Biomedical subjects

A Heller

Publications and source records attributed to A Heller.

At least 73 records · Page 4Linked to original sources

PubMed1999

Effects of endothelin-1 on bacterial clearance in rabbits.

As elevated endothelin-1 (ET-1) levels have been reported in systemic inflammatory diseases, the role of ET-1 as a promoter of inflammatory reactions is currently under investigation. The purpose of this study was to investigate the potential influence of ET-1 on systemic vascular pressure and immune function in terms of blood clearance and organ distribution of injected Escherichia coli in a rabbit model. To enable quantification of the clearance process, defined numbers of exogenous E. coli (10(8) cfu) were injected intravenously 60 min after starting the infusion of ET-1 (0.2 microgram kg-1 min-1; n = 9) or after saline infusion (controls, n = 9). Parameters monitored were arterial blood pressure, airway pressure, serum lactate concentrations and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were killed, and tissue samples of liver, kidney, spleen and lung were collected for bacterial counts. ET-1 infusion produced an increase in mean arterial pressure (83.9 +/- 3.9 mmHg vs. 50.1 +/- 4.1 mmHg at 120 min; P < 0.01) associated with higher serum lactate concentrations (12.6 +/- 1.3 vs. 5.4 +/- 0.3 mg dL-1; P < 0.001) and a delayed bacterial elimination from the blood compared with controls. Furthermore, there was increased colonization of the lungs (3.6 +/- 0.5 x 10(3) cfu vs. 745 +/- 120 cfu; P < 0.01), spleen (142.4 +/- 45.4 x 10(3) cfu vs. 227 +/- 5.2 x 10(3) cfu; P < 0.05) and kidney (758 +/- 329 vs. 357 +/- 151 cfu; NS), reflecting a reduced bacterial killing function.

Animals↗

PubMed1999

Ciprofloxacin concentrations in lung tissue following a single 400 mg intravenous dose.

Intravenous ciprofloxacin is frequently prescribed for the treatment of infections due to nosocomially acquired gram-negative organisms, including those originating in the respiratory tract. In this study, the concentrations of ciprofloxacin in serum and lung tissue were determined by HPLC in patients undergoing lung surgery. A total of 22 patients scheduled for lung surgery received a single 400 mg i.v. dose of ciprofloxacin administered as a 1 h infusion. A specimen of healthy lung tissue was obtained from resected lung from 18 of the patients for analysis of ciprofloxacin concentration during the following time intervals after infusion (one sample/patient): 0-2, 2-4, 4-8 and 8-12 h. Corresponding mean serum and tissue concentrations were 2.37 mg/L and 3.84 mg/kg (0-2 h), 1.18 mg/L and 1.92 mg/kg (2-4 h), 0.69 mg/L and 1.77 mg/kg (4-8 h), and 0.13 mg/L and 0.67 mg/kg (8-12 h). Ciprofloxacin distributed rapidly to lung tissue, as seen by the high concentrations in the lung tissue as early as 2 h after infusion. Concentrations in lung tissue were generally higher than those in serum (tissue:serum ratios ranged from 1.7 to 7.1). The mean tissue concentrations found in this study remained above the MIC for most susceptible organisms.

Adult↗

PubMed1999

Pancreatitis-associated protein protects the lung from leukocyte-induced injury.

BACKGROUND: Severe pancreatitis is often complicated by shock and acute lung failure. Little is known about the pathophysiologic impact of the 16.6-kD lectine, named pancreatitis-associated protein (PAP), which is expressed during pancreatitis and which reduces mortality in a rat model with severe pancreatitis. Therefore, the aim of this study was to investigate the effects of PAP on the pulmonary vasculature after leukocyte activation with N-formyl-Met-Leu-Phe (fMLP). METHODS: The experiments were performed in buffer-perfused isolated rabbit lungs. Mean pulmonary artery pressure, weight gain, and thromboxane A2 synthesis of the lungs were monitored. PAP was obtained by affinity chromatography of pancreas juice from pancreatitic rats. The authors tested whether treatment with PAP (260 microg/l, n = 9; or 500 microg/l, n = 6) before fMLP injection (10(-6) M) influences mean pulmonary artery pressure and edema formation. Lungs that were treated only with fMLP (n = 6) served as controls. Additional experiments in which PAP was applied were performed to study whether PAP (260 microg/l, n = 3; 500 microg/l, n = 3; 1,000 microg/l, n = 3) itself effects lung vasculature. RESULTS: Application of fMLP resulted in an increase of mean pulmonary artery pressure (+/- SD) from 8 +/- 2 mmHg up to 26 +/-13 mmHg (P < 0.01) at a flow of 150 ml/min. Pretreatment with PAP reduced the peak pressure developed after fMLP to 15 +/- 7 mmHg (PAP 260 microg/l; P < 0.05) and to 9 +/- 4 mmHg (PAP 500 microg/l), respectively. In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration. In parallel to the attenuated pressure increase, thromboxane A2 release was significantly suppressed in the 260-microg/l (200 +/- 220 pmol x ml(-1) x min(-1); P < 0.01) and 500-microg/l (285 +/- 70 pmol x m(-1) x min(-1); P < 0.05) PAP groups compared with controls (1,138 +/- 800 pmol x ml(-1) x mi(-1)). Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release. CONCLUSION: Clinically relevant concentrations of PAP prevented fMLP-induced vasoconstriction and edema formation in the lung. These findings point toward a protective effect of PAP on polymorphonuclear neutrophil leukocyte-mediated lung injury.

