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Terroranschlage mit Massenanfall von Verletzten (TMANV) haben ein besonderes Anforderungsprofil. Krankenhauser werden bei Terrorlage anders als beim klassischen Massenanfall unangekundigt von hohen Verletztenanzahlen uberlaufen. Besonders kleinere Kliniken stellt dies vor Probleme. Ziel unserer Arbeit war, in einer kommunalen Klinik in kurzer Zeit einen Behandlungsplatz verlasslich einzurichten. Unter Bezugnahme auf Expertenkonsens, publizierte Versorgungsstrategien und Fallberichte stellen wir ein Konzept zur klinischen Erstversorgung von 8 Schwerverletzten vor. Der operative Betrieb im Alltagsgeschaft lastet kleinere kommunale Kliniken nahezu vollstandig aus. Wirksame und umsetzbare Vorhaltungen fur TMANV-Szenarien sind schwer realisierbar. Kurze Wege und die Verfugbarkeit im Notfall machen den „Behandlungsplatz im Aufwachraum“ zum attraktiven Losungsansatz. Der Aufwachraum einer Klinik bietet den Platz sowie die notwendige Logistik und ist praktisch 24 h schnell verfugbar. Gasversorgung, Monitoranlage, sach- und ortskundiges Personal sind vor Ort. Acht dezentral auf den peripheren Stationen der Klinik gelagerte Notfallrucksacke werden beim TMANV im Austausch gegen die postoperativ uberwachten Patienten in den Aufwachraum verbracht. Die dort abgeholten Patienten sind damit dezentralisiert auf den Normalstationen adaquat weiterversorgt. Im Gegenzug ist der Aufwachraum freigeraumt. Das dortige Personal ist verfugbar und das Material vor Ort. Die mobile, traumaspezifische Rucksackausstattung ermoglicht in Kombination mit dem Aufwachraummonitoring, schnell, flexibel und wirksam auf mehrere Schwerstverletzte vorbereitet zu sein. Die Ortswahl Aufwachraum und die Nutzung des Materials im Routinenotfallbetrieb bedingen zweierlei: Die Akteure sind mit Material und Raumlichkeiten vertraut und man ist im Ernstfall in der Tat handlungsfahig. Das Konzept ist soweit moglich wirtschaftlich. Ein neues „Gunzburger Modell“ bei Vorliegen eines TMANV in der Klinik der Regelversorgung konnte lauten: Behandlung mit Rucksack im Aufwachraum.

ZusammenfassungDer Notarzt muss für eine effektive und erfolgreiche Einsatzabwicklung die lokalen Gegebenheiten, die Fähigkeiten der Feuerwehren und die Standardrettungstechniken kennen. Der vorliegende Artikel geht auf die Rettung mit Hubrettungsmitteln und einfaches Retten aus Höhen und Tiefen mit der Schleifkorbtrage ein.

Background Increased vascular permeability is a characteristic feature of sepsis which, in the past, has been ascribed exclusively to a malfunction of endothelial cells. However, recently it has become evident that the endothelial glycocalyx is of considerable importance concerning various aspects of vascular physiology, e.g. the vascular barrier and inflammation. Heparan sulfate, one of its essential components is characteristically traceable in blood, in case the endothelial glycocalyx is damaged or destroyed. Methods In 15 pigs we investigated whether the administration of endotoxin from gram-negative bacteria (Escherichia coli) results in increased serum levels of heparan sulfate, signalizing a shedding of the glycocalyx. In addition, markers of inflammation (white blood cell count, platelet count, tumour necrosis factor-α and interleukin-6) were evaluated over an observation period of 6 hours. Results Serum heparan sulfate concentrations significantly increased over time in the endotoxin group and were significantly elevated in comparison to the control group 6 hours after administration of endotoxin (p < 0.001). In the endotoxin group all markers of inflammation significantly changed during the time course. Conclusions The administration of bacterial endotoxin induced a significant rise in degradation products of the endothelial glycocalyx.

