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  • 1
    Electronic Resource
    Electronic Resource
    Einfluß eines intrakardialen Links-Rechts-Shunts auf pulmonal-arterielle Thermodilutionsmessungen des Herzzeitvolumens (1995)
    Springer
    Der Anaesthesist 44 (1995), S. 13-23 
    Details
    ISSN: 1432-055X
    Keywords: Schlüsselwörter: HZV-Messung – Pulmonaler Blutfluß– Thermodilutionsmethode – Intrakardialer Links-Rechts-Shunt ; Key words: Cardiac output measurement – Pulmonary blood flow – Thermodilution method – Intracardiac left-to-right shunt
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract. Thermodilution measurements of cardiac output (CO) by means of Swan-Ganz catheters, in a strict sense, represent pulmonary arterial blood flow (PBF). In principle, this is also true in the presence of intracardiac left-to-right shunts due to atrial or ventricular septal defects. However, early recirculation of indicator may give rise to serious methodological problems in these cases. We sought to determine the influence of intracardiac left-to-right shunts on different devices for thermodilution measurements of CO using an extracorporeal flow model. Methods. Blood flow was regulated by means of a centrifugal pump that at the same time enabled complete mixing of the indicator after injection (Fig. 1). Pulmonary and systemic parts of the circulation were simulated using two membrane oxygenators and a systemic-venous reservoir to delay systemic recirculation of indicator. Control measurements of PBF (Qp) and systemic (Qs) blood flow were performed by calibrated electromagnetic flow-meters (EMF). Blood temperature was kept constant using a heat exchanger without altering the indicator mass balance in the pulmonary circulation. Left-to-right shunt was varied at different systemic flow levels applying a Qp:Qs ratio ranging from 1:1 to 2.5:1. Thermodilution measurements of PBF were performed using two different thermodilution catheters that were connected to commercially available CO computers. Additionally, thermodilution curves were recorded on a microcomputer and analysed with custom-made software that enabled iterative regression analyses of the initial decay to determine that part of the downslope that best fits a monoexponentially declining function. Extrapolation of the thermodilution curve was then based on the respective curve segment in order to eliminate indicator recirculation due to shunt flow. Results. At moderate left-to-right shunts (Qp:Qs〈2:1) all thermodilution measurements showed close agreement with control measurements. At higher shunt flows (Qp:Qs≥2:1), however, conventional extrapolation procedures of CO computers considerably underestimated PBF (Fig. 2). This was particularly true when a slow-response thermistor catheter was used (Fig. 3). The reason for this underestimation of Qp was an overestimation of the area under curve because of inadequate mathematical elimination of indicator recirculation by standard truncation methods (Fig. 4). However, curve-alert messages of the commercially implemented software did not occur. A high level of agreement could be consistently obtained using a fast-response thermistor together with individual definition of extrapolation limits according to logarithmic regression analyses. Discussion and conclusion. Under varying levels of left-to-right shunt, both the reponse time of thermodilution catheters and the algorithms for calculation of flow considerably influenced the validity of thermodilution measurements of PBF in an extracorporeal flow model. The use of computer-based regression analyses to define the optimal segment for monoexponential extrapolation could effectively eliminate indicator recirculation from the initial portion of the declining thermodilution curve and showed the closest agreement with EMF measurements of Qp. The quality of thermodilution curves with respect to recirculation peaks in the flow model was slightly better than in clinical routine. Nevertheless, the clinical applicability of the modified extrapolation algorithm could be illustrated during pulmonary thermodilution measurements in an exemplary patient with a ventricular septal defect (Fig. 5). PBF at extremely high shunt ratios, however, cannot be assessed by monoexponential extrapolation in principle (Fig. 6). Insufficient elimination of indicator recirculation resulted in flow values that closely resembled systemic rather than PBF. This finding is in accordance with a mathematical analysis of the underlying Steward-Hamilton equation if an infinite number of recirculations would be included in the area under curve.