Acute-Phase Proteins↗

PubMed1999

Pentoxifylline improves bacterial clearance during hemorrhage and endotoxemia.

OBJECTIVE: The aim of this study was to investigate whether the methylxanthine-derivative pentoxifylline (PTX) affects bacterial clearance of the organism in states of hemorrhage and endotoxemia. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Fifty-four female chinchilla rabbits. INTERVENTIONS: To quantify the clearance process, defined numbers (10(7) CFO) of Escherichia coli bacteria were injected intravenously into anesthetized rabbits, 60 mins after induction of hemorrhage (n = 9 + 3) or infusion of endotoxin (lipopolysaccharide [LPS]; 40 microg/kg/hr; n = 9 + 3) and after saline infusion (control; n = 9), respectively. Hemorrhage was induced by bleeding, standardized by defined reduction of mean arterial pressure (30% of baseline value). To evaluate the potential effects of PTX on bacterial elimination and killing, in states of hemorrhage and endotoxemia, blood clearance of E. coli and colonization of different organs were investigated after pretreatment with PTX (30 mg/kg) as a bolus injection followed by continuous infusion of PTX (50 mg/kg/hr) in hemorrhagic (n = 9) and endotoxemic rabbits (n = 9). Three additional experiments were performed to evaluate the effects attributable to PTX itself. MEASUREMENTS AND MAIN RESULTS: Parameters monitored were rates of bacterial and LPS elimination from the blood, arterial blood pressure, blood gases, and serum lactate concentrations. Additionally, flow cytometric analysis of respiratory burst activity was performed. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, kidney, spleen, and lung were collected for bacteriologic examinations. Compared with the controls, hemorrhage and endotoxemia resulted in a significantly prolonged elimination of injected E. coli from the blood. The delayed blood clearance was associated with a significantly (p < .01) higher bacterial colonization of all organs, which was most pronounced in the lung. Pretreatment with PTX slightly enhanced blood clearance of E. coli as well as of LPS, and significantly reduced (p < .05) the colonization of lung and kidney after hemorrhage and endotoxemia. Furthermore, PTX suppressed polymorphonuclear neutrophil respiratory burst activity. CONCLUSIONS: Hemorrhage and endotoxemia induce impaired bacterial clearance from blood and tissue. Treatment with PTX may reduce the risk of bacterial infections by attenuating bacterial colonization of organs in states of hemorrhage and endotoxemia.

Animals↗

PubMed1999

Characterization and distribution of endothelin receptors in the pulmonary circulation: investigation of isolated, perfused, and ventilated rabbit lungs.

