Biomedical subjects

Andreas Hoeft

Publications and source records attributed to Andreas Hoeft.

At least 19 recordsLinked to original sources

PubMed2006

Hypertonic saline during CPR: Feasibility and safety of a new protocol of fluid management during resuscitation.

BACKGROUND AND PURPOSE: In experimental studies infusion of hypertonic saline during cardiopulmonary resuscitation (CPR) increased resuscitation success rate and improved myocardial and cerebral reperfusion during CPR. We tested the feasibility and the safety of this new therapeutic measure in a randomised, preclinical pilot study. METHODS: The study was performed in the EMS system of Bonn after approval of the local ethical committee. Study inclusion criteria were out-of-hospital cardiac arrest (CA) of non-traumatic origin, age > or =18 years, application of adrenaline (epinephrine) during CPR, duration of CA < or = 15 min, and estimated body weight < or = 125 kg. Patients randomly received 2 ml/kg/10 min HHS (7.2% NaCl with 6% hydroxy ethyl starch 200,000/0.5 [HES]) or HES alone. Haemoglobin, blood gases, plasma sodium and potassium concentrations were measured before and 10 min after infusion, and after admission to hospital. Feasibility and safety of the new fluid management was evaluated by looking for side effects and determination of resuscitation success and admission rates. RESULTS: Sixty-six patients were included. After infusion of HHS, plasma sodium concentration increased to 168+/-29 mmol/l at 10 min after application but already decreased to near normal (147+/-5.5 mmol/l) at admission to hospital. Patients receiving HHS showed a trend to higher resuscitation success and hospital admission rates (ROSC: HHS 66.7%, HES 51.5%, p = 0.21; admission: HHS 57.6%, HES 39.4%, p = 0.14). The benefit of HHS was more pronounced if duration of untreated CA was >6 min or if initial rhythm was asystole or pulseless electrical activity (PEA). Negative side-effects were not observed after HHS. CONCLUSIONS: HHS after CA is feasible and safe and might improve short term survival after CPR. However, whether giving HHS could be a useful measure to increase resuscitation success after out-of-hospital CA requires a larger preclinical trial.

Aged↗

PubMed2006

Genomic variations and transcriptional regulation of the human mu-opioid receptor gene.

The mu-opioid receptor (MOR1) is a target of endogenous and exogenous opioids and plays a pivotal role for anesthesia and analgesia. Variations in the 5' flanking sequence of the mu-opioid receptor gene may influence transcriptional regulation and ultimately alter protein expression of MOR1. In the present study we investigated the influence of eight single nucleotide polymorphisms (SNP) within the mu-opioid receptor promoter on promoter activity and evaluated the frequencies of the relevant SNPs in 700 patients under opioid medication. Reporter-gene-constructs were created by means of PCR and site directed mutagenesis, testing eight SNPs previously described. The neuroblastoma cell line SHSY5Y was used for transfection and promoter activity was estimated by luciferase activity. Of the eight reporter gene constructs employed to test genomic variations, two produced a significant change in luciferase activity when compared to wild-type constructs. The G-554A variation located within a known NFkB binding element resulted in a decreased activity whereas the A/G base exchange at position -1320 showed an increased luciferase activity. This particular variant generated a myeloid zinc finger (MZF1) cis-acting element known to impact transcription. The allele frequency of the -1320G variant was 0.21% in 700 Caucasian patients under opioid medication in contrast to 9.1% reported previously in drug addicted African Americans. Because of this unexpected low frequency an association analysis to opioid requirements and effects of mu-opioid receptor agonists was not feasible. In conclusion, transcriptional regulation of MOR1 is modified by two genetic variations at positions -554 and -1320 of the mu-opioid receptor promoter. Individuals presenting these variations may have an altered level of MOR expression. A possible association of these genomic variants on efficacy and side effects of opioid treatment in different ethnic groups has to be elucidated.

5' Flanking Region↗

PubMed2006

Toll-like receptor 4 modulates myocardial ischaemia-reperfusion injury: Role of matrix metalloproteinases.