    Notes: Zusammenfassung. Thermodilutionsmessungen des HZV mittels pulmonal-arterieller Einschwemmkatheter repräsentieren im engeren Sinne den pulmonalen Blutfluß (Qp). Bei Vorliegen eines Vorhof- oder Ventrikelseptumdefekts können jedoch unphysiologisch frühe Rezirkulationen des injizierten Indikators zu methodischen Problemen führen. In der vorliegenden Untersuchung wurde daher in einem Kreislaufmodell der Einfluß eines Links-Rechts-Shunts auf 2 unterschiedliche HZV-Meßsysteme überprüft. Die Flußmessungen erfolgten bei 37 °C in zirkulierendem Blut unter Variation des Qp:Qs-Verhältnisses von 1:1 bis 2,5:1, eine Zentrifugalpumpe diente als Flußgenerator und als Mischkammer für den injizierten Indikator. Referenzmessungen des pulmonalen und des systemischen Stromzeitvolumens (Qs) wurden mittels elektromagnetischer Flowmeter durchgeführt. Hohe Shuntvolumina führten aufgrund einer mangelhaften Diskriminierung der Shunt-bedingten Kälterezirkulation zu einer erheblichen Unterschätzung des aktuellen Qp. Abweichungen von den Referenzflußmessungen fanden sich insbesondere bei einer vergleichsweise hohen Zeitkonstante des verwendeten Thermistors sowie bei Verwendung konventioneller Auswertungsalgorithmen, die eine monoexponentielle Extrapolation auf der Basis eines schematisch definierten Kurvenintervalls beinhalten. Die mangelnde Abgrenzung rezirkulierender Indikatoranteile führte zur Ermittlung eines Stromzeitvolumens, das an Stelle von Qp näherungsweise Qs repräsentierte. Eine bessere Übereinstimmung mit Qp-Referenzmessungen konnte durch ein dem Einzelfall angepaßtes Extrapolationsverfahren erzielt werden, das mittels Regressionsanalysen denjenigen Kurvenabschnitt ermittelt, der einem monoexponentiellen Abfall tatsächlich am nächsten kommt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001010050128
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  • 2
    Electronic Resource
    Electronic Resource
    HZV-Bestimmung mittels transpulmonaler Thermodilution Eine Alternative zum Pulmonaliskatheter? (1996)
    Springer
    Der Anaesthesist 45 (1996), S. 1045-1050 
    Details
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Herzzeitvolumen ; Thermodilution ; Säuglinge ; Kinder ; Erwachsene ; Key words Cardiac output ; Indicator dilution techniques ; Infants ; Children ; Adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Cardiac output measurements are often helpful in the management of critically ill patients and high risk-patients. In this study an alternative technique for measurement of cardiac output by the transpulmonary indicator dilution technique (TPID) was evaluated in comparison to conventional thermodilution using a pulmonary artery catheter. With TPID, a thermistor-tipped catheter (the smallest available is 1.3 F) is placed in the aorta via a femoral artery introducer. Thus, TPID can also be used in very small children in whom placement of a pulmonary artery catheter may be difficult or even impossible. In principle, TPID is less invasive since the possible complications of the pulmonary catheters are avoided. We investigated the accuracy and reproducibility of transpulmonary thermodilution in patients over a broad range in age and body surface. Methods. Following approval by the ethics committee and written consent, the data were obtained from 21 patients without a circulatory shunt undergoing diagnostic heart catheterization. The patients were between 0.5 and 25.2 years old, their body surface between 0.35 and 1.89 m2. Measurements were performed in duplicate with bolus injections of ice-cold normal saline (0.15 ml/kg), randomly spread over the respiratory cycle. In total 48 thermodilution curves were measured simultaneously in the pulmonary artery and in the aorta. Thermodilution curves were monoexponentially extrapolated for elimination of recirculation and cardiac output was calculated with a standard Stewart Hamilton procedure. Results. The amplitude of the typical arterial thermodilution curve shows a smaller and more delayed course than the pulmonary artery thermodilution curve. There was a very good correlation between the values found by pulmonary and TPID cardiac output measurements (R=0.968). There was a slightly smaller cardiac output value measured by the TPID (Bias=−4.7±1.5% sem) The reproducibility of duplicate measurements with the two methods were nearly the same, the standard deviation of the difference was 10.9% for the pulmonary thermodilution method and 11.7% for TPID. Discussion. TPID gives an alternative technique for measurement of cardiac output. We showed over a broad range in age and body surface a very good correlation with thermodilution measurements in the pulmonary artery. The slightly smaller values for TPID are explained by early recirculation, for clinical purposes the difference is negligible. However, the reproducibility of a method is clinically very important. Both methods showed in duplicate measurements basically the same reproduciblity. The disadvantage of TPID in being more sensitive to baseline alteration is counterbalanced by less respiratory variability in comparison to the conventional thermodilution technique. However, by increasing the amount of injected indicator (i.e., 0.2 ml/kg≅15 ml in an adult) it is possible to reduce the effect of baseline alteration. By using fiberoptic catheters it is even possible to use TPID as double-indicator dilution technique to measure intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). We conclude that in many patients TPID might be an attractive, less invasive and reliable alternative to conventional cardiac output measurement by pulmonary artery catheter.
