of indigocarmine. The semi-standardized interviews for the recording of postoperative sore throat were performed once a day under double-blind conditions from the day of operation to postoperative day 3. Statistical independence testing was based on the chi 2-test, significance was assumed at P < 0.05. MAIN RESULTS: A past-cuff leakage of the pharyngeally instilled dye was found in three patients with "red rubber" tubes. In all of these cases the tracheal cross section deviated markedly from circular. The tips of the "Super Safety Clear" tubes tended to be better centred (P = 0.099). Bad tip position, however, had little influence on postoperative throat complaints (P = 0.394). The differences in incidence of postoperative throat complaints between the "red rubber" (48.9%), "Super Safety Clear" (35.6%) and "lo-pro" tubes (34.1%) did not reach the 5% level (P = 0.288). Such complaints, however, were significantly more frequent in females and in obese patients who exceeded their Broca weights by more than 25%. By contrast, postoperative throat complaints did not vary statistically significantly by age group, tracheal cross-sectional shape, use of atropine or duration of intubation. CONCLUSION: Despite the economic (usable up to 100 times) and ecological (less PVC waste) advantages of the rubber tube, the disposable tubes with high-volume, low-pressure cuffs tended to be superior regarding cuff seal, tube tip position and incidence of postoperative throat complaints. Nevertheless, the continued use of "red rubber" type reusable tubes may be justified in cases where the tube has to stay in place for only a short time.

Adult↗
PubMed1993

[New aspects of parenteral nutrition of septic patients].

A major goal of this review article is to show that nutritional physiology in normal man is rather different from patients bearing an inflammatory response. Known nutrients and a variety of energy sources reveal pharmacological actions during such metabolic circumstances. An understand of the pathophysiologic state of sepsis is essential for adequate nutritional support especially in this patient population.

Energy Metabolism↗
PubMed1992

[Carbohydrate and lipid metabolism following heart bypass operations. The effect of the intravenous hypocaloric administration of glucose versus glucose xylitol (1:1)].

The effect of glucose-xylitol infusion on carbohydrate and lipid metabolism was investigated in 18 metabolically normal men (mean age 56.1 [35-65] years) with coronary heart disease after they had undergone a coronary artery bypass operation. During the first postoperative hours, group I (n = 6) received glucose only (2 mg/kg.min), group II (n = 6) glucose+xylitol (1 mg/kg.min each), and group II a glucose-containing electrolyte solution (0.83 mg/kg.min glucose). Blood glucose and insulin concentrations during the infusion period were significantly (P < 0.05) lower in groups II and III than I (glucose after 6 h: group I 21.5 [15.3-26.8] mmol/l; group II 14.2 [11.2-18.1] mmol/l; group III 12.6 [6.8-16.0] mmol/l). The highest lactate concentrations were reached in group I, 6 hours after the operation. Palmitine and stearine, as well as oleic and linoleic acid concentrations were significantly lower 12 hours postoperatively in group I than groups II and III (P < 0.05). These data indicate that energy-ineffective high glucose concentrations were avoided and endogenous lactate production reduced by the postoperative infusion of glucose+xylitol. In addition, it achieved a higher supply of free fatty acids as energy source to the myocardium without reaching toxic concentrations in the postischaemic myocardium.

Adult↗
PubMed1992

Stress hormone response during and after cardiopulmonary resuscitation.

