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Zahlreiche In-vitro- und In-vivo-Studien belegen, dass Dopamin neben seinen hamodynamischen Effekten eine Reihe immunmodulatorischer Wirkungen induziert. Dopamin reduziert die Synthese proinflammatorischer und induziert die Synthese antiinflammatorischer Mediatoren. Dopamin hemmt die Synthese neurohypophysarer Hormone und hemmt die Zellproliferation sowie die Thrombozytenaggregation. Es reduziert die Phagozytoseaktivitat neutrophiler Granulozyten und induziert Apoptose. Bei hohen Dopaminserumkonzentrationen, wie sie bei einer Sepsis durch vermehrte endogene Synthese, zusatzliche exogene Applikation und verringerte Clearance erreicht werden, konnten diese Effekte zu relevanten Veranderungen pathophysiologischer Ablaufe fuhren. Um die Bedeutung von Dopamin fur die zellulare und humorale Immunantwort von Patienten mit Sepsis hervorzuheben, sind in dieser Ubersicht die speziellen Wirkungen von Dopamin zusammengefasst und die zugrunde liegenden Mechanismen dargestellt.

Ziel unserer Studie war, mit der Nah-Infrarot-Spektroskopie (NIRS) den Einfluss der zerebralen Oxygenierung (regionale zerebrale Sauerstoffsattigung rSO2) und mit der Pulsoxymetrie den Einfluss der nachtlichen Sauerstoffsattigung (SatO2) auf die postoperative Restitution kognitiver Funktionen bei Patienten zwischen 40 und 85 Jahren, die sich der elektiven Implantation einer Huft-Totalendoprothese unterzogen, zu bestimmen. Es wurden 40 Patienten (ASA II) randomisiert entweder in Allgemeinanasthesie oder in ruckenmarknaher Regionalanasthesie operiert. Die Patienten wurden in 2 Altersgruppen eingeteilt (40–64 Jahre und 65–85 Jahre). Neuropsychologische Tests wurden 14–16 h praoperativ (t0), 1,5 h postoperativ (t1), am 1. und 3. postoperativen Tag (t2 bzw. t3) durchgefuhrt. Die rSO2 wurde wahrend dieser Testungen sowie intraoperativ und bis 1,5 h postoperativ jeweils kontinuierlich abgeleitet. Die SatO2 wurde in der praoperativen (N0) sowie in der 1.–3. postoperativen Nacht (N1, N2, N3) uber einen Zeitraum von 7 h (22.00–05.00 Uhr) gemessen und in Intervallbereiche (80–83%, 84–87%, 88–91%, 92–95%, 96–100%) eingeteilt. Bei beiden Anasthesieverfahren und in beiden Altersgruppen kam es 1,5 h postoperativ (t1) zu einer Beeintrachtigung der kognitiven Leistungsfahigkeit. Diese Defizite bildeten sich in allen Gruppen bis zum 3. postoperativen Tag (t3) auf das praoperative Ausgangsniveau (t0) zuruck. Die rSO2 hingegen fiel bis t3 in allen Gruppen signifikant bis 3% unter den praoperativen Ausgangswert ab. Der prozentuale Anteil der Intervallbereiche an der Gesamtmesszeit der SatO2 verschob sich nach beiden Anasthesieverfahren und in beiden Altersgruppen von 96–100% in der praoperativen Nacht (N0) zum Intervall von 88–91% in der 2. postoperativen Nacht (N2). Zwischen der rSO2, der postoperativen kognitiven Leistungsfahigkeit und der SatO2 konnte in keiner Gruppe ein Zusammenhang nachgewiesen werden. Bei Patienten zwischen 40 und 85 Jahren (ASA II), die sich der elektiven Implantation einer Hufttotalendoprothese in Allgemein- oder ruckenmarknaher Regionalanasthesie unterziehen, erfolgt eine vollstandige Restitution der kognitiven Funktionen bis zum 3. postoperativen Tag trotz einer erniedrigten zerebralen Oxygenierung (rSO2) und trotz einer Zunahme von nachtlichen hypoxamischen Phasen. Veranderungen der rSO2, die mit der NIRS gemessen werden, ermoglichen keine prognostische Aussage zum Verlauf der kognitiven Leistungsfahigkeit. Die kognitive Restitution erfolgt innerhalb eines Bereiches bis 3% unter den Ausgangswert unabhangig vom jeweiligen rSO2-Wert. Ein unterer Grenzwert der rSO2 konnte in unserer Untersuchung nicht definiert werden.

1. In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A(2) (sPLA(2)) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA(2) in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA(2) inhibitors, specifically, the extracellular PLA(2) inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA(2). 2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-alpha and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-kappaB by LPS but not its activation by TNF-alpha or IL-1. 3. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA(2) activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA(2). It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA(2) inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA(2) inhibitor LY311727. 4. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation.

We addressed the question to which extent cerebral blood flow (CBF) is maintained when, in addition to a high blood viscosity (Bvis) arterial oxygen content (CaO2 ) is gradually decreased. CaO2 was decreased by hemodilution to hematocrits (Hct) of 30, 22, 19, and 15% in two groups. One group received blood replacement (BR) only and served as the control. The second group received an additional high viscosity solution of polyvinylpyrrolidone (BR/PVP). Bvis was reduced in the BR group and was doubled in the BR/PVP. Despite different Bvis, CBF did not differ between BR and BR/PVP rats at Hct values of 30 and 22%, indicating a complete vascular compensation of the increased Bvis at decreased CaO2 . At an Hct of 19%, local cerebral blood flow (LCBF) in some brain structures was lower in BR/PVP rats than in BR rats. At the lowest Hct of 15%, LCBF of 15 brain structures and mean CBF were reduced in BR/PVP. The resulting decrease in cerebral oxygen delivery in the BR/PVP group indicates a global loss of vascular compensation. We concluded that vasodilating mechanisms compensated for Bvis increases thereby maintaining constant cerebral oxygen delivery. Compensatory mechanisms were exhausted at a Hct of 19% and lower as indicated by the reduction of CBF and cerebral oxygen delivery.