    Notes: Zusammenfassung Die Messung des Herzzeitvolumens (HZV) ist zur Überwachung und Therapiesteuerung von Risikopatienten und Schwerstkranken häufig hilfreich. Die vorliegende Untersuchung beschreibt die HZV-Bestimmung mittels transpulmonaler Thermodilution (TPID) und vergleicht sie mit der herkömmlichen pulmonalarteriellen Thermodilution, wie sie unter Verwendung eines Pulmonaliskatheters klinisch breit angewendet wird. Bei sehr guter Übereinstimmung zwischen pulmonalarteriellem und transpulmonalem HZV (Bias=−4,7%±1,5% sem) über den gesamten untersuchten Altersbereich (0,5 bis 25,2 Jahre), besteht bei Doppelbestimmung auch eine vergleichbare Reproduzierbarkeit für die beiden Verfahren (SD=10.9% vs. 11,7%). Der geringeren Beeinflussung der HZV-Messung mittels TPID vom respiratorischen Zyklus steht die etwas größere Anfälligkeit gegenüber spontanen Temperaturschwankungen des Patienten entgegen. Im Gegensatz zur respiratorischen Abhängigkeit der pulmonalarteriellen Thermodilution kann die Anfälligkeit der TPID gegenüber diesen Temperaturschwankungen jedoch durch eine höhere Indikatordosierung weiter reduziert werden. Die zusätzlichen Einsatzmöglichkeiten in der pädiatrischen Anästhesie und Intensivmedizin, die prinzipiell geringere Invasivität und niedrigere Kosten sind Vorteile dieser Methode. Sie kann aber nicht bei allen klinischen Fragestellungen den Pulmonaliskatheter ersetzen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001010050338
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  • 3
    Electronic Resource
    Electronic Resource
    Messung der menschlichen Hirndurchblutung (1996)
    Springer
    Der Anaesthesist 45 (1996), S. 1030-1036 
    Details
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Kety-Schmidt-Technik ; 133Xe-Clearancetechnik ; Hirndurchblutung ; CO2-Reaktivität ; Key words Kety-Schmidt technique ; 133Xe-clearance technique ; Cerebral blood flow ; CO2-reactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract In this study cerebral blood flow (CBF) was simultaneously measured with the Kety-Schmidt method and the intravenous 133Xe clearance technique. CBF, cerebral metabolic rate of oxygen (CMRO2), and CO2 reactivity of CBF were compared under fentanyl-midazolam anaesthesia and varying paCO2 levels. Methods. Thirteen male patients were studied before they underwent coronary artery bypass surgery. For measurement of CBF with the Kety-Schmidt inert gas saturation technique, argon was used as indicator instead of nitrous oxide, because argon is less soluble in water and lipid such that arterial and hence organ saturation is attained earlier. Wash-in periods of 10 min were used for all measurements. For measurement of CBF with the intravenous xenon method 10 scintillation detectors placed lateral to the skull and an air detector for calculation of tracer recirculation were used. 10–15 mCi of 133Xe dissolved in physiological saline was injected via a peripheral i.v. cannula. For comparison with the Kety-Schmidt technique CBF15-values representing the flow of the grey and white matter were chosen. CBF was measured simultaneously with both methods under normocapnic (paCO2 43±3 mmHg), hypocapnic (paCO2 31±3 mmHg), and under hypercapnic (paCO2 54±4 mmHg) conditions. Results. All CBF15 values obtained with the intravenous xenon method were significantly lower than the corresponding CBF-values measured with the Kety-Schmidt technique: by 36% under normocapnic, 23% under hypocapnic, and 39% under hypercapnic conditions, respectively. Hence, CMRO2 values calculated from CBF values obtained with the xenon method were reduced to about the same degree as those derived from CBF values measured with the Kety-Schmidt technique. There was no significant correlation between the CBF values of either method (y=1.82x−8.58,r=0.76 P=0.357). Non-linear curve-fitting procedures yielded exponential CBF−paCO2 relationships for both methods, although the relative carbon dioxide reactivity was higher with the Kety-Schmidt technique than with the xenon method (y=8.14 e 0.039x vs y=10,75 e0.023 x ). Conclusions. Most probably due to contamination with radioactivity from slowly perfused extracerebral tissues the intravenous 133Xe-clearance technique underestimates CBF, CMRO2, and cerebrovascular CO2 reactivity, at least when CBF15 values are used as flow parameters.