The purpose of this study was to assess whether plasma adrenocorticotropin, cortisol, vasopressin, and renin concentrations are higher in resuscitated than in nonresuscitated patients during cardiopulmonary resuscitation, and whether there are possible correlations between these hormones and blood pressure or heart rate in the immediate postresuscitation phase. Of 34 consecutive patients (36-85 yr of age) with out-of-hospital cardiac arrest, 20 could be successfully resuscitated and admitted to hospital, whereas in the remaining 14 patients restoration of spontaneous circulation could not be achieved. During cardiopulmonary resuscitation, median adrenocorticotropin, cortisol, vasopressin, and renin concentrations in the external jugular vein were 237 pg/ml, 32.6 micrograms/dl, 122 pg/ml, and 46.5 ng/l, respectively, in resuscitated patients, and 45 pg/ml (P = 0.018), 18.4 micrograms/dl (P = 0.481), 88 pg/ml (P = 0.049), and 11 ng/l (P = 0.017), respectively, in nonresuscitated patients. Median adrenocorticotropin, cortisol, vasopressin, and renin concentrations were 101 pg/ml, 34.6 micrograms/dl, 22 pg/ml, and 25 ng/l, respectively, 60 min after successful resuscitation. No significant correlations were found between hormone levels and blood pressure or heart rate, but there was a significant negative correlation between the interval from collapse to the start of cardiopulmonary resuscitation and plasma cortisol concentrations during cardiopulmonary resuscitation (Spearman rank correlation coefficient = -0.967, P less than 0.001), indicating an impaired cortisol release from the adrenal cortex. The lower hormone concentrations of the nonresuscitated patients measured during cardiopulmonary resuscitation might indicate an impairment in neuroendocrine response.

Adrenocorticotropic Hormone↗
PubMed1992

[A study of the parameters of the delivered tidal volume. Ventilation on a lung model using the CICERO anesthetic ventilator].

In many anaesthesia ventilators in common use, the tidal volume delivered is different from the tidal volume preset on the respirator. Tidal volume delivered by mechanical ventilation during anaesthesia may be influenced by fresh gas flow (FGF), the respiratory rate (RR) or the inspiratory: expiratory ratio (I:E). This may cause inadequate hypo- or hyperventilation in small children, especially in newborns and neonates. Using small tidal volumes from 20 to 100 ml preset on the respirator, we investigated in a lung model the tidal volumes delivered by the anaesthesia ventilator CICERO (Dräger, FRG) with variations of FGF, RR and I:E. MATERIAL AND METHODS. The anaesthesia ventilator CICERO (software version 4.16) was equipped with the low-compliance tubes of the "Ulmer Kinder-Set" (Rüsch Co.) and the regular CO2 canister (1500 ml) of the machine. The circuit was connected to a lung model consisting of a glass clyinder filled with copper wool with a compliance of 3.3 ml/mbar. To create a pressure-volume correlation of the entire system, i.e. the lung model, the anaesthesia circuit and the ventilator, calibrated glass syringes were used and the pressure increase in the test lung was measured. This pressure-volume correlation was linear. The pressure increase in the lung model caused by the tidal volume during ventilation therefore reflected the actual tidal volume delivered. The study was performed with small tidal volumes from 20 to 100 ml that could be adjusted exactly on the ventilator. Delivered tidal volumes were studied by varying the FGF from 1 to 6 l/min and the RR from 20 to 60/min (with I:E = 1:1.5) and by varying the RR from 20 to 60/min and the I:E from 2:1 to 1:3 (with FGF = 21/min). RESULTS. By varying FGF, RR and I:E no changes in delivered tidal volumes were noted. In all settings of the ventilator studied, the delivered tidal volume was similar to the desired tidal volume preset on the ventilator. The highest deviation from the delivered tidal volume to the tidal volume preset was 17.5% with a tidal volume of 20 ml. In preset tidal volumes 30-100 ml this deviation was lower than 10%. An intermittent "auto-PEEP" up to 5 mbar was noted during high respiratory rates (50 and 60/min) combined with an I:E at 2:1 and 1:1 or with a FGF at 4 or 6 l/min. The compliance of the ventilator equipped with the circuit was 4.2 ml/mbar. CONCLUSION. The findings in this study prove that with tidal volumes ranging from 20 to 100 ml the actual tidal volume delivered by the anaesthesia ventilator CICERO is equivalent to the tidal volume set on the machine regardless of the variation of FGF, RR and I:E. These findings are mainly based on two circumstances. Firstly, fresh gas flow is fed into a reservoir and not added to the volume delivered by the bellow during inspiration as in many other respirators. Secondly, the CICERO works with a compliance correction function integrated into the machine. Computed compressible volume from the circuit and the ventilator is added to the tidal volume preset on the ventilator; therefore, the volume delivered by the bellow consists of the volume set on the ventilator plus the compressible volume. With these characteristics the anaesthesia ventilator CICERO meets important requirements for a ventilator in paediatric anaesthesia. However, for final assessment further clinical studies are required.