UNLABELLED: Toll-like receptor 4 (TLR4) mediates innate immune responses following endotoxemia and myocardial ischaemia-reperfusion (I/R) injury. Pre-treatment with the major TLR4 ligand lipopolysaccharide (LPS) reduces infarct size. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play a crucial role in endotoxemia possibly also determining I/R injury. AIMS: We investigated the influence of TLR4 on infarct size and assessed the influence of MMP and TIMP regulation on I/R injury. METHODS: Left anterior descending artery (LAD) occlusion was performed on wild-type (C3H/HeN) and TLR4-deficient (C3H/HeJ) mice. Animals were stimulated with LPS (1 mg/kg) or PBS 16 h ahead of 60 min LAD ligation. After 24 h of reperfusion, triphenyltetrazolium chloride staining was performed and infarct size was measured by planimetry. MMP- and TIMP-mRNA expression were determined by RPA after 3 h of reperfusion. MMP zymographic activity was monitored 6 h after occlusion. RESULTS: TLR4-deficient mice and LPS-treated wild-type mice showed significantly reduced infarct areas. LPS-stimulation significantly increased the overall MMP/TIMP mRNA expression ratio due to elevated MMP-3, -8, -9, and TIMP-1 in wild-type mice. I/R overall reduced the MMP/TIMP ratio due to increased MMP-1, TIMP-1, and -3 mRNA expression. CONCLUSIONS: LPS pre-treatment and TLR4-deficiency led to a decreased infarct size. However, infarct area and MMP/TIMP ratio were not correlated. This means that in TLR4-deficient mice MMP/TIMP ratios are not determining the infarct size.

Animals↗

PubMed2006

Myocardial injury modulates the innate immune system and changes myocardial sensitivity.

OBJECTIVE: Transverse aortic constriction (TAC) results in a transient increase of proinflammatory cytokines, which return to baseline levels within 3 d. In contrast to cytokine baseline levels, the myocardium remains capable to respond even stronger to a new stimulus. As the molecular mechanisms for this phenomenon are unknown, we tested whether TAC modulates the innate immune system in mice and changes the inflammatory reaction to a new stimulus. METHODS: Following 3 d of TAC or sham-operation procedure (SOP), LPS (20 mg/kg) or PBS (control) were administered intraperitoneal for 10 min as well as for 6 h. Hemodynamic parameters were recorded to measure the effects of TAC and LPS. After TAC/SOP alone CD14 expression was monitored and after additional 6 h of LPS/PBS the expression of CD14, TLR4 and proinflammatory cytokines were determined by western-blot, ELISA and RNase protection assay, respectively. Following TAC/SOP and 10 min of LPS/PBS, NFkappaB activation was investigated by EMSA. RESULTS: TAC induced cardiac hypertrophy and elevated blood pressure. LPS application led to hypotension and other symptoms of sepsis. CD14 expression increased after TAC alone and even further after additional LPS challenge. However, we did not detect changes of TLR4 expression. Also NFkappaB activation increased after LPS challenge higher in the TAC than in the SOP group. LPS-stimulation induced also higher cytokine expression in the TAC than in the SOP group. CONCLUSION: TAC modulates innate immunity by regulating the expression of CD14 and changes the myocardial tissue to respond more powerful to LPS.

Animals↗

PubMed2006

Toll-like receptor 4, nitric oxide, and myocardial depression in endotoxemia.

The molecular mechanisms that mediate gram-negative sepsis-associated myocardial dysfunction remain elusive. Myocardial expression of inflammatory mediators is Toll-like receptor 4 (TLR4) dependent. However, it remains to be elucidated whether TLR4, expressed on cardiac myocytes, mediates impairment of cardiac contractility after lipopolysaccharide (LPS) application. Cardiac myocyte contractility, measured as sarcomere shortening of isolated cardiac myocytes from C3H/HeJ (with nonfunctional TLR4) and C3H/HeN (control), were recorded at stimulation frequencies between 0.5 and 10 Hz and after incubation with 1 and 10 mug/mL LPS for up to 8 h. Control cells treated with LPS were investigated with and without a competitive LPS inhibitor (E5564) and a specific inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea. In control mice, LPS reduced sarcomere shortening amplitude and prolonged duration of relaxation, whereas sarcomere shortening of C3H/HeJ cells was insensitive to LPS. NFkappaB and iNOS were upregulated after LPS application in control mice compared with C3H/HeJ. Inhibition of TLR4 by E5564 as well as inhibition of iNOS prevented the influence of LPS on contractile activity in control myocytes. LPS-dependent suppression of cardiac myocyte contractility was significantly blunted in C3H/HeJ mice. Competitive inhibition of functional TLR4 with E5564 protects cardiac myocyte contractility against LPS. These findings suggest that TLR4, expressed on cardiac myocytes, contributes to sepsis-induced myocardial dysfunction. E5564, currently under investigation in two clinical phase II trials, seems to be a new therapeutic option for the treatment of myocardial dysfunction in sepsis associated with endotoxemia.