    Notes: Zusammenfassung In der vorliegenden Untersuchung wurde die Hirndurchblutung simultan sowohl mit der intravenösen 133 Xenon-Clearancetechnik als auch mit der Kety-Schmidt-Technik gemessen. Unter Standardanästhesiebedingungen wurden Hirndurchblutung, zerebraler Stoffwechsel und die CO 2 -Reaktivität der Hirndurchblutung miteinander verglichen. Untersucht wurden 13 männliche Patienten, unmittelbar bevor sie sich einer aortokoronaren Bypassoperation unterzogen. Die Hirndurchblutungsmessungen wurden simultan durchgeführt und zwar jeweils unter normokapnischen (paCO 2 43±3 mm Hg), hypokapnischen (paCO 2 31±3 mm Hg) und hyperkapnischen (paCO 2 54±4 mm Hg) Bedingungen. Mit der Xenonmethode wurden unter allen Ventilationsbedingungen signifikant niedrigere Hirndurchblutungswerte gemessen als mit der Kety-Schmidt-Technik. Eine signifikante Korrelation zwischen den Hirndurchblutungswerten beider Methoden wurde nicht gefunden (y=1,82x−8,58, r=0,76, p=0,357). Die CO 2 -Antwortkurven der Hirndurchblutung zeigten für beide Verfahren einen exponentiellen Verlauf. Die CO 2 -Reaktivität war jedoch bei der Kety-Schmidt-Technik deutlichgrößer als bei der Xenonmethode (y=8,14e 0,039x vs. y=10,75 e 0,023x ). Wahrscheinlich aufgrund einer Miterfassung langsam perfundierter extrazerebraler Areale ist die intravenöse Xenonmethode unter Verwendung von CBF 15 als Durchblutungsparameter mit einer deutlichen Unterschätzung von Hirndurchblutung, -stoffwechsel und zerebrovaskulärer CO 2 -Reaktivität behaftet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001010050336
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  • 4
    Electronic Resource
    Electronic Resource
    Transpulmonale Indikatorverfahren in der Intensivmedizin (1998)
    Springer
    Der Anaesthesist 47 (1998), S. 220-228 
    Details
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Erweitertes hämodynamisches Monitoring ; Indikator ; Verdünnungstechnik ; Herzzeitvolumen ; Transpulmonale Thermodilution ; Transpulmonale Doppelindikatortechnik ; Intrathorakales Blutvolumen ; Extravaskuläres Lungenwasser ; Indozyaningrün ; Clearance ; Key words Advanced hemodynamic monitoring ; Indicator dilution technique ; Cardiac output ; Transpulmonary thermodilution ; Transpulmonary double indicator dilution ; Intrathoracic blood volume ; Extravascular lung water ; Indocyanine green-clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The management of critically ill patients often requires an advanced hemodynamic monitoring. Beside pulmonary artery catheter (PAC) and transesophageal echocardiography (TEE) the transpulmonary indicator dilution technique (TPID) with arterial registra-tion of the indicator dilution curves is a possi-ble approach to get additional hemodynamic information. Being less invasive, measurements of cardiac output by trans-pulmonary thermodilution are as reliable as the thermodilution using a PAC.Transpulmonary thermodilution can be used even in small children. In addition, intrathoracic blood volume (ITBV) and extravascular lung water (EVLW) can be estimated. ITBV seems to be a better surrogate of cardiac filling than central venous pressure and pulmonary capillary wedge pressure. EVLW can be of special value in the fluid-management of patients with systemic inflammatory response syndrom or acute respiratory failure. By using the dye indocyanine green (ICG) as a second indicator TPID can be performed as transpulmonary double indicator dilution technique. The resulting thermodilution and dye curves are measured with a combined fiberoptic-thermistor catheter. This allows the more accurate measurement of ITBV and EVLW and in addition the assessment of total circulating blood volume and ICG-clearance. ICG-clearance serves clinically as a rapidly reacting indirect measure of liver function. As with the other methods of advanced hemodynamic monitoring the data available at present do not show a positive effect on the incidence of organ failure and mortality by monitoring critically ill patients with TPID. Before applying an advanced hemodynamic monitoring it should be asked critically which parameter is needed for the therapy-management of the individual patient. Based on this a differenciated monitoring decision has to be made.