Quality of care and costs are getting closer together. Whereas costs and quality management did not play a substantial role 30 years ago, the consumption of resources nowadays is part of the outcome of quality of care. The definition of quality must be seen in the dimensions of structure, process and result. Resulting from newly developed clinical practice, guidelines are planned as instruments for cost containment in near future. Those guidelines may end up in a quality management system. The most wellknown european basic of such a quality management system are the DIN EN ISO 9000 f and the EFQM. The ISO 9001 and the European Quality Award became the most common base of evaluation for certification of quality management systems in Organisations European wide. Whereas the ISO 9001 does not give any information about the real achieved quality, the European Quality Award reflects the process. Guidelines are necessary to prove the cost effectiveness of measures of quality control and quality assurance since too much quality control and assurance may result in increased overall consumption of resources, leading to a reduction in the quality of care when ensuring that the overall budget is covered.

Fragestellung: Ziel unserer Untersuchung war es, mogliche kognitive Funktionsdefizite geriatrischer Patienten nach Allgemein- und ruckenmarknaher Regionalanasthesie mit Parametern des Gasaustauschs (Sauerstoffpartialdruck paO2, Sauerstoffsattigung SatO2) und der Hamodynamik (arterieller systolischer und mittlerer Blutdruck RRs und MAP) in Beziehung zu setzen.

Background: The purpose of the study was to investigate the potential influence of the anaesthetic agent propofol on immune function in terms of systemic clearance and organ distribution of injected Escherichia coli in a rabbit model. Methods: Defined numbers of E. coli (1.3×108 colony-forming units, CFU) were injected intravenously 1 h after starting a 4-h infusion of the anaesthetic propofol (2 ml · kg−1 · h−1, Disoprivan® 1%; n=6)) or after saline application (n=6). As propofol is formulated in a 10% lipid emulsion, the lipid vehicle Intralipid® (2 ml · kg−1 · h−1; n=6) alone was investigated in a separate group. Parameters monitored were arterial pressure and rates of bacterial elimination from the blood. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, spleen, lung, and kidney were collected for microbiological examinations. Results: Compared to saline-treated animals, infusion of propofol induced increased accumulation of E. coli in lung and spleen, thus reflecting reticuloendothelial system dysfunction. Conclusion: As the lipid emulsion by itself induced the same effects, the impaired immune function due to propofol is thought to be attributed to its solvent Intralipid®.

Objective To test the hypothesis that the specific acute-phase response program of the pancreas is a powerful emergency defense mechanism that is beneficial during acute pancreatitis. Design Prospective, randomized, controlled animal study. Setting Research laboratory in a university medical school. Subjects Female Wistar rats, weighing 250 to 300 g. Interventions An acute-phase response was induced in rats subjected to hyperstimulation with cerulein. The development of the acute-phase reaction was monitored by the expression of the pancreatitis-associated protein I. In control animals, no acute-phase response was induced. After the first experimental procedure at periods of 2, 48, or 168 hrs, the pancreas was challenged by inducing severe necrotizing pancreatitis with retrograde infusion of taurocholate into the pancreatic duct. The course of necrohemorrhagic pancreatitis and survival of the rats to the challenge was monitored with time. Measurements and main results Forty-eight hours after the onset of edematous pancreatitis, the acute-phase response was strong, as judged by the overexpression of mRNA, which encoded the pancreatitis-associated protein I, and the resulting increase in concentrations of this protein in the pancreas. When necrotizing pancreatitis was induced, the survival rate was significantly higher than in the corresponding control group. In contrast, expression of the pancreatitis-associated protein I was not detectable after 2 hrs, indicating that the acute phase had not fully developed, nor after 168 hrs when the acute phase had ended. In both cases, challenge by necrotizing pancreatitis led to similar survival rates in cerulein-treated and control rats. Conclusions The acute-phase response of the pancreas seems to be a powerful emergency defense mechanism against further pancreatic aggression, as shown by the improved survival of the animals. The factors mediating this protection are unknown. Due to the strong overexpression of the pancreatitis-associated protein I during the climax of the acute phase, this protein might be involved in the defense mechanism.

The present study aimed to i) assess the prognostic value of monoethylglycinexylidide (MEGX) formation kinetics in predicting liver dysfunction in patients with severe sepsis, and ii) to compare it with other oxygen indices and with gastric mucosal pH (pHi). Twenty-seven patients meeting the criteria for severe sepsis were prospectively evaluated. Patients with haemodynamic instability, elevated liver enzymes (>2 × normal) and bilirubin levels (>3 mg/dl), coagulation disorders and gastro-intestinal bleeding were not included. A gastric tonometer (TRIP, Tonometrics, Worcester, MA, USA) was introduced in all patients. Gastric pHi was calculated using the Henderson-Hasselbalch equation. Oxygen delivery (DO2) was calculated by the simplified formula DO2 =CI×CaO2, where CI is cardiac index and CaO2 is arterial oxygen content. Oxygen consumption (VO2) was determined by indirect calculation of the product of CI and arteriovenous oxygen content difference. Plasma aspartate aminotransferase, alanine aminotra...

Background: Heart rate variability (HRV), a measure of cardiac autonomic balance seems to be linked to coronary artery disease (CAD). Impaired vagal input facilitates the generation of fatal arrhythmias and has a great impact on morbidity and mortality. The purpose of this study was to determine the relationship between perioperative HRV and the incidence of silent myocardial ischemia (SMI) and ventricular dysrhythmias in CAD–patients undergoing non–cardiac surgery. Methods: 31 patients were studied by continuous Holter electrocardiography preoperatively and again on the evening before surgery until postoperative day 3. Three frequency and one time domain measures of HRV (TP, 0.01–1.00 Hz: total power of the amplitude spectral plot; LF, 0.04–0.15 Hz: low–frequency power; HF, 0.15–0.40 Hz: high–frequency power; MeanRR: mean of all coupling RR–intervals between normal beats) as well as ischemic events and ventricular couplets and runs were computed. Results: Depending on the presence of ischemic episodes, each patient was assigned to either the no SMI–group (13 pts) or the SMI–group (18 pts). MeanRR, TP and LF significantly declined in both groups over time. The parasympathetically dominated index HF, however, only decreased in the SMI–group. Normalized HF power (HF/TP) even increased in the no SMI–group resulting in a postoperative decrease in LF/HF ratio. TP, LF, and HF inversely correlated with ischemia parameters whereas HF/ TP and HF/LF ratio correlated with the number of ventricular couplets. Incidence and severity of SMI significantly increased after surgery. Conclusion: Postoperatively, a prolonged vagal withdrawal occurred in CAD–patients exhibiting perioperative SMI. Whether the increased incidence of SMI after surgery in conjunction with the observed parasympathetic derangement contributes to adverse cardiac outcome still has to be determined.