Anesthesiology↗
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

[Artificial feeding].

An infusion rate above 3 g/kg BW per day glucose leads to a reduction of oxidative metabolism of the energy sources glucose, free fatty acids, and exogenous triglycerides. Simultaneously splanchnic lipogenesis is stimulated and visceral protein utilization inhibited. During the 1st to 4th day after trauma Xylitol (3 g/kg BW per day) is superior to glucose with regard to oxidative metabolism of energy sources and stimulation of visceral protein synthesis. A comparable metabolic effect can be achieved by a glucose/xylitol mixture (1:1); (6 g/kg BW per day) during long-term nutrition.

Blood Glucose↗
PubMed1991

[The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol].

Total parenteral nutrition (TPN) after trauma and sepsis has two major goals. One is the reduction of enhanced protein catabolism; the second is the avoidance of enhancement of whole-body glucose turnover. Glucose and xylitol differ in their quantitative utilization rate after trauma and sepsis. Maximal glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects with regard to whole-body glucose turnover rate of gluconeogenesis and protein sparing, we conducted two studies using animal models and two clinical studies. METHODS. For the determination of glucose and protein turnover, radioactive and stable isotope techniques were applied. In an animal model a primed constant infusion of 3-H-6-glucose, 14-C-1-alanine and 13-C-3-alanine and 14-C-U-acetate was used to determine total glucose appearance, gluconeogenesis from 3-C-precursors and alanine flux. In the human studies hepatic glucose production was determined by using a primed constant infusion of 6.6-D-2-glucose and urea synthesis rate was determined by a primed constant infusion of 2-N-15-urea. RESULTS. In the first rat model we were able to show that hypocaloric xylitol compared to glucose significantly reduced whole-body glucose turnover from 1741 +/- 232 mumol/h during glucose infusion to 449 +/- 49 mumol/h during xylitol infusion and gluconeogenesis from C-3 carbons form 382 +/- 24 mumol/h during glucose infusion to 155 +/- 39 mumol/h during xylitol infusion after a burn trauma. In a second septic rat model the exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated N-balance from +144 +/- 90 mgN/kg body weight per day during glucose infusion to +699 +/- 80 mgN/kg body weight per day during glucose-xylitol infusion and a reduced 3-methyl-histidine excretion from 7.14 +/- 0.61 mumol/kg body wt. per day during glucose infusion to 4.10 +/- 0.56 mumol/kg per day during glucose-xylitol infusion, respectively. In two studies with surgical intensive care patients we were able to confirm the nitrogen-sparing properties of xylitol infusion, together with amino acids during hypocaloric feeding or during TPN with a glucose/xylitol mixture in a proportion of 1:1. From a basal urea production rate of 9.2 +/- 1.6 mumol/kg min. xylitol led to a significant reduction with 6.4 +/- 1.5 mumol/kg per min. Hepatic glucose production was significantly reduced during xylitol infusion from basal 4.8 +/- 0.6 mg/kg per min to 3.1 +/- 0.7 mg/kg per min, respectively. Equicaloric glucose in a dosage of 3 g/kg per day had no effect. During TPN glucose/xylitol, in a proportion of 1:1 at a total dosage of 0.24 g/kg per h, significantly reduced whole-body glucose turnover, endogenous glucose production and lactate concentrations compared to an isocaloric glucose infusion. DISCUSSION. In animal as well as in human studies hypocaloric xylitol as well as a glucose-xylitol mixture were more efficient in preserving body protein than glucose alone. Whole-body glucose turnover was significantly reduced during hypocaloric xylitol or glucose-xylitol infusion compared to isocaloric glucose infusion. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg body wt. per day using xylitol. During long-term TPN, a glucose-xylitol mixture in a proportion of 1:1 in a dosage of 3 g/kg body wt. per day each is recommended as energy source, together with amino acids and, if necessary, lipids.

Animals↗