    Notes: Zusammenfassung Die mittels transpulmonaler Indikatortech- nik gewonnenen Meßwerte erlauben im Gegensatz zum PAK nicht die Berechnung des pulmonalen Gefäßwiderstands und des globalen Sauerstoffverbrauchs, die Messung des pulmonalarteriellen Drucks ist nicht möglich. Vorteile: Die transpulmonalen Indikatorverfahren ergeben jedoch gerade für kritisch kranke Intensivpatienten wertvolle Informationen. Die Thermodilutionsmessung des HZV ist transpulmonal weniger invasiv als die pulmonalarteriell unter Verwendung eines PAK registrierte. Auch können HZV-Messungen bei Kleinkindern (bis hinab zu einem Körpergewicht von etwa 3 kg) vorgenommen werden, für die bisher kein ausreichend zuverlässiges Verfahren zur Verfügung stand. Die bei bekanntem HZV zu berechnenden hämodynamischen Parameter Gefäßwiderstand, Schlagvolumen und globales Sauerstoffangebot sind Voraussetzung für eine rationale Therapie mit positiv inotropen und/oder vasoaktiven Substanzen. Eine individuell angepaßte, optimierte Volumentherapie wird bei den typischen Problempatienten der heutigen Intensivtherapie verstärkt gefordert. Dies gilt gleichermaßen für Patienten mit einer primären kardialen Problematik wie für Patienten mit einer schweren systemischen Entzündungsreaktion (SIRS) oder einem akuten Lungenversagen (ARDS). Die bisher vielfach vorgenommene indirekte Einschätzung der kardialen Füllung durch Messung des ZVD bzw. PCWP zeigt insbesondere bei der Erfassung längerfristiger Veränderungen erhebliche – methodisch und physiologisch zu begründende – Fehlermöglichkeiten. Das ebenfalls durch transpulmonale Thermodilution, genauer aber durch arterielle Farbstoffverdünnungskurven abzuschätzende ITBV ist ein besserer Parameter der kardialen Füllung. Insbesondere unter gleichzeitiger Beachtung des EVLW läßt sich die Volumengabe kritisch monitoren. Der häufig erforderliche Kompromiß zwischen einer ausreichenden regionalen Organperfusion und der Vermeidung eines pulmonalen und intestinalen Ödems ist fundierter möglich als mit bisher zur Verfügung stehenden diagnostischen Verfahren. Die zusätzlich aus der Farbstoffverdünnungskurve zu ermittelnde ICG-Clearance kann als Leberfunktionsparameter hilfreich sein. Ausblick: Entscheidend für die Beurteilung der Wertigkeit auch der transpulmonalen Indikatorverfahren wird es sein, inwieweit es gelingt, in prospektiven, größeren Studien letztlich einen Effekt auf die Inzidenz von Organversagen und Überlebensrate zu zeigen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001010050550
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  • 5
    Electronic Resource
    Electronic Resource
    Should we measure plasma volume in intensive care medicine? (1999)
    Springer
    Intensive care medicine 25 (1999), S. 1212-1214 
    Details
    ISSN: 1432-1238
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340051048
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  • 6
    Electronic Resource
    Electronic Resource
    Skin temperatures, thermosensory and pleasantness estimates in case of heterogeneity in the thermal environment
    Amsterdam : Elsevier
    Journal of Thermal Biology 18 (1993), S. 329-333 
    Details
    ISSN: 0306-4565
    Keywords: Skin temperature ; climate heterogeneity ; comfort ; thermal sensation
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0306-4565(93)90054-W
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  • 7
    Electronic Resource
    Electronic Resource
    The PstI polymorphism of the endotoxin-inducible heat-shock protein 70–2 gene does not affect messenger RNA level in human whole-blood cultures (2000)
    Springer
    Intensive care medicine 26 (2000), S. 1139-1143 
    Details
    ISSN: 1432-1238