Stroma-free hemoglobin solutions have been shown to maintain oxygen transport in the absence of red blood cells. This study was designed to investigate the impact of such solutions on hemodynamics and oxygen transport during progressive isovolemic hemodilution within and even beyond a clinically relevant range of hematocrit values.Prospective, randomized experimental study comparing a bovine hemoglobin-based oxygen carrier (bHBOC) with a conventional nonoxygen-carrying volume substitute (hydroxyethyl starch [HES]).Animal laboratory of a university cardiovascular research center.Splenectomized full-grown foxhounds, anesthetized with pentobarbital and piritramid.Twelve splenectomized foxhounds were anesthetized and mechanically ventilated. Catheters were placed for hemodilution, arterial and venous blood sampling, and hemodynamic measurements. The baseline hematocrit (Hct) value was adjusted to 0.35 by an initial isovolemic exchange of blood for identical volumes of HES (10% HES 200/0.5). Thereafter, the hematocrit was progressively reduced by isovolemic hemodilution using either HES (n = 6) or bHBOC (n = 6).Hemodynamic and laboratory parameters of oxygen transport were measured at Hct values of 0.30, 0.20, and 0.10. Oxygen content was directly estimated using an oxygen-specific fuel cell. Arterial oxygen content at an Hct value of 0.10 nearly doubled in bHBOC-treated dogs as compared with HES-diluted animals (p0.001). This gain in oxygen-carrying capacity was completely negated by a decrease in cardiac output (-32% Hct 0.35 v Hct 0.30; p0.001) immediately on the first infusion of bovine hemoglobin. Thus, oxygen delivery was significantly lower as compared with HES-treated dogs at Hct 0.30 and 0.20, but remained stable at a level of 60% of baseline until Hct was 0.10. Both the pulmonary and the systemic vascular resistances increased.Isovolemic hemodilution with bHBOC did not improve systemic oxygen delivery in comparison with a nonoxygen-carrying diluent (HES) in a range of Hct values down to 0.10. Unchanged mixed venous lactate levels and stable oxygen consumption indicate sufficiently maintained oxygen delivery. This might become advantageous in patients who are unable to adequately increase cardiac output during hemodilution.

To investigate whether modulation of the fatty acid profile can be achieved by the short-term infusion of a fish oil emulsion which may attenuate the pulmonary response to inflammatory stimulation. Changes of fatty acid pattern in-lung tissue and perfusate were analyzed and correlated with physiologic data after a 3-hr infusion of fish oil in comparison with a soybean oil preparation.Prospective, randomized, controlled trial.Experimental laboratory in a university teaching hospital.Forty standard breed rabbits of either gender.Isolated lungs from anesthetized rabbits were ventilated and recirculation-perfused (200 mL/min) with 200 mL of cell-free buffer solution to which either 2 mL of saline (control, n = 6), 2 mL of a 10% soybean oil preparation (n = 6), or 2 mL of a 10% fish oil emulsion (n = 6) were added. Samples of perfusate and lung tissue were collected for analysis of fatty acid composition. Tissue and perfusate fatty acid composition were analyzed by capillary gas chromatography. To study metabolic alterations in states of inflammatory stimulation, lungs of each group were stimulated with small doses of the calcium ionophore, A23187 (10(-8) M), during the 180-min lipid perfusion period and again after washing out the lipids by exchanging the perfusion fluid. Pulmonary arterial pressure and lung weight gain were monitored, and eicosanoids were analyzed in the perfusate.Free eicosapentaenoic acids increased several-fold in lung tissue and perfusate during a 3-hr infusion with fish oil. The intravenously administered n-3 fatty acids were rapidly hydrolyzed, as indicated by the appearance of substantial quantities of eicosapentaenoic acid in the perfusate free fatty acid fraction. This increase of perfusion levels of eicosapentaenoic acid was paralleled by an attenuated pressure increase and edema formation due to calcium ionophore challenge and an altered eicosanoid spectrum determined in the perfusate compared with soybean oil-treated lungs.Short-term n-3 lipid application (fish oil emulsion) exerts anti-inflammatory effects on lung vasculature, which may be due to the metabolism of eicosapentaenoic acid resulting in the generation of less potent inflammatory eicosanoids.

Of the animal models of human hemorrhagic shock, the volume-controlled hemorrhage model appears to come closer to the clinical situation than the commonly used pressure-controlled model, since the volumecontrolled model allows regulatory adjustment of blood pressure. The effects of volume-controlled hemorrhage on local cerebral blood flow (LCBF) of conscious animasl are not known. The present study investigates specific reaction patterns of LCBF in comparison to mean cerebral blood flow (CBF) during graded volume-controlled hemorrhagic shock in conscious rats. Conscious, spontaneously breathing, and minimally restrained rats were subjected to different degrees of volume-controlled hemorrhage (taking either 25, 30, 35, or 40 ml arterial blood/kg body weight (b.w.). Thirty minutes after the completion of blood taking, LCBF was determined during hemorrhagic hypovolemia using the autoradiographic iodo (14C) antipyrine method. A group of untreated rats (no hemorrhage) served as controls. LCBF was determined in 34 defined brain structures and mean CBF was calculated. During less severe hemorrhage (25 and 30 ml/kg b.w.) mean CBF was significantly higher than in the control group (+19% and +25%). During severe hemorrhage (35 and 40 ml/kg b.w.) mean CBF remained unchanged compared to the control values, although significant increases in LCBF could be detected in many of the brain structures analyzed (maximum +44%). The mean coefficient of variation of CBF was increased, indicating a larger heterogeneity of LCBF values at shed blood volumes of 35 and 40 ml/kg b.w. A comprehensive and novel description of the local distribution of CBF during graded volume-controlled hemorrhage in conscious rats shows unexpected increases in LCBF and mean CBF. This “hypovolemic cerebral hyperemia” might be caused by endogenous hemodilution, thus maintaining the blood supply to the brain during hypovolemic shock.