The aim of the study was to investigate the distribution of 2 subtypes of endothelin-receptors, mediating the effects of endothelin-1 (ET-1) in the pulmonary circulation. Until now, it is still unclear, whether ET(A) receptors or ET(B) receptors or even both are localized in pulmonary vessels. The experiments were performed on 72 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. The arterial pressure and the lung weight gain were continuously registered. Intermittently perfusate samples were taken for determination of thromboxane A2 (TXA2) and prostacyclin (PGI2). The injection of ET-1 (10(-8) M, n = 6) resulted in a biphasic increase in pulmonary arterial pressure (PAP) that was accompanied by the generation of TXA2 and PGI2. Pretreatment with the ET(A)-receptor antagonist LU135252 (10(-6) M, n = 6) suppressed the pressure response after ET-1 application (P < 0.01 at 120 min) and reduced the generation of TXA2 (P < 0.05 at 120 min) and PGI2 (P < 0.05 at 120 min). Pretreatment with the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6) also reduced the PAP increase after ET-1 injection. In contrast to this, the pulmonary vascular pressure reaction after ET-1 application was elevated, when ET(B)-receptor antagonist BQ788 (10(-6) M; n = 6) was given. Furthermore, the PGI2 to TXA2 ratio was shifted from 2.3 to 0.9, reflecting a predominance of vasoconstrictive TXA2. The simultaneous application of LU135252 and BQ788 significantly reduced the PAP increase after ET-1 application, but no beneficial effects were observed compared with the application of LU135252 solely. The injection of the ET(B)-receptor agonist sarafotoxin S6c (S6c; 10(-8) M, n = 6) also induced an increase in PAP that was not attenuated by pretreatment with the ET(B)-receptor antagonist BQ788 (10(-6) M, n = 6). LU135252 (n = 6) as well as the application of LU135252 in combination with BQ788 (n = 6) failed to suppress the pressure response after S6c, whereas the cyclooxygenase inhibitor diclofenac (10 microg/mL, n = 6) alone and in combination with LU135252 and BQ788 (n = 6) was able to prevent the PAP increase after S6c injection (P < 0.001). The results demonstrate that the ET-1-induced increase in pulmonary vascular resistance is mainly mediated via ET(A) receptors, whereas ET(B) receptors seem to mediate vasodilation, which was shown by an imbalance of TXA2 and PGI2 generation. On the other hand, the ET(B)-receptor agonist S6c induced vasoconstriction, which was only attenuated by the cyclooxygenase inhibitor diclofenac. From the current results we conclude that, apart from vasoconstrictor ET(A) receptors, at least 2 ET(B)-receptor subtypes are expressed in the pulmonary circulation, one mediating vasoconstriction, which was not blocked by BQ788, and one mediating vasodilation, which was influenced by BQ788.

Animals↗

PubMed1999

Implanted electrochemical glucose sensors for the management of diabetes.

By maintaining a near normal (70-120 mg/dL) glucose concentration, diabetic patients can drastically reduce the likelihood of the occurrence of diabetes complications. In the near future, subcutaneously implanted electrochemical glucose sensors will be available to provide frequent or continuous information on which timely treatment decisions, such as insulin injection or glucose source intake, can be based, as well as timely alarm signals. The currently engineered devices are of three types: (a) innocuous microsensors, with actively mass-transporting areas < 10(-3) cm2, replaced twice a week by the patient; (b) self-contained, surgeon-implanted, transmitter-containing packages of > 1 cm2 area, operating for > 100 days; and (c) devices transporting subcutaneous fluid to an external sensor, based on implanted microfiltration or microdialysis fibers or on iontophoretic transport of the subcutaneous fluid through the skin.

Biocompatible Materials↗

PubMed1999

Molecular cytogenetic characterization of a prenatally detected supernumerary minute marker chromosome 8.

The characterization of a prenatally detected very small (approximately half of 18p-(karyotype: 47,XX,+mar[16]/46,XX[7]) supernumerary marker chromosome (SMC) identified by GTG-banding analysis is described. The marker has been identified as derived from chromosome 8 centromeric material using a combination of different cytogenetic (GTG-, NOR-, CBG banding), molecular cytogenetic (24 colour-fluorescent in situ hybridization [FISH], three-colour FISH using centromeric probes for all human chromosomes) and molecular genetic techniques (microsatellite analysis). This is the first case described with such a minute SMC derived from chromosome 8 diagnosed prenatally, the 15th case reporting on a SMC originating from chromosome 8 and the third such case without any severe clinical features.

Adult↗

PubMed1998

Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee with a miniature subcutaneous electrode.