    Keywords: Key words Inducible heat-shock-protein 70 ; PstI gene polymorphism ; Reverse transcription-polymerase chain reaction ; Endotoxin ; Heat-shock-protein 70 mRNA expression ; Clinical outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine whether the human leukocyte antigen linked biallelic heat-shock protein 70–2 (HSP70–2) gene polymorphism is associated with variable HSP70–2 messenger RNA expression. Design: Prospective observational study in consecutive healthy blood donors. Setting: Department of Anesthesiology, laboratory for molecular biology in a university hospital. Participants: 24 healthy blood donors. Interventions: None. Measurements and results: We studied the functional implication of the HSP70–2 (G/A) PstI gene polymorphism in 24 healthy, white blood donors with various HSP70–2 (G/A) genotypes by analyzing the endotoxin-inducible HSP70–2 mRNA expression by means of the reverse transcription–polymerase chain reaction. HSP70 expression was expressed semiquantitatively by calculating the ratio of HSP70–2 mRNA and the constitutively expressed glutaraldehyde 3-phosphate dehydrogenase mRNA. No significant differences in HSP70–2 mRNA expression after lipopolysaccharide (from Salmonella minnesota Re 595) stimulation were detected in individuals homozygous for the allele A (0.68, range 0.38–1, n = 10), in individuals homozygous for the allele G (0.79, range 0.42–1.1, n = 8), and in heterozygotes (HSP70–2 G/A; 0.52, range 0.4–0.67, n = 6; p 〉 0.05). Conclusions: The PstI polymorphism of the endotoxin-inducible HSP70–2 gene is not associated with variable HSP70–2 mRNA expression ex vivo. This finding is in accordance with the observation that HSP70–2 genotypes do not affect clinical outcome in human systemic inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340051329
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  • 8
    Electronic Resource
    Electronic Resource
    Endotoxin inhibits heat shock protein 70 (HSP70) expression in peripheral blood mononuclear cells of patients with severe sepsis (1999)
    Springer
    Intensive care medicine 25 (1999), S. 52-57 
    Details
    ISSN: 1432-1238
    Keywords: Key words Heat shock protein 70 ; Peripheral blood mononuclear cells ; HSP70 enzyme-linked immunosorbent assay ; Lipopolysaccharide ; Severe sepsis ; Stress protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To investigate the ex vivo endotoxin-inducible heat shock protein 70 (HSP70) expression in the peripheral blood mononuclear cells (PBMC) of patients with severe sepsis in order to assess the capacity of this potentially protective response during systemic inflammation. Design: Prospective observational study in consecutive patients with severe sepsis and healthy blood donors. Setting: Surgical intensive care unit in a university hospital. Patients and participants: Eleven patients with the diagnosis of severe sepsis, one patient who had recovered from severe sepsis and 13 healthy blood donors. Interventions: None. Measurements and results: We studied the inducibility of HSP70 expression in the PBMC of patients with severe sepsis and healthy blood donors ex vivo. Human whole blood was incubated with variable lipopolysaccharide (LPS from Salmonella minnesota Re 595) concentrations (0; 0.1; 10; 100 ng/ml) for different periods of time (0.5; 2; 4; 10 h). The PBMC were separated by Ficoll density gradient and then disrupted by hypotonic lysis. HSP70 was measured by means of enzyme-linked immunosorbent assay (ELISA). We found a LPS dose- and time-dependent inhibition of ex vivo HSP70 expression in the PBMC of both patients with severe sepsis and healthy individuals. However, the levels of HSP70 expression in patients were significantly lower compared to those of healthy individuals at all LPS concentrations and incubation times. On average, HSP70 expression in the PBMC of healthy controls was 2.8 (range 1.2–3.9) times higher than in patients. HSP70 expression was inducible by thermal heat shock in the PBMC of both patients and healthy individuals. Conclusions: Endotoxin inhibits HSP70 expression in PBMC ex vivo. In vivo, the suppression of HSP70 expression induced by endotoxin and high levels of proinflammatory cytokines may contribute to the cellular dysfunction of immunocompetent cells concerning antigen presentation, phagocytosis and antibody production associated with decreased resistance to infectious insults during severe sepsis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050786
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  • 9
    Electronic Resource
    Electronic Resource
    Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(S)-4-hydroxyphenylglycine] (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 327 (1984), S. 70-74 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac metabolism ; Myocardial ischemia ; Oxfenicine ; Oxygen debt ; Oxygen repayment ; Release of electrolytes and substrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Potential protective effects of oxfenicine [(S)-4-hydroxyphenylglycine] in ischemic stressed canine myocardium have been studied. This compound is characterized as a drug leading to metabolic inhibition of free fatty acid (FFA) metabolism. The drug (0.06 mmol·kg−1 body weight) caused no changes in hemodynamics or energy demand (Et) but depressed myocardial oxygen consumption (MVO2) by 11% (P〈0.02). Significant changes in FFA and lactate metabolism were observed: lactate extraction (EX) increased from 22.5–37.1 μmol/min, extraction ratio (EXR) from 16.5–30% and oxygen extraction ratio (OER) from 24.8–38%; EX of FFA decreased from 6900–5000 nmol/min, EXR from 48.2–31.4% and OER from 59.7–46.6%. Arterial concentrations of FFA and lactate remained unchanged. EX, EXR and OER of glucose were not affected under basic conditions. In the same collective, repeated ischemia (3 min) was produced by proximal occlusion of the left anterior descending artery (LAD). The efficiency of the drug was examined by (a) the amounts of ischemia metabolites released in the early reperfusion and (b) quantification of O2-debt and O2-repayment in the occlusion- and reperfusion periods. Compared to control occlusions, premedication led to a reduced O2-debt (P〈0.01) combined with a reduced amount of oxygen additionally taken up in the early reperfusion (P〈0.05). Furthermore, release of potassium increased (+7.1%; P〈0.05); release of lactate (-32%, P〈0.001) and inorganic phosphate (-34%, P〈0.01) decreased. These data give support to the concept that a pharmacologically induced shift of cardiac metabolism with reduction of FFA utilisation may be favourable in circumstances with limited oxygen supply.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00504994
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  • 10
    Electronic Resource
    Electronic Resource
    Effectiveness of nicorandil in the preservation of myocardium stressed by transient ischemia and its influence on cardiac metabolism during coronary artery occlusion with subsequent reperfusion: a comparison with isosorbide dinitrate (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 440-446 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac metabolism ; Ischemia ; Isosorbide dinitrate ; Nicorandil ; Oxygen-debt ; Oxygen-repayment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was designed to investigate the effects of nicorandil in comparison to isosorbide dinitrate (ISDN) on hemodynamics, on myocardial metabolism and on effectiveness in the preservation of ischemically stressed myocardium. Repeated ischemia (3 min) was produced in anaesthetized open-chest mongrel dogs by proximal, intermittent left anterior descending artery occlusion with subsequent reperfusion. In each experiment 2–3 control occlusions were compared to 2–3 occlusions under nicorandil or ISDN. Application of both nicorandil (0.64 μmol·kg−1 body weight, i.v.) and ISDN (1.27 μmol·kg−1 body weight, i.v.) led to a significant afterload reduction and to a decrease of the coronary vascular resistance. The efficiency of the compounds in the protection of ischemic myocardium was examined by quantification of oxygen-debt and oxygen-repayment in the occlusion and reperfusion periods. Compared to control, premedication with nicorandil led to a significant increase of oxygen-debt, whereas ISDN reduced it significantly. Oxygen-repayment remained unchanged. The influence of the drugs on the metabolism of glucose, lactate and free fatty acids (FFA) was examined under basic conditions, in ischemia and during reperfusion. For all substrates, extraction, extraction ratio and oxygen extraction ratio were calculated. Under basic conditions, glucose metabolism was significantly enhanced in both groups but FFA metabolism was inhibited only by ISDN. In ischemia, FFA metabolism was enhanced by nicorandil and depressed by ISDN. Data obtained in this study suggest that nicorandil may even aggravate the metabolic and energetic situation of ischemic myocardium and, on the other hand, clearly support the well documented protective effects of ISDN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00496379
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