The aim of this study was to investigate whether the oxygen radical scavenger N-acetylcysteine (N-AC) impairs bacterial clearance, thus predisposing the host to increased risk of disease. Blood clearance of Escherichia coli and organ colonization were investigated in anaesthetized rabbits after pretreatment with N-AC (250 mg kg-1 body weight, n= 16) and in sham-operated animals (n= 12). To enable quantification of the clearance process, defined numbers of exogenous E. coli [1.3 times 108 colony-forming units (CFUs)] were injected intravenously. Parameters monitored were kinetics of bacterial elimination from the blood, and polymorphonuclear leucocyte (PMN) oxidative burst activity. Samples of liver, kidney, spleen and lung were collected for bacterial counts. Compared with controls, pretreatment with N-AC resulted in delayed bacterial elimination from blood and higher organ colonization with increased numbers of E. coli in liver, lung and kidney (P < 0.05). N-AC treatment was associated with a suppressed PMN oxidative burst activity. Impaired bacterial clearance and enhanced organ colonization in N-AC-treated animals correlated with reduced oxidative burst activity, suggesting impaired granulocyte-dependent bacterial killing due to N-AC application.

Experimental studies have shown that in traffic accidents with frontal impact the new airbag system can significantly reduce the incidence of severe injuries and fatal outcome. The question of whether the airbag itself induces specific patterns of injury needs further investigation. Two cases of traffic accidents with airbag protection are presented here. The first case report clearly shows the life-saving and injury-reducing effect of the airbag system in a traffic accident with frontal impact at 100 km/h. In the second case only minor injuries of the face were diagnosed initially. Hemodynamic instability occurred after 3 h of hospitalization due to rupture of the azygos vein. Analysis of the presented cases shows that, besides the well-known benefits, there are certain injury patterns that seem to be related to the use of airbags. These have not been described before. It is concluded that patients who were involved in traffic accidents with airbag deployment have to be hospitalized and followed up carefully over time, even though they are initially stable, as potentially fatal sequelae of deceleration trauma can occur later. In our opinion it is not possible to estimate the severity of airbag-associated injuries with conventional methods.

(1995). Alterations of pulmonary capillary filtration and leukotriene synthesis due to infusion of a lipid emulsion enriched with Omega-3-fatty acids. Clinical Intensive Care: Vol. 6, No. 3, pp. 112-120.

The effects of resuscitation fluids on the brain have been investigated in previous studies by global measurements of cerebral blood flow and metabolism. In this study we have examined the effects of a novel haemoglobin-based oxygen carrier on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) after resuscitation from a volume-controlled haemorrhage of 30 min (3.0 ml/100 g body weight) with ultrapurified, polymerized, bovine haemoglobin (UPBHB). LCBF and LCGU were measured in 34 brain structures of conscious rats 2 h after resuscitation using quantitative iodo(14C)antipyrine and 2-(14C)-deoxy-D-glucose methods. The data were compared with a control group without haemorrhage and fluid resuscitation. In the haemorrhage group, LCBF increased after resuscitation by 12-56% in the different brain structures (mean 36%). LCGU changed less (0 to +18%, mean +9%). In the control group there was a close relationship between LCGU and LCBF (r = 0.95). After fluid resuscitation the relationship was preserved (r = 0.95), although it was reset at a higher ratio of LCBF to LCGU (P0.05). We conclude that fluid resuscitation of a 30 min volume-controlled haemorrhage using the haemoglobin-based oxygen carrier, UPBHB, induced a moderate degree of heterogeneity in the resulting changes of LCGU and LCBF. Local disturbances of cerebral blood flow or metabolism were not observed.

Whether the increase in cerebral blood flow measured after hemodilution is mediated by a decrease in blood viscosity or in oxygen delivery to the brain is debated. In the present study, blood was replaced by an oxygen-carrying blood substitute, ultrapurified, polymerized, bovine hemoglobin (UPBHB). In contrast to normal blood, UPBHB yields a constant and defined viscosity in the brain circulation, since its viscosity is not dependent on the shear rate. CBF was determined after blood exchange with UPBHB in one group of conscious rats (UPBHB group) and in another group of blood-exchanged conscious rats in which viscosity was increased fourfold by the addition of 2% polyvinylpyrrolidone (PVP), mw 750,000 (UPBHB-PVP group). Local CBF (LCBF) was measured in 34 brain structures by means of the quantitative iodo(14C)antipyrine method. After blood replacement, systemic parameters such as cardiac index, arterial blood pressure, blood gases, and acid-base status were not different between the UPBHB and the UPBHB-PVP groups. In particular, arterial oxygen content was similar in both groups. Compared with a control group without blood exchange, LCBF was increased after blood exchange in the different brain structures by 60–102% (UPBHB group) and by 33–101% (UPBHB-PVP group). Mean CBF was increased by 77% in the UPBHB group and by 69% in the UPBHB-PVP group. No significant differences were observed in the values of LCBF or mean CBF between the UPBHB group and the UPBHB-PVP group. The results show that a fourfold variation in the viscosity of a Newtonian blood substitute does not result in differences in CBF values. It is concluded that blood viscosity is less important to CBF than hitherto postulated.

The purpose of the study was to investigate the potential influence of endotoxin and tumor necrosis factor (TNF) on immune function in terms of systemic 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 (1.3 x 10(8) CFU) were injected intravenously 60 min after bolus application of TNF (4 x 10(5) U, n = 6), after infusion of endotoxin (40 micrograms/kg of body weight) for 1 h (n = 6) or 4 h (n = 6), or after saline infusion (controls, n = 6). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. Endotoxin infusion produced a significant delay in blood clearance compared with saline and TNF pretreatment. The diminished systemic bacterial elimination was associated with significantly higher numbers of E. coli in the organs, thus reflecting reticuloendothelial system dysfunction. TNF had no major influence on the elimination kinetics of bacteria but affected the tissue distribution pattern with increased accumulation of E. coli in the lung (up to 100-fold of control values; P < 0.001).

Different pathomechanisms in the development of pulmonary edema are being discussed. We investigated the effect of pathogenetically varying forms of edema on lung vascular barrier function in isolated cell-free perfused rabbit lungs. As an index of permeability, capillary filtration coefficients (Kfc) were determined from the slope of lung weight change over periods of stepwise venous pressure elevation (5, 7.5, and 10 mmHg) before (controls) and 60 min after edema induction. Edema was induced by venous congestion (n = 6), by application of arachidonic acid in the presence of diclofenac sodium (n = 6), and by elastase application (n = 6). Control values ranged from 0.28 to 0.51 ml.min-1 x mmHg-1 x 100 g-1. Kfc was significantly enhanced after edema induction up to 243% of control value in the hydrostatic edema, 357% in the arachidonic acid edema, and 594% in the elastase edema. When the alterations in capillary filtration due to the different types of edema were compared, Kfc was significantly higher in the proteinase edema, indicating an irreversibly damaged barrier function. These data exemplify different pathophysiological characteristics due to the pathogenesis of interstitial edema formation.