The aim was, to identify an estimate of left ventricular contractility derived from the aortic pressure wave without load changing manoeuvres. For this purpose, left ventricular contractility was assessed with several aortic pressure wave form derived parameters and was compared to standard parameters of left ventricular contractility (conductance technique) in an experimental study. Measurements were taken during baseline, after beta-stimulation and after injection of a beta-antagonist. The initial and the secondary tangent, the area under the aortic pressure, and the stroke volume were correlated with the endsystolic elastance, a mainly load independent measure of left ventricular contractility: The initial tangent of the aortic pressure increase correlated significantly with the endsystolic elastance (r = 0.54, P0.05). The initial tangent of the aortic pressure increase was significantly increased from baseline at beta-stimulation (from 20.2 +/- 4.7 to 36.4 +/- 6.8 mmHg s(-1), P0.05) and decreased after injection of a beta-antagonist (from 20.2 +/- 4.7 to 12.3 +/- 2.0, P0.05). Thus, we conclude that the initial tangent of the aortic pressure increase is a valid estimate of left ventricular contractility in piglets.

Background: Halogenated anaesthetics have been shown to reduce ischaemia–reperfusion injuries in various organs due to pre- and post-conditioning mechanisms. We compared volatile and total intravenous anaesthesia with regard to their effect on remote pulmonary injury after thoracic aortic occlusion and reperfusion. Methods: Eighteen pigs were randomized after sternotomy and laparotomy (fentanyl–midazolam anaesthesia) to receive either sevoflurane or propofol in an investigator-blinded fashion. Ninety minutes of thoracic aortic occlusion was induced by a balloon catheter. During reperfusion, a goal-directed resuscitation protocol was performed. After 120 min of reperfusion, the anaesthetic regimen was changed to fentanyl–midazolam again for another 180 min. The oxygenation index and intra-pulmonary shunt fractions were calculated. After 5 h of reperfusion, a bronchoalveolar lavage was performed. The total protein content and lactate dehydrogenase activity were measured in epithelial lining fluid (ELF). Alveolar macrophage oxidative burst was analysed. The wet to dry ratio was calculated and tissue injury was graded using a semi-quantitative score. Ten animals (n=5 for each anaesthetic) without aortic occlusion served as time controls. Results: The oxygenation index decreased and the intra-pulmonary shunt fraction increased significantly in both occlusion groups. There were no significant differences between sevoflurane and propofol with respect to the oxygenation index, ELF composition, morphologic lung damage, wet to dry ratio and alveolar macrophage burst activity. Differences were, however, seen in terms of systemic haemodynamic stability, where catecholamine requirements were less pronounced with sevoflurane. Conclusion: We conclude that the severity of remote lung injury was not different between sevoflurane and propofol anaesthesia in this porcine model of severe lower-body ischaemia and reperfusion injury.

Therapy for severe myocardial ischemia/reperfusion sometimes necessitates intermittent positive pressure ventilation, which may impair left ventricular function by reduction of ventricular loading. It is unknown today whether positive airway pressure also affects contractile force after myocardial ischemia/reperfusion. The authors tested whether positive end-expiratory pressure (PEEP) impairs myocardial contractility in acute ischemic heart failure. In 11 anesthetized mechanically ventilated pigs (28 +/- 3 kg), cardiac output (CO, aortic flow probe), load-independent parameters of left ventricular contractility (conductance method: preload recruitable stroke work [PRSW] and end-systolic elastance [E(es)]) and preload (end-diastolic volume [EDV] conductance) were assessed before and after myocardial ischemia and reperfusion (left anterior descending artery occlusion, 60 min). Data were taken during PEEP 0, 5, and 10 cm H2O. Before myocardial ischemia, both PEEP 5 and 10 cm H2O reduced CO (P < 0.05) because of a reduction of EDV (P < 0.05, PEEP 10 cm H2O). The PRSW remained unchanged (not significant [NS]) and E(es) increased (P < 0.05, PEEP 10 cm H2O). After myocardial ischemia/reperfusion, CO and PRSW, but not E(es) (NS), deteriorated markedly. At the same time, PEEP 10 cm H2O reduced CO (P < 0.05) and, slightly, EDV (NS). Now, both PRSW (P < 0.05, PEEP 5 cm H2O) and E(es) (P < 0.05, PEEP 10 cm H2O) improved upon ventilation with PEEP. In our model, the administration of PEEP impaired global left ventricular function before and after myocardial ischemia/reperfusion. The observed impairment is not attributable to compromised contractility.