Animals↗

PubMed2006

Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of beta-defensin-2 in rats.

Beta-defensin-2 (BD-2), a small cationic antimicrobial peptide, was first described to be an inducible defensin at the epithelial surfaces. In vitro studies have demonstrated that it may play a pivotal role in the anti-inflammatory immune response in addition to its antimicrobial activity. The purpose of this study was to evaluate the effect of overexpression of BD-2 on lung injury to crudely investigate whether the function of BD-2 in the lung attributed to both antimicrobial action and modulation of the immune response. Recombinant adenovirus carrying an expression cassette of rat BD-2 or control adenovirus carrying empty vector was administered intratracheally to Sprague-Dawley rats 48 h before performing acute lung injury, which was induced either by Pseudomonas aeruginosa infection or by cecal ligation and double puncture (2CLP). In vivo antimicrobial activity of BD-2, histological changes of the lungs in both infectious and 2CLP models, pulmonary intracellular adhesion molecule-1 protein level, as well as the 7-day survival rate in the latter model were determined. Amounts of the P. aeruginosa in the lung with BD-2 overexpression were significantly lower compared with that in controls (2.87+/-0.76x10(4) colony-forming units [CFU]/mL vs. 2.49+/-0.74x10(6) CFU/mL, P<0.05). Overexpression of BD-2 reduced alveolar damage, interstitial edema, and infiltration of neutrophils in both models. Furthermore, in the 2CLP model, recombinant BD-2 not only significantly decreased protein levels of intracellular adhesion molecule-1 in lung tissue at 24, 36, and 72 h after 2CLP (P<0.05), but also significantly improved the survival of rats (P<0.05). The CFU of abdominal bacteria was comparable to that in the control rats (P>0.05). Therefore, overexpression of BD-2 protects against P. aeruginosa pneumonia and 2CLP-induced lung injury based on its antimicrobial and anti-inflammatory activities, respectively. Modulating the expression level of BD-2 may serve as an approach to attenuate lung injury.

Animals↗

PubMed2006

The performance of a target-controlled infusion of propofol in combination with remifentanil: a clinical investigation with two propofol formulations.

Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery lasting longer than 1 h received a combined TCI of propofol (Marsh parameter set; propofol randomly either dissolved with long- or middle-/long-chain triglycerides) and remifentanil. Arterial propofol plasma concentrations and hemodynamic and derived electroencephalogram variables were determined at various stages before, during, and after surgery. Measured propofol plasma concentrations exceeded the predicted values by 59%, and 48% when recalculated with the Schnider parameter set. Pharmacokinetic population analysis showed a small central volume of distribution (3.55 L) and reduced clearance (1.31 L/min) for propofol. ASA status and sex were the only variables that had a significant influence on propofol pharmacokinetics. In a second step, a new pharmacokinetic variable set for propofol was determined in the first 27 patients. Post hoc performance analysis of the remaining 27 patients showed improved accuracy using the new variable set. Our results show that when remifentanil and propofol are combined, the Marsh and Schnider parameter sets systematically underestimate propofol plasma concentrations. Presented, in part, at the Annual Meeting of the European Society of Anesthesiologists, Amsterdam, The Netherlands, June 1, 1999, and the Annual Meeting of the American Society of Anesthesiologists, Dallas, Texas, October 12, 1999.

Anesthetics, Combined↗

PubMed2006

Spectral entropy and bispectral index as measures of the electroencephalographic effects of propofol.