Humidification of inspiratory gases under anaesthetic conditions still is a matter of controversial discussion. Physiological humidification and heating of breathing air are preconditions for mucociliary clearance, pulmonary cleaning and defence mechanisms. These functions of the upper respiratory tract are eliminated by application of artificial airways. In general the humidification of inspiratory gases should not remain under 70% of relative air humidity at 37 degrees C. Under clinical conditions it is problematic to ensure sufficiently rapid and reproducible measurements of humidity during breathing cycles. We developed a measuring method that enables to make these measurements without big mechanical device. Aim of this investigation was to measure air humidity in typical semiclosed systems during anaesthesia and semiopen CPAP-respiration. The necessity and efficiency of a heat and moisture exchanger (HME) was to be investigated as well. After approximately 5 minutes there was an inspiratory relative air humidity not below 70% at 28 degrees C (19 mg H2O/l humid air) within the breathing circuit with CO2 double-absorber. By using an HME it is possible to increase relative air humidity within this system to 86% at 29.5 degrees C (25 mg/l). After one hour's respiration with this system without HME a relative humidity of 87% at 30 degrees C (26 mg/l) is reached after replaced HME. Initial relative humidity in a semiopen CPAP-system is about 12% at 28 degrees C (3 mg/l). This is increased to 85% at 29.5 degrees C (25 mg/l) after 15 minutes respiration with HME.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary Organ dysfunction is a major clinical problem after lung transplantation. Prolonged cold ischaemia and reperfusion injury are believed to play a central role in this complication. The influence of cold preservation on subsequent warm reperfusion was studied in an isolated, ventilated and perfused rat lung. Rat lungs were flushed with cold Perfadex-solution and stored at 4°C for different time periods. Thereafter lungs were perfused and ventilated for up to 3 h. Physiological parameters, production of inflammatory mediators and leucocyte infiltration were measured before and after perfusion. Lungs subjected to a cold ischaemia time of up to 6 h showed stable physiological conditions when perfused for 3 h. However, cold-ischaemia time beyond 6 h resulted in profound tissue oedema, thereby impairing ventilation and perfusion. Warm reperfusion and ventilation per se induced a strong inflammatory response, as demonstrated by a significant up-regulation of chemokines and adhesion molecules (cytokine-induced chemoattractant-1, intracellular adhesion molecule and endothelial leucocyte adhesion molecule), accompanied by enhanced leucocyte infiltration. Although the up-regulation of inflammatory mediators was blunted in lungs that were subjected to cold ischaemia, this did not influence leucocyte infiltration. In fact, cold ischaemia time correlated with leucocyte sequestration. Although cold preservation inhibits the expression of inflammatory mediators it does not affect leucocyte sequestration during warm reperfusion. Cold preservation might cause impairment of the endothelial barrier function, as evidenced by tissue oedema and profound leucocyte infiltration.

Objective: To evaluate the efficacy and safety of the natural platelet-activating factor receptor antagonist, BN 52021 (ginkgolide B) in the treatment of patients with severe sepsis related to Gram-negative and mixed bacterial infection. Design and setting: Prospective, randomised, double-blind, placebo-controlled, multicentre study carried out in 13 academic medical intensive care centres in Germany with up to 14 patients per centre. Patients: 88 patients with severe sepsis under standard medical and surgical care: nine patients with pure Gram-positive infection, 79 patients with Gram-negative or mixed bacterial infections (subgroup for which efficacy was to be established). Interventions: Patients were randomised to receive either placebo or BN 52021 1.25 mg/kg body weight intravenously every 12h over a 4-day period in addition to their standard medical and surgical care. Main outcome measures and results: The primary efficacy variable was the 28-day all-cause mortality rate. The treatment groups were similar with respect to demographic data and prognostic factors influencing the outcome except for bodyweight and adequacy of antibiotic therapy. Analysis of patients with Gram-negative or mixed bacterial infection, for which efficacy was to be established, resulted in a 28-day all-cause mortality of 42.5% in the placebo group (n = 40; 17 deaths) versus 38.5% in the BN 52021 group (n = 39; 15 deaths). Among all randomised patients, the 28-day all-cause mortality rate was 40.9% in the placebo group (n = 44; 18 deaths) and 38.6% in the BN 52021 group (n = 44; 17 deaths). There were no differences in frequency and severity of adverse events between the two treatment groups. Conclusions: Four-day administration of BN 52021 failed to demonstrate a statistically significant reduction in mortality in patients with severe sepsis suspected or confirmed to be related to infections other than Gram-positive bacterial infection.

The aim of the present study was to show the influence of cerebral oxygenation (regional cerebral oxygen saturation rSO(2) by near infrared spectroscopy) and of the nocturnal arterial oxygen saturation (SatO(2) by pulse oximetry) on the restitution of cognitive functions in patients aged between 40 and 85 years scheduled for elective hip arthroplasty.A total of 40 patients (ASA II) were randomized to be operated either in general anaesthesia or regional anaesthesia. The patients were additionally classified by age (40-64 years and 65-85 years). Cognitive functions were tested 14-16 h pre-operatively (t0), 1.5 h post-operatively (t1) and at the first and third postoperative days (t2 and t3). During testing, as well as during surgery and postoperatively until t1, rSO(2) was continuously measured. SatO(2) was measured in the night before surgery (N0) and for 3 nights after surgery (N1, N2, N3) between 22.00 p.m. and 5.00 a.m. These measurements were divided into interval groups (80-83%, 84-87%, 88-91%, 92-95%, 96-100%).Almost all cognitive functions were significantly reduced at t1 in all groups compared to t0, but recovered up to the third postoperative day (t3). RSO(2) in contrast was significantly reduced in all groups compared to t0 at the third postoperative day (t3). The relative proportion of the intervals compared to the total measurement time for SatO(2) shifted in both anaesthesia procedures: before surgery (N0) the most frequented interval was 96-100%, after surgery (N1, N2) it was 88-91%. There was no correlation between rSO(2), the restitution of the tested cognitive functions and SatO(2).Cognitive functions recovered completely during the first 3 postoperative days in patients scheduled for elective hip surgery under general or regional anaesthesia regardless of age and type of anaesthesia. This restitution of cognition occurred despite a significant decrease of cerebral oxygenation (rSO(2)) and despite an increase of nocturnal hypoxaemic intervals. Changes of the rsO(2) up to 3% below the baseline values (measured by NIRS) do not predict cognitive restitution. A minimal limiting value of the rSO(2) could not be defined.