The performance of an amperometric biosensor, consisting of a subcutaneously implanted miniature (0.29 mm diameter, 5 x 10(-4) cm2 mass transporting area), 90 s 10-90% rise/decay time glucose electrode, and an on-the-skin electrocardiogram Ag/AgCl electrode was tested in an unconstrained, naturally diabetic, brittle, type I, insulin-dependent chimpanzee. The chimpanzee was trained to wear on her wrist a small electronic package and to present her heel for capillary blood samples. In five sets of measurements, averaging 5 h each, 82 capillary blood samples were assayed, their concentrations ranging from 35 to 400 mg/dl. The current readings were translated to blood glucose concentration by assaying, at t = 1 h, one blood sample for each implanted sensor. The rms error in the correlation between the sensor-measured glucose concentration and that in capillary blood was 17.2%, 4.9% above the intrinsic 12.3% rms error of the Accu-Chek II reference, through which the illness of the chimpanzee was routinely managed. Linear regression analysis of the data points taken at t>1 h yielded the relationship (Accu-Chek) = 0. 98 x (implanted sensor) + 4.2 mg/dl, r2 = 0.94. The capillary blood and the subcutaneous glucose concentrations were statistically indistinguishable when the rate of change was less than 1 mg/(dl. min). However, when the rate of decline exceeded 1.8 mg/(dl.min) after insulin injection, the subcutaneous glucose concentration was transiently higher.

Animals↗

PubMed1998

Accuracy of the one-point in vivo calibration of "wired" glucose oxidase electrodes implanted in jugular veins of rats in periods of rapid rise and decline of the glucose concentration.

The hypothesis of the feasibility of one-point in vivo calibration of intravenously implanted glucose sensors during periods of rapid rise and decline of venous blood glucose concentration was tested. Miniature (5 x 10(-4) cm2 mass transporting area) glucose electrodes with 10-90% response times < 2 min, that did not consume oxygen, were implanted in jugular veins of systemically heparinized rats and used in 4-h experiments, during which the blood glucose concentration was amperometrically monitored. The glucose electrodes were made by electrically connecting ("wiring") reaction centers of glucose oxidase through an electron-conducting redox hydrogel to gold electrode surfaces. The redox polymer and enzyme constituting the electrode sensing layer were immobilized by cross-linking, and thus the electrodes had no diffusional and readily leached redox mediator. One hour after their implantation, the electrodes accurately tracked the blood glucose concentration when calibrated in vivo by a one-point calibration, when the glucose concentration was steady, when rising rapidly, and when declining steeply. For an assumed 2-min lag time, the sensor readings were well correlated with the true blood glucose concentrations, with linear regression analysis yielding a slope of 0.97 +/- 0.07 and an intercept (bias) of 0.3 +/- 0.3 mM. The correlation coefficient, r2, was 0.949 +/- 0.020, and the percent difference through the 2-22 mM range was 1.9 +/- 1.0%. The results suggest that, in combination with understanding and modeling of transient physiological differences between the subcutaneous and the blood glucose concentrations, it will be possible to calibrate by one-point in vivo calibration subcutaneously implanted sensors, even while the glucose concentration changes rapidly.

Animals↗

PubMed1998

Measurement and modeling of the transient difference between blood and subcutaneous glucose concentrations in the rat after injection of insulin.

The kinetics of the fall in subcutaneous fluid glucose concentration in anesthetized rats (n = 7) after intravenous injection of insulin (0.5 units/kg) was studied by using 5 x 10(-4) cm2 active area, <150-sec 10-90% response time, amperometric glucose sensors. The onset of the decline in the subcutaneous glucose concentration was delayed and statistically different (P < 0.001) from that in blood (8.9 +/- 2.1 min vs. 3.3 +/- 0.5 min). Similarly, the rate of drop in glucose concentration between 6 and 20 min after the insulin injection was different for subcutaneous tissue (3.9 +/- 1.3 mg.dl-1. min-1) and blood (6.8 +/- 2.0 mg.dl-1.min-1) (P = 0.003). The hypoglycemic nadir in subcutaneous fluid occurred 24.5 +/- 6.8 min after that in the blood (P < 0.001). A "forward" mass-transfer model, predicting the subcutaneous glucose concentration from the blood glucose concentrations and an "inverse" model, predicting the blood glucose concentration from the subcutaneous glucose concentration were derived. By using an algorithm based on the latter, the average discrepancy between the measured blood glucose concentration and that estimated from the subcutaneous measurement through the entire 4-hr experiment was reduced from 22.9% to 11.1% (P = 0.025). The maximum discrepancy during the 40-min period after the injection of insulin was reduced from 84.1% to 29.3% (P = 0.006).

Algorithms↗

PubMed1998

The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs.