Recently, Datex-Ohmeda introduced the Entropy Moduletrade mark for measuring depth of anesthesia. Based on the Shannon entropy of the electroencephalogram, state entropy (SE) and response entropy (RE) are computed. We investigated the dose-response relationship of SE and RE during propofol anesthesia in comparison with the Bispectral Indextrade mark (BIS). Twenty patients were studied without surgical stimulus. Anesthesia was induced by a constant propofol infusion of 2000 mg/h (451 +/- 77 microg x min(-1) x kg(-1)) via a large forearm vein. Propofol was infused until substantial burst suppression occurred (more than 50%) or mean arterial blood pressure decreased to <60 mm Hg. Hereafter, infusions were stopped until recovery of BIS values up to 60 was reached. Subsequently, the constant propofol infusion of 2000 mg/h was restarted to increase depth of anesthesia and again decreased (infusion was stopped) within the BIS value range of 40-60. The coefficient of determination (R2) and the prediction probability (P(K)) were calculated to evaluate the performance of SE, RE, and BIS to predict changing propofol effect-site concentrations. R2 values for SE, RE, and BIS of 0.88 +/- 0.08, 0.89 +/- 0.07, and 0.92 +/- 0.06, respectively, were similar. The calculated P(K) values, however, revealed a significant difference between SE and RE compared with BIS, with P(K) = 0.77 +/- 0.09, 0.76 +/- 0.10, and 0.84 +/- 0.06, respectively. BIS seems to show slight advantages in predicting propofol effect-site concentrations compared with SE and RE, as measured by P(K) but not as measured by R2.

Adult↗

PubMed2005

Screening of copy number polymorphisms in human beta-defensin genes using modified real-time quantitative PCR.

Defensins are cationic antimicrobial peptides, which play an important role in host immune defense to some infectious diseases as well as immune disease and skin disease. Recent studies identified that the genes coding for human beta-defensin 2 (DEFB4), human beta-defensin 3 (DEFB103) and human beta-defensin 4 (DEFB104) showed variation in copy numbers. This variation may have an impact on gene expression levels. Here, we have demonstrated a real-time PCR-based method to measure beta-defensin gene copy number. Using this relative real-time quantitative PCR, we developed a new rapid and reliable approach, which involves amplification of the target locus (DEFB4 or DEFB103 or DEFB104) and the single-copy reference locus (human serum albumin, ALB) in a single PCR reaction. A calibrator was prepared by recombining one copy of the target gene and one copy of the reference gene into a plasmid. After correcting the PCR amplification efficiency, which differed between the defensin gene and ALB gene, and normalization by the calibrator, the ratio of the copy number of the target gene to that of the reference gene in an unknown sample was determined. This normalized ratio directly related to the gene copy number. The assay was validated using previously genotyped samples, which demonstrated high accuracy and reliability of the method. Furthermore, this method was used to screen the copy number variations of these three beta-defensin genes in healthy blood donors. This method proved to be a reliable and fast tool to genotype gene copy number variations in projects associating genomic variations with gene expression or with population phenotypes in epidemiologic studies.

Base Sequence↗

PubMed2005

Intracellular detection of macrophage migration inhibitory factor in peripheral blood leukocytes.

The oxidoreductase MIF is currently discussed as a new promising target of immunomodulatory therapy in patients with severe sepsis. An increasing body of evidence attributes an important role especially to intracellular MIF for regulation of endotoxin responsiveness as well as regulation of nuclear transcription factors. Up to now, measurement of MIF relied on ELISA techniques, lacking the ability to directly measure intracellular MIF and distinguish between different leukocyte subpopulations. Therefore, we developed a sensitive and robust flow cytometry-based method to reliably detect intracellular levels of MIF. This method can readily be applied in cultured cells as well as in subsets of human leukocytes in whole blood. Intracellular MIF content of whole-blood leukocyte subsets is detected simultaneously, and is individually determined for T-lymphocytes, B-lymphocytes, macrophages, and granulocytes, respectively. When tested in an ex vivo whole-blood stimulation system using PMA/Ionomycin the intracellular MIF content doubled in CD3+ T-lymphocytes and increased threefold in CD14+ macrophages. Baseline intracellular MIF levels of different leukocyte subpopulations were quantified in 22 healthy blood donors. Baseline intracellular MIF levels in T-lymphocytes are twice as high compared to those in B-lymphocytes and macrophages.

Enzyme-Linked Immunosorbent Assay↗

PubMed2005

Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.

BACKGROUND: Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG. METHODS: In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications. RESULTS: As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03). CONCLUSIONS: The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.

Administration, Oral↗

PubMed2005

Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aortocoronary bypass graft surgery. METHODS: In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aortocoronary bypass graft surgery patients received either heparinase I (maximum 35 microg/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was predefined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (> or = 30 mmHg decrease) and/or pulmonary hypertension (> or = 40 mmHg with an increase > or = 10 mmHg) within 30 min of heparin reversal initiation. RESULTS: Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery. CONCLUSIONS: Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.