Inflammatory responses during sepsis are determined by leucocyte recruitment into inflamed tissues. Both chemokines and adhesion molecules are believed to be involved in this process. As fractalkine exists as transmembrane protein with cell adhesion properties and as soluble chemotactic factor, the present study was conducted to study the role of fractalkine, produced by microvascular and macrovascular endothelial cells, in neutrophil recruitment. Lung microvascular endothelial cells (LMVECs) stimulated with lipopolysaccharide, tumour necrosis factor-alpha or interleukin-1 (IL-1) produced much more fractalkine compared with the macrovascular human umbilical vein endothelial cells (HUVECs). No differences were found between microvascular endothelial cells of different organs. Chemotactic activity in supernatants was significantly stronger in stimulated LMVEC when compared with HUVEC. Although recombinant fractalkine induced migration of neutrophils, IL-8 and monocyte chemoattractant protein-1 were found to be more strictly required. In vivo fractalkine was strongly upregulated in septic lung and kidney. Our data suggest that fractalkine production per se does not explain the preference for inflammation in the lung of septic patients.

„Auch in Deutschland trifft man hie und da eine gewisse Sehnsucht nach solchen Narkosespezialisten, ohne dass es indessen gelungen ware, diese Species irgendwo tatsachlich lebendig zu erhalten“.(Max v. Brunn, 1875–1924; [74])

Quality of care and costs are getting closer together. Whereas costs and quality management did not play a substantial role 30 years ago, the consumption of resources nowadays is part of the outcome of quality of care. The definition of quality must be seen in the dimensions of structure, process and result. Resulting from newly developed clinical practice, guidelines are planned as instruments for cost containment in near future. Those guidelines may end up in a quality management system. The most wellknown european basic of such a quality management system are the DIN EN ISO 9000 f and the EFQM. The ISO 9001 and the European Quality Award became the most common base of evaluation for certification of quality management systems in Organisations European wide. Whereas the ISO 9001 does not give any information about the real achieved quality, the European Quality Award reflects the process. Guidelines are necessary to prove the cost effectiveness of measures of quality control and quality assurance since too much quality control and assurance may result in increased overall consumption of resources, leading to a reduction in the quality of care when ensuring that the overall budget is covered.

It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics.Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls.During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68.Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.

The aim of the present study was to show the influence of the parameters of gas exchange (arterial oxygen pressure paO2, arterial oxygen saturation SatO2) and haemodynamics (arterial systolic and mean blood pressure RRs and MAP) on the restitution of cognitive functions in geriatric patients scheduled for elective hip arthroplasty.A total of 30 patients (70 years, ASA II) were randomized to be operated either in regional anaesthesia (n = 15) or general anaesthesia (n = 15). PaO2 (by capillary blood gas analysis), RRs and MAP (by oscillometry) were measured 15 and 90 minutes after arrival in the recovery unit (t1 and t2), 24 and 72 hours postoperatively (t3 and t4), and cognitive functions were tested. Intraoperatively, throughout the day and the first night after surgery we measured satO2 by continuous pulse oximetry. We recorded MAP and RRs by oscillometry every 3 minutes during the operation and every 15 minutes for the rest of that day and night.The parameters of gas exchange and haemodynamics did not differ among the groups. PaO2 was significantly reduced in both groups compared to baseline 24 hours postoperatively (t3) and remained low until 72 hours postoperatively (t4). Nearly all cognitive functions were significantly reduced in both groups compared to baseline 15 and 90 minutes after arrival in the recovery unit (t1 and t2), but recovered on the first postoperative day (t3). Both groups kept deficits in verbal memory and reading capacity up to the third postoperative day (t4). There was no correlation between the physiological parameters and the restitution of the tested cognitive functions.The restitution of cognitive functions during the first three postoperative days in geriatric patients scheduled for elective hip surgery does not depend on the anaesthetic technique. According to our results regional anaesthesia does not show any advantage for geriatric patients undergoing elective hip arthroplasty.

The purpose of the study was to investigate the potential influence of the anaesthetic agent propofol on immune function in terms of systemic clearance and organ distribution of injected Escherichia coli in a rabbit model.Defined numbers of E. coli (1.3 x 10(8) colony-forming units, CFU) were injected intravenously 1 h after starting a 4-h infusion of the anaesthetic propofol (2 ml.kg-1.h-1, Disoprivan 1%; n = 6)) or after saline application (n = 6). As propofol is formulated in a 10% lipid emulsion, the lipid vehicle Intralipid (2 ml.kg-1.h-1; n = 6) alone was investigated in a separate group. Parameters monitored were arterial pressure and rates of bacterial elimination from the blood. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, spleen, lung, and kidney were collected for microbiological examinations.Compared to saline-treated animals, infusion of propofol induced increased accumulation of E. coli in lung and spleen, thus reflecting reticuloendothelial system dysfunction.As the lipid emulsion by itself induced the same effects, the impaired immune function due to propofol is thought to be attributed to its solvent Intralipid.

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 cy-clooxygenase 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 LU135 252 significantly reduced the pressure reaction after air embolism (p

The effects of bradykinin, histamine and serotonin on vascular resistance and microvascular permeability were investigated in isolated cell-free perfused rabbit lungs. The capillary filtration coefficient was determined from the slope of lung weight changes over periods of venous pressure elevation before application of bradykinin (n = 6), histamine (n = 6) and serotonin (n = 6), and 5, 20 and 50 min afterwards. To prevent rapid inactivation of bradykinin by the angiotensin-converting enzyme in the pulmonary circulation, the bradykinin effects were additionally studied in the presence of the angiotensin-converting enzyme inhibitor captopril (n = 6). Bolus application of each substance resulted in a short-lasting increase in the pulmonary vascular resistance (3.7-9.1 mmHg). Which was most pronounced in the bradykinin+captopril group. The capillary filtration coefficient was significantly increased after histamine application, and to an even greater extent after serotonin application, whereas bradykinin on its own, as well as bradykinin given in the presence of captopril, had no measurable influence on capillary filtration in the lung. As a result of the bradykinin challenge, there was an immediate massive generation of prostacyclin, which could not be further augmented by a application. Histamine injection entailed a delayed onset of prostacyclin generation after the second stimulation, whereas no prostacyclin increase was measured in the serotonin-treated lungs. Thromboxane A2 generation was exclusively observed after the first serotonin application. The data exemplify different pathophysiological characteristics of bradykinin, histamine and serotonin on lung barrier function. Histamine and serotonin induce oedema formation by enhancing microvascular permeability, whereas bradykinin does not.