OBJECTIVE: It is well known that lung embolism is associated with an increase in pulmonary vascular resistance. Since the mechanisms of pulmonary vascular reactions during embolism are still unclear, the aim of this study was to investigate the potential involvement of endothelin-1 (ET-1) and thromboxane A2 (TXA2) as mediators of the pulmonary artery pressure (PAP) increase after embolism using the selective ETA receptor antagonist LU135252 [1], the ETB receptor antagonist BQ788 [2], and the cyclooxygenase inhibitor diclofenac. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: 36 adult rabbits of either sex. INTERVENTIONS: The experiments were performed in 36 isolated and ventilated rabbit lungs which were perfused with a buffer solution containing 10% of autologous blood. Embolism was induced by the injection of 0.75 ml air into the pulmonary artery. MEASUREMENTS AND RESULTS: PAP and lung weight, reflecting edema formation, were continuously recorded. Perfusate samples were drawn intermittently to determine TXA2 and ET-1 concentrations. Air injection resulted in an immediate increase in PAP up to 22.8 +/- 1.4 mm Hg at 2.5 min (control, n = 6), which was parallelled by an enhanced generation of TXA2. No relevant edema formation occurred during the observation period. Pretreatment with the ETA receptor antagonist LU135252 significantly reduced the pressure reaction after air embolism (p < 0.001) whereas the ETB receptor antagonist BQ788 (n = 6) was without marked effects. The administration of diclofenac (n = 6) did not alter the PAP increase 2.5 min after embolism, but significantly reduced the pressure reaction during the further observation period (p < 0.001). The application of LU135252 and diclofenac together (n = 6) also significantly reduced the PAP increase from 2.5 min during the total observation period (p < 0.001). CONCLUSIONS: The acute pressure reaction after air embolism is mainly mediated via ET-1 by an ETA receptor related mechanism. TXA2 seems to maintain this reaction for a longer time.

Analysis of Variance↗

PubMed1998

Altered responses to potassium in cerebellar neurons from weaver heterozygote mice.

The pleiotropic weaver disease is caused by the mutation of a single amino acid in the G-protein-linked inwardly rectifying K+ channel, GIRK2. In homozygous (wv/wv) animals, the disease is characterized by loss of cerebellar and dopaminergic mesencephalic neurons as well as testicular cells, which produce ataxia, fine tremors, and sterility, respectively. Heterozygous (wv/+) animals show no obvious motor impairments, although some loss of both cerebellar and dopaminergic neurons is observed and wv/+ males become sterile at 3.5 months of age. Abnormal influxes of Na+ and Ca2+ have been linked to cerebellar cell death in wv/wv animals, but it's not clear whether similar changes are observed in wv/+ animals. To discover whether changes in K+-channel function or intracellular Ca2+ concentrations ([Ca2+]i) play a role in the augmented cell loss observed in wv/+ animals when compared with +/+ animals, we studied cultured cerebellar granule cells prepared from either wv/+ or +/+ animals. Resting [Ca2+]i was elevated in wv/+ relative to +/+ animals. Further, depolarizations of cells with elevated K+ solutions elicited much smaller changes in [Ca2+]i in wv/+ animals than in +/+ animals, presumably due to altered GIRK2 channel function. Both wv/+ and +/+ cells showed similar changes in [Ca2+]i when cells were depolarized by glutamate (1 mM), suggesting that both glutamate receptors and Ca2+ channels were unchanged in wv/ + animals. In summary, our results suggest that wv/+ cerebellar granule cells exhibit elevated resting [Ca2+]i levels and altered K+-channel function, which may contribute to the developmental abnormalities and increased cell death observed.

Animals↗

PubMed1998

No premature gene expression in germ cells of embryos deriving from nos females.

The product of nos is required at the posterior pole of the embryo for the differentiation of abdominal structures, but not for pole cell formation. A previous analysis that reported the expression of germline-specific enhancer-trap lines suggested that nos also controls the timing of the initiation of transcription of germline-specific genes. Here we repeat the experiments that led to this hypothesis and we report further experiments. Our results show that, contrary to what had been reported, germ cells of embryos deriving from nos females do not show premature gene expression. Germ cells of such embryos, however, often show artefactual lacZ staining even in the absence of a lacZ gene.

Animals↗

PubMed1998

In Drosophila, female gonadal cells repress male-specific gene expression in XX germ cells.

In Drosophila, the sex of XX germ cells is determined by somatic signals. Whether sex-specific genes, however, are activated or repressed by somatic signals is not known. We have used mgm1, a germline-marker which is specifically expressed in male germ cells to analyze sex-specific gene expression of embryonic germ cells. We found that XX and XY germ cells that do not contact gonadal tissue can express mgm1. In contrast, XX germ cells that were associated with female somatic gonadal cells never expressed mgm1. Our results suggest that XX germ cells express male-specific genes, unless these genes are repressed by feminizing short range signals produced by the somatic cells of the prospective ovary.