Near infrared spectroscopy scans of cerebral tissue in vivo were compared to reflectance pulse oximetry of local tissue by comparing each method to in vitro femoral arterial blood measurements in an experimental study on 16 newborn piglets. To test the accuracy, the 16 piglets were desaturated stepwise during general anaesthesia, leading to the following results of linear regression analysis of complete data, linear regression analysis for individual piglets and bias ± precision (1SD). Local oxygen saturation (reflectance pulse oximetry) versus arterial (haemoximeter): linear regression analysis R2 = 0.92, n = 207, linear regression analysis for individual piglets: R2 = 0.95 ± 0.05*, p < 0.05 versus near infrared spectroscopy, bias ± precision (1SD): 0.15 ± 9.65%; cerebral tissue oxygenation index (near infrared spectroscopy) versus arterial (haemoximeter): linear regression analysis R2 = 0.26, n = 161, linear regression analysis for individuals R2 = 0.83 ± 0.15, bias ± precision (1SD) −3.33 ± 29%; cerebral concentration of delta oxygenated haemoglobin (near infrared spectroscopy, NIRO 300) versus the corresponding arterial parameter (haemoximeter): linear regression analysis R2 = 0.76, n = 189, linear regression analysis for individuals R2 = 0.90 ± 0.06, bias ± precision (1SD) −2.54 ± 3 μM cm−3. The results of reflectance pulse oximetry in local tissue correlated more closely to in vitro femoral arterial blood measurements (haemoximeter) than results of near infrared spectroscopy, in vivo.

Objective: Intermittent positive pressure ventilation and positive end-expiratory pressure (PEEP) affect cardiac preload. Their effect is dependent on chest wall compliance. This study compares the effects of intermittent positive pressure ventilation and PEEP on stroke volume variation and central blood volume during open and closed chest conditions. Materials and methods: Fourteen anesthetized and mechanically ventilated pigs (25—40 kg) were studied. Central blood volume was assessed using global end-diastolic volume and right ventricular end-diastolic volume measured by thermodilution. Further, left and right ventricular stroke volume variations were determined with ultrasonic flow probes placedaroundthepulmonaryarteryandascendingaorta,respectively. Measurementswereperformedduringmechanicalventilationwithoutand with PEEP (15 cmH2O) in open and closed chest conditions. Results:With the chest closed mean arterial pressure, cardiac output, stroke volume, global end-diastolic volume, and right ventricular end-diastolic volume were significantly lower when compared to open chest conditions. Concomitantly, right ventricular, but not left ventricular stroke volume variation increased significantly. Applying PEEP led to a significant reduction of cardiac output, stroke volume and right ventricular end-diastolic volume, with a concomitant increase in left and right ventricular stroke volume variation both during open and closed chest conditions (all P-values < 0.05). Conclusions: We conclude that PEEP increases right and left ventricular stroke volume variation both during open and closed chest conditions. The concomitant reduction of right ventricular enddiastolic volume further indicates that PEEP has a preload reductive effect during open chest conditions, too.

The pre-ejection period (PEP) has recently been described as a potential parameter for monitoring cardiac preload. This study further investigated the influence of changes in intravascular volume status and the application of positive end-expiratory pressure (PEEP) on the pre-ejection period. In ten pigs, ECG, arterial pressure and stroke volume derived from an aortic flowprobe were registered. Global end-diastolic volume (GEDV) was measured by transcardiopulmonary thermodilution. Total blood volume (TBV) and intrathoracic blood volume (ITBV) were measured by the dye-dilution technique. Measurements were performed during normovolaemic conditions, after volume loading with haemodilution blood (20 ml kg(-1)) and following haemorrhage (30 ml kg(-1)) without PEEP and with PEEP (15 cm H(2)O) applied. Volume loading increased GEDV, ITBV, TBV and SV, whereas PEP remained constant. However, the changes were not significant (P0.05). Subsequent haemorrhage significantly decreased GEDV (from 436 to 308 ml), ITBV (from 729 to 452 ml), TBV (from 2,131 to 1,488 ml) (all P-values0.05), and SV (from 20.7 ml to 14.3 ml, P0.001). However, PEP did not change significantly (from 73 to 82 ms, P0.05). No correlation between the changes in PEP and changes in any other variable was observed. It is concluded that PEP is not sensitive to the changes in intravascular volume status.