Vaskulare Endothelzellen kleiden in einer dunnen einlagigen Schicht das gesamte Blutgefassystem vom Herzen bis zu den kleinsten Kapillaren aus. Die Zellschicht eines 70 kg Erwachsenen bedeckt ca. 1000m2 und wiegt ca. 1kg.

Purpose of the study was to investigate the potential influence of norepinephrine (NE) on immune functions in terms of systemic and organ-specific bacterial clearance in rabbits.To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) CFU) were injected intravenously 60 min after starting the NE infusion at a low dose (1 microgram/kg per min, n = 6), causing an increase (30 mmHg) in mean arterial pressure without affecting the oxygen uptake, and at a higher dose (7.5 micrograms/kg per min, n = 6), resulting in a marked decrease (20%) in oxygen uptake, after infusion of NaCl solution (control, n = 6). In additional experiments (n = 6) NE (1 microgram/kg per min) was tested in endotoxemia induced by simultaneous infusion of endotoxin (40 micrograms/kg per h). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts.NE infusion resulted in a dose-dependent prolonged elimination of the injected E. coli from the blood and in significantly higher (p0.05) numbers of CFU in liver and lung compared to the controls. Significant impairment of bacterial clearance was found after shock-producing endotoxemia, whereas simultaneous infusion of NE and endotoxin caused only a slightly delayed blood clearance of the injected bacteria.NE dose dependently affected bacterial clearance, which might be due to ischemia-derived hypoxic impairment of the phagocytosis and lysis function of the reticuloendothelial system, whereas NE improved elimination of bacteria in a state of endotoxic shock.

Experimental studies have shown that in traffic accidents with frontal impact the new airbag system can significantly reduce the incidence of severe injuries and fatal outcome. The question of whether the airbag itself induces specific patterns of injury needs further investigation. Two cases of traffic accidents with airbag protection are presented here. The first case report clearly shows the life-saving and injury-reducing effect of the airbag system in a traffic accident with frontal impact at 100 km/h. In the second case only minor injuries of the face were diagnosed initially. Hemodynamic instability occurred after 3 h of hospitalization due to rupture of the azygos vein. Analysis of the presented cases shows that, besides the well-known benefits, there are certain injury patterns that seem to be related to the use of airbags. These have not been described before. It is concluded that patients who were involved in traffic accidents with airbag deployment have to be hospitalized and followed up carefully over time, even though they are initially stable, as potentially fatal sequelae of deceleration trauma can occur later. In our opinion it is not possible to estimate the severity of airbag-associated injuries with conventional methods.

To assess the effects of the cyclooxygenase inhibitor diclofenac in a canine model of pulmonary occlusion and reperfusion of the left lower lobe (LLL).Twelve adult beagle dogs (13-17 kg) were randomly assigned to a control group (n = 6) and a diclofenac-treated group (n = 6). Animals in the treatment group received 20 mg diclofenac sodium/kg as a single dose both before the experiment and at the end of surgical preparation; six animals served as controls.In the anesthetized animals, the left upper and middle lobes were resected. Circulation and ventilation of the LLL were selectively blocked by clamping. Complete occlusion of the LLL (30 min) was followed by periods of selective reperfusion (10 min, RP) and combined reperfusion and reventilation (120 min, RP/RV).Reperfusion of the LLL resulted in a significant increase in pulmonary arterial pressure (Ppa) in the early RP/RV period as compared to baseline values (25.3 +/- 4.7 vs 15.8 +/- 1.9 mmHg, p0.05, paired t-test). This increase was significantly inhibited in the diclofenac-treated animals (17.0 +/- 2.0 mmHg, p0.01 vs controls, ANOVA). Gravimetrically determined extravascular lung water (EVLW) showed no significant difference in the continuously ventilated lobes of the right lung between diclofenac-treated animals (3.8 ml/g dry weight) and controls (3.9 +/- 0.9 ml/g dry weight) at the end of the experiment. EVLW, however, increased significantly in the LLL of control animals after 2 h of combined reperfusion and reventilation, whereas this increase was significantly inhibited in the diclofenac-treated animals (4.5 +/- 0.7 ml/g dry weight in the diclofenac group vs 6.5 +/- 1.3 ml/g dry weight in the control group, p0.05).Diclofenac inhibits the increase in both pulmonary arterial pressure and EVLW during reperfusion and reventilation of LLL. Thus, these changes appear to be mediated by cyclooxygenase metabolites.

In search of new possibilities to prevent acute inflammatory vascular reaction, we examined the effect of two selective B2 receptor antagonists, CP 0127 ([Bissuccimidohexane (L-Cys6)-1] and HOE 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]BK), on changes in perfusion pressure and on edema formation caused by bradykinin (BK) in the isolated perfused rabbit hindlimbs. CP 0127 and HOE 140 were added to the perfusion fluid 2 min prior to the first BK-administration (5 x 10(-9) mol/l). A second BK-stimulation was performed after 30 minutes. The antagonists were tested in groups of 6 experiments each at concentrations of 10(-6) mol/l, 5 x 10(-9) mol/l and 10(-10) mol/l. CP 0127 was also tested in a concentration of 10(-8) mol/l. The application of BK resulted in an acute decrease of the mean arterial pressure and in a continual edema formation, reflected by an increase of organ weight (controls, n = 6). Pretreatment with CP 0127 as well as with HOE 140 attenuated dose-dependently the BK-induced vasodilation (p0.005) and edema formation. The current results indicate that CP 0127 and HOE 140 are able to reduce BK-induced effects on vascular tone and edema formation.