Animals↗

PubMed1998

[Pharmacologic aspects of polyunsaturated fatty acids in parenteral nutrition].

Despite immense progress in intensive-care medicine, mortality rates of 30-70% in sepsis and SIRS are still an unresolved problem. Particularly the failure of respiratory and other vital functions is a major cause of death. Besides infectious stimuli (viruses, bacteria, fungi) a variety of non-infectious triggers (tissue damage, immune complexes, complement activation, etc.) can initiate the development of organ failure. These inflammatory reactions aim physiologically towards inactivation and removal of the stimulating agents as well as the induction of reparative processes. In states of prolonged activation of humoral and cellular mediator systems the natural host defence mechanisms react in an uncontrolled manner causing tissue damage and organ failure. So far there are no efficient therapeutic strategies to influence these complex inflammatory reactions. In the development of SIRS and sepsis, pro-inflammatory lipid mediators play a crucial role. Omega-3-fatty acids (omega-3-PUFAs) have shown anti-inflammatory and antithrombotic properties in a great number of experimental and clinical studies. These effects seem to be related to the uptake of eicosapentaenoic acid (EPA) into cellular membrane lipid pools and its subsequent metabolisation. After inflammatory activation EPA is released besides arachidonic acid (AA) and competes with AA for metabolisation via the cyclo- and lipoxygenase pathway. Compared to AA the derivatives of EPA have less pro-inflammatory and chemotactic characteristics. With regard to prophylactic and therapeutic consequences it appears reasonable to supplement omega-3-PUFAs to attenuate the inflammatory response by modulating the generation of lipid mediators during inflammation.

Animals↗

PubMed1998

Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction.

UNLABELLED: The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured. RESULTS: In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP. CONCLUSION: The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.

Animals↗

PubMed1998

Effects of intravenous anesthetics on bacterial elimination in human blood in vitro.

BACKGROUND: Since anesthetics are widely used in critically ill patients, this study investigates anesthetic effects on neutrophil and monocyte function concerning bacterial elimination in human whole blood. METHODS: The effects of thiopental (20 and 200 microg/ml), propofol (5 and 50 microg/ml), midazolam (0.15 and 1.5 microg/ml) and ketamine (3 and 30 microg/ml) on elimination of Escherichia (E.) coli from whole blood were investigated in vitro after incubation for 1 h in both clinical (1) (n=10) and 10-fold higher (h) (n=11) concentrations. These data were compared to neutrophil and monocyte phagocytosis (1; n=6) and burst activity (1; n=10, h; n=11), measured by flow cytometry. To enable quantification of the clearance process, a defined number of 10(5) colony forming units of E. coli were added to the blood assays and bacterial growth was determined. RESULTS: All anesthetics delayed bacterial clearance from the blood in the 10-fold concentration (P<0.05). Thiopental (1+h) and propofol (h) suppressed neutrophil (59+/-3% and 38+/-6%) and monocytic (45+/-6% and 30+/-11%) oxidative burst (P<0.01). Phagocytosis was reduced even after propofol (1) in polymorphonuclear leukocytes (PMN) (34+/-9%; P<0.05) and monocytes (35+/-11%). Ketamine (h) prolonged bacterial elimination (P<0.01), which did correlate with inhibition of monocytic phagocytosis, by 26+/-14%. Midazolam application (h) resulted in an inhibition of PMN-respiratory burst by 19+/-6% (P<0.05) and impaired bacterial clearance (P<0.05). CONCLUSION: Thiopental, propofol, midazolam and ketamine affect E. coli clearance and neutrophil and monocyte oxidative burst and phagocytosis in vitro only in high concentrations, while thiopental inhibited monocytic burst and propofol impaired PMN phagocytosis even in clinically used concentrations. These data suggest that i.v. anesthetics in concentrations recommended for general anesthesia seem to have minor influence on the investigated host defense mechanisms.

Adult↗

PubMed1998

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans.

BACKGROUND: Ketamine in sub-dissociative doses has been shown to have analgesic effects in various pain conditions, including neuropathic and phantom-limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood. METHODS: Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS). RESULTS: Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all the patients at the highest dose (0.45 mg/kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. These 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/kg ketamine doses than for morphine 10 mg. CONCLUSION: We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.

Aged↗