Inhaled prostacyclin (PGI2) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular (RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI2 analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng·kg–1·min–1) and, consecutively, ILO (60 ng·kg–1·min–1) for 20 min each. We measured pulmonary artery pressure (PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, Ees). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. Ees was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI2 aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function.

Background Acute normovolemic hemodilution reduces the circulating erythrocyte mass and, thus, the hemoglobin concentration. After extreme acute normovolemic hemodilution to the critical hemoglobin concentration (Hbcrit), oxygen demand of the tissues is no longer met by oxygen supply, and death occurs with increasing oxygen debt. The aim of the current study was to investigate whether ventilation with 100% oxygen (fraction of inspired oxygen [FiO2] = 1.0; hyperoxic ventilation) initiated at Hbcrit could restore adequate tissue oxygenation and prevent death. Methods Fourteen anesthetized pigs ventilated with room air (FiO2 = 0.21) were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual Hbcrit was reached. Hbcrit was defined as the onset of oxygen supply dependency of oxygen consumption and was identified with indirect calorimetry. For the next 6 h, animals were either ventilated with an FiO2 of 0.21 (n = 7) or an FiO2 of 1.0 (n = 7). Results All animals in the 0.21 FiO2 group died within the first 3 h at Hbcrit (i.e., 6-h mortality 100%). Death was preceded by an increase of serum concentrations of lactate and catecholamines. In contrast to that, six of the seven animals of the 1.0 FiO2 group survived the complete 6-h observation period without lactacidosis and increased serum catecholamines (i.e., 6-h mortality 14%; FiO2 0.21 vs. FiO2 1.0, P < or = 0.05). After 6 h at Hbcrit, the FiO2 was reduced from 1.0 to 0.21, and five of the six animals died within the next 3 h. Conclusion In anesthetized pigs submitted to lethal anemia, hyperoxic ventilation enabled survival for 6 h without signs of circulatory failure.

We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n = 12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs.

Summary Objective: The onset of hyperoxic ventilation after hemodilution to the critical hematocrit (Hctcrit) improves myocardial and peripheral tissue oxygenation. However, it is unknown whether at Hctcrit hyperoxemia is also beneficial to intestinal oxygenation, since intestinal tissue hypoxia might even worsen as a result of hyperoxic vasoconstriction. To study this, we investigated whether hyperoxic ventilation started at Hctcrit is beneficial in terms of intestinal oxygenation. Method: 18 anesthetized pigs were hemodiluted to their individual Hctcrit (onset of myocardial ischemia; ECG) by 1:1 exchange of blood with 6% pentastarch (200,000/0.5). At Hctcrit hyperoxic ventilation was initiated. Nine complete datasets were obtained and analyzed at baseline, at Hctcrit and during hyperoxic ventilation. Analysis included intestinal O2 transport parameters (portal blood gases), intestinal mucosal O2 partial pressure (MDO-Electrode) and regional intestinal blood flow (microsphere method). Results: At Hctcrit (7.2 ±1.2%), intestinal O2 delivery was reduced. Despite increased O2 extraction, local tissue hypoxia was documented by markedly reduced portal venous (26 ± 2 Torr) and jejunal O2 (9 ± 3 Torr) partial pressures. Portal venous base excess (-10 ± 3 mmol/L) and lactate concentration (4.3 ± 1.4 mmol/L) evidenced anaerobic intestinal metabolism (all p < 0.05). During hyperoxic ventilation, intestinal O2 delivery increased (p < 0.05) requiring a less intensive O2 extraction; physically dissolved O2 extracted from plasma was predominantly responsible for the restoration of portal and intestinal mucosal O2 partial pressure (49 ± 2 Torr and 17 ± 4 Torr; p < 0.05 vs. Hctcrit). Portal base excess (-12 ± 6 mmol/L) and lactate concentration (4.3 ± 1.9 mmol/L) did not recover. Conclusion: Hyperoxic ventilation at Hctcrit did improve intestinal O2 transport and mucosal oxygenation after 15 min. However, intestinal O2 debt persisted during the observation time. Summary Hyperoxic ventilation reverses manifest intestinal mucosal tissue hypoxia at Hctcrit due to the efficacious utilization of physically dissolved O2. There is no evidence that at Hctcrit hyperoxia-induced vasoconstriction further does impair microvascular intestinal blood flow and O2 transport. It remains unclear, to which extent hyperoxic ventilation may induce relevant O2 shunts. Hence, the true value of this technique for a possible use in humans remains to be elucidated.