Adolescent↗

PubMed2004

The correlation of the bispectral index with propofol effect site concentrations is not altered by epochs indicated as artefact-loaded by narcotrend.

OBJECTIVE: Artefact detection is an essential feature of automatic EEG monitoring systems used in anaesthesia. Clinical experience indicates that Narcotrend monitoring (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) excludes more EEG epochs because of artefacts than bispectral index monitoring (BIS, Aspect Medical Systems, Newton, MA, version XP). Whether this increased exclusion of epochs is justified has not been investigated yet. METHODS: Eighteen adult patients undergoing radical prostatectomy were investigated. Induction of anaesthesia was performed with a fentanyl bolus and a propofol infusion. Additionally, following intubation patients received 15 ml bupivacaine 0.5% epidurally. After a waiting period of 45 min depth of anaesthesia was varied two times by increasing and decreasing propofol concentrations. Narcotrend index, BIS values and calculated propofol effect site concentrations were automatically recorded at intervals of 5 s. We tested the hypothesis whether exclusion of artefacts detected by the Narcotrend monitor would possibly improve the prediction probability of the BIS monitor, justifying the necessity of artefact suppression. RESULTS: Simulated propofol effect site concentrations ranged from 2 microg/ml to 6 microg/ml. The Narcotrend monitor excluded a significantly higher percentage of epochs because of artefact detection (12.6 + 1.0%) than the BIS monitor (0.4 +/- 0.1%). The performance of BIS as an indicator of predicted propofol effect site concentrations did not differ when including (P(K) = 0.86 +/- 0.05) or excluding (P(K) = 0.85 +/- 0.04) the data pairs where Narcotrend monitor but not BIS monitor indicated an artefact. Artefacts were evenly distributed over the investigated range ofpropofol effect site concentrations. CONCLUSION: Exclusion of data pairs that were detected as artefacts by Narcotrend but not by BIS did not change the performance of bispectral index as an indicator of propofol effect site concentration.

Aged↗

PubMed2004

Effects of hypertonic versus isotonic infusion therapy on regional cerebral blood flow after experimental cardiac arrest cardiopulmonary resuscitation in pigs.

OBJECTIVE: To evaluate the effects of hypertonic, isooncotic, and isotonic infusion therapy on cerebral blood flow (CBF) during and after cardiopulmonary resuscitation (CPR) from experimental cardiac arrest (CA). METHODS: In 32 domestic swine (13-23 kg) open chest CPR was initiated after 8 min of ventricular fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min of either hypertonic saline (HS: 7.2% NaCl), hypertonic-isooncotic HES-saline (HHS: 7.2% NaCl in 6% HES 200,000/0.5), isooncotic HES (6% HES 200,000/0.5), or isotonic (normal) saline (NS: 0.9% NaCl). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure CBF quantitatively before CA, during CPR, and 20, 90 and 240 min after restoration of spontaneous circulation (ROSC). RESULTS: In HES/NaCl treated animals, CBF significantly decreased during CPR compared to the prearrest level (P < 0.01, respectively; MANOVA). In contrast, CBF was sustained during CPR in HS/HHS treated animals and significantly higher compared to animals receiving NS (P < 0.05, respectively). During recirculation severe postischaemic hypoperfusion as indicated by a decrease of CBF below the prearrest level, was present only in animals receiving HES and NS. CONCLUSIONS: Hypertonic solutions (HS/HHS) applied during internal cardiac massage enhanced CBF during CPR and after ROSC.

Animals↗

PubMed2004

Spectral entropy and bispectral index as measures of the electroencephalographic effects of sevoflurane.

BACKGROUND: Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors investigated the dose-response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS). METHODS: Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability. RESULTS: State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85 +/- 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE, respectively, and 0.80 +/- 0.06 for BIS. CONCLUSION: State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.

Adult↗

PubMed2003

Monitoring of cerebral perfusion pressure during intracranial hypertension: a sufficient parameter of adequate cerebral perfusion and oxygenation?