Despite its worldwide propagation, external chest compression is of limited efficacy. Recently a new method of cardiac resuscitation, active compression-decompression (ACD), was presented. In animals and a small series of patients resuscitated within the hospital ACD proved to augment blood flow during cardiac resuscitation as a result of greater intrathoracic pressure gradients.We investigated whether ACD does provide superior survival in patients suffering from out-of-hospital cardiac arrest.Doctors and paramedics of the mobile intensive care unit at Mannheim University Hospital were trained in the new method. 56 patients were randomly assigned to either standard chest compression according to recommendations of the American Heart Association, AHA (Group I, 30 patients) or to ACD (Group II, 26 patients). ACD was performed by use of a hand-held suction device (CardioPump, Ambu Int.). Compression (30-50 kp) and decompression (10-15 kp) were alternately applied to the patients' chest with a frequency of 80/min. Duration of compression was 50% of the cycle. In both groups advanced life support was performed according to AHA standards.In Group I, 40% of the patients could be resuscitated; and 13.3% were discharged from hospital. In Group II, 38.5% of the patients regained spontaneous circulation, and 11.5% of the patients were discharged. (Group I vs. Group II: n.s.). One patient in each group survived with a severe neurological deficit. ACD caused greater physical efforts than standard chest compression. Furthermore ACD was difficult to perform in patients with ventricular fibrillation once electrode gel had been used. ACD was not feasible in five patients because of large breast (four women) and kyphoscoliosis (one patient). The rate of serious complications was lower in Group II.Methods to verify the efficacy of ACD in dummy training should be developed. Paramedics performing ACD should relieve each other every 5 minutes. In patients resuscitated by ACD self-adhesive defibrillation paddles instead of electrode gel should be used. Modifications in the design of the CardioPump are desirable to enhance the efficacy of ACD. With regard to future multicentre trials all paramedics should be skilled in the new technique to reach more patients in a shorter period of time.

Oxidized glutathione (GSSG) but not its reduced form (GSH) is taken up by intact myocardial cells, and is rapidly converted into GSH. Reduced glutathione is an important intracellular defense against oxygen-derived free radicals and has been found to enhance calcium sensitivity in skinned cardiac fibers. We have investigated the effects of intravenous GSSG on left ventricular systolic pressure, maximal rate of rise of pressure and regional segment-shortening in dogs subjected to occlusion of the left anterior descending artery for 30 minutes, followed by 45 minutes reperfusion. Starting 10 minutes before reperfusion, the dogs were randomly treated with either GSSG (100 mM, 5 ml/min, n = 5) or Ringer's solution (5 ml/min, n = 5) until 30 minutes of reperfusion. Myocardial blood flow was measured by radioactive microspheres. Infusion of GSSG increased total glutathione content in both ischemic (47 +/- 16 mumol/g protein) and nonischemic myocardium (71 +/- 17 mumol/g protein) as compared to controls (23 +/- 2 mumol/g protein, p0.05). In both groups paradoxical wall motion occurred in the ischemic region during occlusion. On reperfusion, regional dyskinesia persisted in controls; while, in glutathione-treated dogs, systolic segment-shortening reached half the baseline values (p0.05, treated vs controls, at 15, 30, 45 minutes reperfusion). During ischemia the area of pressure-length loops, obtained from simultaneous recordings of left ventricular pressure and regional segment length, decreased to 30 +/- 7% of baseline in controls and to 40 +/- 18% of baseline in GSSG-treated animals. After 45 minutes reperfusion it was restored to 78 +/- 22% baseline in treated hearts but was still 36 +/- 16 of baseline in controls (p0.05). We conclude that infusion of GSSG increases the intracellular stores of glutathione and improves the contractile state of postischemic myocardium.

Small volumes of hypertonic NaCl-solutions have been proven to restore haemodynamics in hypovolemic shock patients. Topic of this study was to investigate whether bolus application of 7.5% NaCl-6.5% starch-solution (HSS) apart from its relevance in shock might be an effective therapy in oedema. Considering differential therapeutic aspects, the volume effects of 7.2 ml HSS were tested in three types of oedema: hydrostatic oedema induced by venous congestion (n = 6), oedema caused by bradykinin injection (n = 6), and proteinase-induced oedema (n = 6). The arterial, venous pressure and weight changes indicating volume shifts between intra- and extravascular space were continuously monitored in 36 isolated perfused rabbit hindlimbs. Oedema formation was induced corresponding to a weight gain of 18-20 g. Subsequently 7.2 ml HSS were injected into the extracorporeal circulation system containing 200 ml cell free, isoosmotic perfusate. Six experiments of each oedema group without HSS-application served as controls. 75-100% of oedema formation could be remobilised via bolus application of HSS within 5 min in all types of oedema. A persisting weight reduction was detectable in the hydrostatic and bradykinin oedema, whereas in the elastase oedema the initial weight loss was followed by a regain of weight up to 180% of initial oedema formation at 120 min after HSS-application. The results show that, due to the osmotic gradient induced by bolus application of HSS, the hydrostatic and bradykinin oedema can be permanently remobilised, whereas the therapeutic effect during proteinase oedema is only short-lasting due to an irreversible damage of barrier function.

Background: The aim of this study was to investigate whether the pulmonary response to inflammatory stimulation, resulting in increased vascular resistance and permeability, could be attenuated by short-term infusion of triglycerides containing ω-3 fatty acids. With the concept of altering the composition of membrane phospholipids in such a manner that stimulation resulted in the release of less vasoconstrictive and permeability-enhancing metabolites of eicosapentaenoic acid instead of those of arachidonic acid (AA), the parenteral application of a lipid emulsion prepared from fish oil (Omegavenös®) was tested in comparison with a soy oil preparation (Lipovenös®). Methods: Isolated lungs from anesthetized rabbits were ventilated and recircuatingly perfused (200 ml/min) with 200 ml cell-free buffer solution to which either 2 ml saline (controls, n = 6), 2 ml Lipovenös 10% (n = 6) or 2 ml Omegavenös 10% (n = 6) were added. To study the possible metabolic alterations in states of an enhanced AA turnover, lungs of each group were stimulated with smaller doses of A23187 (10–8M) during the 180 -min lipid perfusion period, followed by a 10 times higher calcium ionophore A 23187 (10–7M) challenge after washing out the lipids by exchange of perfusion fluid. Pulmonary artery pressure (PAP) and the lung weight gain indicating edema formation were monitored, and eicosanoids were analyzed in samples of the perfusate. Results: Upon A23187 injection lung weight gain and PAP increase were significantly reduced (50%) in Omegavenös-perfused lungs in comparison with controls and Lipovenös treatment. The vascular reactions were accompanied by a shifting from LTC4 to LTC5 during and after Omegavenös perfusion. Conclusion: The data demonstrate that ω-3 fatty acids seem to be incorporated into the phospholipid pool of the pulmonary tissue, even after short-term infusion (3 h) resulting in an attenuated pressure reaction and edema formation due to an altered spectrum of metabolites in the case of inflammatory stimulation.