Although inhaled nitric oxide (NO i ) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO i have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO i in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO i increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO i in the cerebral vasculature, which may occur preferentially in the venous compartment.

Objective: During normovolaemic haemodilution arterial O2-content decreases exponentially. Nevertheless, tissue oxygenation is first maintained initially by increased organ perfusion and O2-extraction. As soon as these compensatory mechanisms are exhausted, myocardial ischaemia and tissue hypoxia occur at an individual ‘critical’ haematocrit (Hct) value. This study was conducted in order to assess whether tissue hypoxia at the critical Hct is reversed by hyperoxic ventilation with 100% O2. Method: Eighteen anaesthetized pigs were ventilated with room air and were hemodiluted by 1:1 exchange of blood with 6% pentastarch to their individual critical Hct (onset of myocardial ischaemia; significant ECG changes). At the critical Hct, hyperoxic ventilation was initiated. In nine complete datasets, global O2 delivery and consumption, local tissue O2 partial pressure (tpO2) (MDO-Electrode, Eschweiler, Kiel, Germany) and organ blood flow (microsphere method) in skeletal muscle were analyzed at baseline, after haemodilution to the critical Hct and after 15 min of hyperoxic ventilation. Results: At the critical Hct (7.2±1.2%), tpO2 was reduced from 23±3 to 10±2 Torr with 50% of all values in the hypoxic range (

Background: The blood volume that has to be exchanged for crystalloids and/or colloids during acute normovolemic hemodilution (ANH) in order to reach a preset target hemoglobin concentration (hb) is usually predicted by the Bourke and Smith formula developed in 1974. This formula systematically overestimates the ‘true’ exchangeable blood volume (EBV), a fact that may potentially endanger patients because the target hb will be missed and the normovolemic anemia might turn out to be more severe than a priori intended. Our objective was to develop a more accurate mathematical model of hemodilution kinetics and to validate this new model in animals and in patients undergoing ANH. Methods: Twenty-two anesthetized beagle dogs and 18 patients under balanced anesthesia underwent isovolemic hemodilution with hydroxyethyl starch (HAES 6%, 200 000) to a target hb of 7 g dl−1 or 9 g dl−1, respectively. Exchangeable blood volume predicted by use of the different mathematical models was compared with the blood volume actually exchanged to meet the preset target hb. Results: Calculation of EBV by the Bourke and Smith formula (EBVB + S) systematically overestimated the volume actually exchanged (overestimation: dogs 15%, patients 20%), whereas our new iterative model predicted EBV (EBViterative) more reliably (overestimation: dogs 1%, patients 8%). In both cases EBVB + S differed significantly from the EBViterative. Conclusion: Exchangeable blood volume is predicted more accurately by the new iterative model than by the Bourke and Smith formula. The iterative model leads to an improvement in patient safety and provides a physiologically adequate basis for future studies investigating the efficacy of ANH in reducing allogenic blood transfusions.