OBJECTIVE: A cerebral perfusion pressure (CPP) oriented treatment is a widely accepted standard for patients with intracranial hypertension. In an animal model of controlled intracranial hypertension we investigated whether CPP is a reliable parameter of sufficient cerebral perfusion and oxygenation. Using near-infrared reflexion spectroscopy the effect of decreasing CPP due to increasing intracranial pressure (ICP) on cerebral tissue oxygenation was studied. METHODS: Ten rabbits were subjected to artificially elevated ICP using the cisterna-magna infusion technique. Regional cerebral O(2) saturation of hemoglobin (tiSO(2)), regional tissue concentration of hemoglobin (tiHb), and CPP were recorded continuously. CPP was investigated with respect to tiSO(2). Electrocortical activity was simultaneously recorded by two-channel EEG to determine the onset of ischemia. RESULTS: Reduced CPP due to increased ICP led to a continuous decrease in tiSO(2.) There was progressive suppression of EEG frequency and amplitude with decreasing CPP in all animals. Onset of EEG-silence due to elevated ICP was observed in a wide range of CPP-values between 9 and 42 mmHg. At the same time tiSO(2) varied merely between 0 and 5%. CONCLUSIONS: Regarding the EEG effects due to increased ICP (EEG silence), CPP values showed a wide interindividual variability, in contrast to tiSO(2). In our animal model the sole calculation of CPP did not reflect adequate cerebral perfusion.

Animals↗

PubMed2003

A tumor necrosis factor gene polymorphism influences the inflammatory response after cardiac operation.

BACKGROUND: The genetic background may influence cytokine release evoked by cardiac operation. Thus we determined the allele frequency and genotype distribution of a bi-allelic tumor necrosis factor (TNF) gene polymorphism and TNF-alpha concentrations in patients undergoing cardiac operations with and without cardiopulmonary bypass (CPB). METHODS: The TNF NcoI gene polymorphism was identified by polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. Reading the size of the resulting DNA bands from the agarose gel defined the genotype as homozygous or heterozygous for the two alleles TNFB1 and TNFB2. Blood samples to determine TNF-alpha plasma levels were drawn from the patients before induction of general anesthesia after termination of CPB or after finishing coronary revascularization on the beating heart in non-CPB patients and 12 hours postoperatively. RESULTS: The genotype distribution and allele frequencies in 47 patients undergoing cardiac operation with CPB were comparable with those found in 36 patients undergoing cardiac operation without CPB. The TNF-alpha plasma levels over time were comparable in patients with and without CPB. However, patients homozygous for the TNF-B2 allele had significantly higher TNF-alpha plasma levels after termination of the CPB (40.2 +/- 3.5 pg/mL; mean +/- standard error of the mean; n = 28) compared with non-CPB patients (29.8 +/- 2.5 pg/mL; mean +/- standard error of the mean; n = 15) (p < 0.05). CONCLUSIONS: Patients homozygous for the TNF-B2 allele showed significantly higher TNF-alpha plasma levels after termination of CPB compared with non-CPB patients. Therefore preoperative TNF genotyping may be useful as patients with genetically determined increased proinflammatory cytokine expression with multiple comorbidities may in particular benefit from avoiding the use of CPB.

Adult↗

PubMed2003

Hypertonic saline improves myocardial blood flow during CPR, but is not enhanced further by the addition of hydroxy ethyl starch.

OBJECTIVE: To evaluate the effects of hypertonic saline (HS) and/or hydroxy ethyl starch (HES) on myocardial perfusion pressure (MPP) and blood flow (MBF), and cardiac index (CI) during and after cardiopulmonary resuscitation (CPR). METHODS: In 32 domestic swine (13-23.5 kg) open chest CPR was initiated after 8 min of ventricular fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min of either HS (7.2% NaCl) or hypertonic HES saline (HHS) (6% HES 200000/0.5 in 7.2% NaCl) or HES (6% HES 200000/0.5 in 0.9% NaCl) or normal saline (NS) (0.9% NaCl). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure MBF and CI before cardiac arrest, during CPR, and 20, 90 and 240 min after restoration of spontaneous circulation. RESULTS: During CPR HS and HHS significantly increased MBF in comparison to HES and NS (P<0.05, respectively, MANOVA). MPP and CI were not different between the groups. HS and HHS significantly increased resuscitation success and the 240 min survival rate. 14/15 animals receiving HS or HHS and 8/17 after HES-or NS -infusion survived the observation period (P<0.05, chi(2)-test). No negative side effects of HS with or without the addition of HES were observed. CONCLUSIONS: Hypertonic solutions (HS and HHS) applied during internal cardiac massage enhanced MBF and significantly increased resuscitation success and survival rate. Addition of HES to HS did not further improve the positive haemodynamic effects of HS alone.

Animals↗