Background: Gastric tonometry is intended to reveal alterations in splanchnic perfusion and oxygenation. Based on the tonometric measurement of gastric mucosal partial pressure of carbon dioxide (pCO2) and the simultaneous determination of arterial blood gas parameters (bicarbonate concentration [HCO3–], pH and pCO2), several parameters can be calculated. Aims: To identify the most suitable tonometric parameter [gastric mucosal pH (pHi), intramucosal pCO2 (piCO2), the difference between tonometric and arterial pCO2 concentrations (pCO2 gap), [H+] gap] that reliably reflects gastric hypoperfusion and hypoxia during severe haemorrhagic shock. Design: Randomised, controlled experimental study. Methods: An artificial stenosis of the left anterior descending coronary artery (LAD) was induced. Subsequently, the animals were haemorrhaged to a mean arterial pressure of 45 mmHg, which was maintained for 60 min. Measurements and main results: Tonometric measurements were performed in 17 land-race pigs before and after induction of LAD stenosis and after haemorrhagic shock. P values obtained using the Wilcoxon signed-rank testing were used to compare the level of significance for the tonometric parameters and the corresponding arterial blood gas values [arterial pCO2 (paCO2), [HCO3–], arterial pH (pHa)]. While induction of critical coronary stenosis did not provoke any changes, all parameters changed significantly during haemorrhagic shock. The lowest P value was found for pHi (P=0.00013) followed by [H+ gap] (P=0.0005). P values higher by a factor of ten were found for pCO2 gap (P=0.00119) and were highest for piCO2 (P=0.00562). P values of the corresponding arterial blood gas parameters were lower by a factor of ten than the P value of piCO2. Conclusion: pHi, pCO2 gap and [H+] gap are considerably influenced by changes of systemic arterial blood gas values. This is demonstrated by lower P values of the corresponding arterial blood gas values in comparison with piCO2. Therefore pHi, pCO2 gap and [H+] gap seem to indicate more likely systemic changes, whereas piCO2 appears to reflect disturbances of regional gastric tissue perfusion and oxygenation more reliably than any other derived tonometric parameter.

The heterogeneity of regional pulmonary blood flow (RPBF) can be assessed by fractal analysis. The fractal dimension (FD) is a scale-independent measure of spatial heterogeneity of blood flow. The relative dispersion (RD) is often used to obtain the heterogeneity of RPBF but it is influenced by the resolution of measurement. The Blood Flow Analysis (BFA) System was developed in Delphi to represent the three-dimensional structure of lung blood flow and calculates statistics of FD, RD, spatial correlation of neighbored tissue samples and shows histograms of blood flows at diverse time points during different experiments. The BFA System reads a text file with flows, measured with fluorescent microsphere technique, and constructs the lung anatomy with volumetric pixels showing the flows with a color schema. It is possible to rotate the lungs into two axis (XY) and the statistics are shown with 3D graphics. The System maintains a database with data from various studies at same time. The BFA System was validated with four data sets from previous experiments. The BFA System has shown consistency and it is a new tool to help researchers during lung perfusion studies.

Ischamiebedingte Veranderungen der linksventrikularen (LV) Relaxationseigenschaften gehen haufig entsprechenden EKG-Veranderungen voraus. Im Rahmen der vorliegenden tierexperimentellen Untersuchung sollte geklart werden, ob eine durch akute normovolamische Hamodilution (ANH) induzierte Verdunnungsanamie (Hamatokrit, HKT, 20%) mit Veranderungen der diastolischen LV-Funktion einhergeht. Bei Raumluftbeatmung wurde 22 narkotisierten, splenektomierten Beagle-Zuchthunden so lange Vollblut entzogen und simultan durch isoonkotische Hydroxyathylstarke (6% HAS 200.000/0,5) ersetzt, bis ein HKT-Wert von 20% erreicht war. Vor und nach ANH wurden das intravasale Blutvolumen (Indozyaningrun-Verdunnungsmethode), die regionale Myokardperfusion (radioaktive Mikrospharentechnik) sowie folgende Parameter der LV-Diastolenfunktion mittels kontinuierlicher LV-Katheterisierung bestimmt: 1) die maximale Druckabfallsgeschwindigkeit im linken Ventrikel, LV dp/dtmin, 2) die Beziehung zwischen LV-Druck und Volumen zum Zeitpunkt der Enddiastole bei unterschiedlicher LV-Vorlast (enddiastolic pressure volume relationship – EDPVR; Conductance-Methode) und 3) die Relaxationszeitkonstante “τ” des LV-Myokards. Die diastolische LV-Funktion anderte sich nach ANH auf HKT 20% in unserem Modell nicht. Insbesondere die lastunabhangigen Parameter (EDPVR-Steigung und τ) waren nach ANH unverandert. Die Abnahme von dp/dt min (−2724±479 vs. −2388±408 mmHg·s−1; p

Hemorrhagic shock alters heterogeneity of regional myocardial perfusion (RMP) in the presence of critical coronary stenosis in pigs. Conventional resuscitation has failed to reverse these effects. We hypothesized that improvement of the resuscitation regime would lead to restoration of RMP heterogeneity. Diaspirin-cross-linked hemoglobin (10 g/dl; DCLHb) and human serum albumin (8.0 g/dl; HSA) were used. After baseline, a branch of the left coronary artery was stenosed; thereafter, hemorrhagic shock was induced. Resuscitation was performed with either DCLHb or HSA. At baseline, the fractcal dimension ( D) of subendocardial myocardium was 1.31 ± 0.083 (HSA) and 1.35 ± 0.106 (DCLHb) (mean ± SD). Coronary stenosis increased subendocardial D slightly but consistently only in the DCLHb group (1.39 ± 0.104; P < 0.05). Shock reduced subendocardial D: 1.21 ± 0.093 (HSA; P = 0.10), 1.25 ± 0.092 (DCLHb; P < 0.05). Administration of DCLHb increased subendocardial D in 7 of 10 animals (1.31 ± 0.097; P = 0.066). HSA was ineffective in this respect. DCLHb infusion restored arterial pressure and increased cardiac index (CI) to 80% of baseline values. Administration of HSA left animals hypotensive (69 mmHg) and increased CI to 122% of the average baseline value. Shock-induced disturbances of the distribution of RMP were improved by administration of DCLHb but not by HSA.

Objective: Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantion. Design: Prospective clinical dose- response study. Setting: Anesthesiological intensive care unit of a university hospital. Patients and participants: 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2) of less than 13.3 kPa (100 mmHg). Interventions: Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. Measurements and results: Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p < 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO2 increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO2), all were subject to long-term inhalation (1–19 days). All were successfully weaned from NO and were discharged from the intensive care unit. Conclusion: The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation.

Kleen, Martin, Martin Welte, Peter Lackermeier, Oliver Habler, Gregor Kemming, and Konrad Messmer. Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis. J. Appl. Physiol.83(6): 1832–1841, 1997.—We analyzed the effects of shock and small-volume resuscitation in the presence of coronary stenosis on fractal dimension ( D) and spatial correlation (SC) of regional myocardial perfusion. Hemorrhagic shock was induced and maintained for 1 h. Pigs were resuscitated with hypertonic saline-dextran 60 [HSDex, 10% of shed blood volume (SBV)] or normal saline (NS; 80% of SBV). Therapy was continued after 30 min with dextran (10% SBV). At baseline, D was 1.39 ± 0.06 (mean ± SE; HSDex group) and 1.34 ± 0.04 (NS group). SC was 0.26 ± 0.07 (HSDex) and 0.26 ± 0.04 (NS). Left anterior descending coronary artery stenosis changed neither D nor SC. Shock significantly reduced D(i.e., homogenized perfusion): 1.26 ± 0.06 (HSDex) and 1.23 ± 0.05 (NS). SC was increased: 0.41 ± 0.1 (HSDex) and 0.48 ± 0.07 (NS). Fluid therapy with HSDex further decreased D to 1.22 ± 0.05, whereas NS did not change D. SC was increased by both HSDex (0.56 ± 0.1) and NS (0.53 ± 0.06). At 1 h after resuscitation, SC was constant in both groups, and D was reduced only in the NS group (1.18 ± 0.02). We conclude that hemorrhagic shock homogenized regional myocardial perfusion in coronary stenosis and that fluid therapy failed to restore this.

Inhalation of nitric oxide (NO) and prostacyclin (PGI2) may induce selective pulmonary vasodilation and-by improving ventilation-perfusion ratio in ventilated areas of the lung-increase Pao2 in patients with acute lung injury. To assess the therapeutic efficacy of both compounds, dose-response curves were established in patients with adult respiratory distress syndrome (ARDS). Patients received both PGI2 (doses of 1, 10, and 25 ng/kg/min) and NO (concentrations of 1, 4, and 8 ppm). Cardiorespiratory parameters were assessed at control, at each drug concentration, and after withdrawal of NO and PGI2. PGI2 resulted in a significant, dose-dependent and selective reduction of pulmonary artery pressure (PAP) from 35.1 +/- 6.3 mm Hg at control to 33.1 +/- 4.8 (1 ng/kg/min), 31.3 +/- 4.8 mm Hg (10 ng/kg/min) and 29.6 +/- 4.5 mm Hg (25 ng/kg/min), respectively. Inhaled NO reduced PAP from 34.5 +/- 5.6 to 32.1 +/- 5.9 mm Hg at 4 ppm, and to 31.8 +/- 6.1 mm Hg at 8 ppm, respectively, with no effect at 1 ppm. Pao2/Flo2 ratio increased from 105 +/- 37 to 125 +/- 56 mm Hg (range of increase: 0 to 57 mm Hg) at PGI2 10 ng/kg/min and to 131 +/- 63 mm Hg (range: -5 to 89 mm Hg) at 25 ng/kg/min with no effect at 1 ng/kg/min. NO improved Pao2 (e.g., from 116 +/- 47 to 167 +/- 86 mm Hg at 8 ppm) and reduced intrapulmonary shunt at all doses tested. We conclude that both inhaled PGI2 and NO may induce selective pulmonary vasodilation and increase Pao2 in severe ARDS.

The influence of severe acute normovolemic hemodilution (ANH) on myocardial contractility (MC) was investigated in 14 splenectomized, anesthetized dogs. MC was assessed by the maximum rate of left ventricular pressure increase (LVdp/dt(max)), end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) (conductance catheter, left ventricular pressure-volume relationship). Measurements of myocardial perfusion and oxygenation (radioactive microsphere technique) assured comparability of the model to previously performed studies. Global and regional myocardial blood flow increased significantly upon hemodilution with preference to midmyocardium and subendocardium. This resulted in preservation of both myocardial oxygen delivery and consumption after ANH. Myocardial oxygen extraction as well as coronary venous Po2 were unaffected by ANH, while coronary venous lactate concentration decreased, indicating that myocardial oxygen need was met. LVdp/dt(max) decreased significantly after hemodilution (2278 +/- 577 vs 1884 +/- 381 mm Hg/s, P < 0.01), whereas Ees and PRSW increased significantly (1.76 +/- 0.54 vs 2.15 +/- 0.75 mm Hg/mL, P < 0.05, for Ees and 33 +/- 14 vs 45 +/- 14 mm Hg.mL, P < 0.05, for PRSW). While the decrease of LVdp/dt(max) most likely reflects ANH-induced changes of ventricular pre- and afterload, the increase of Ees and PRSW indicates a true increase of myocardial contractility during ANH in anesthetized dogs.

BACKGROUND AND OBJECTIVE Systemically administered lidocaine has been shown to have anti-inflammatory properties. Inhalation is an attractive way of application because of high pulmonary compound concentrations and potentially fewer systemic side effects. The aim of this study was to clarify whether inhaled or, likewise, intravenous lidocaine can attenuate the inflammatory response in a model of experimental endotoxaemia in the rat. METHODS Animals randomly received (nine animals in each group) lidocaine, either aerosolized 4 mg kg(-1) (Lid(Ae4.0)) and 0.4 mg kg(-1) (Lid(Ae0.4)) or 4 mg kg(-1) intravenously (Lid(iv)) before intravenous injection of 5 mg kg(-1) lipopolysaccharide (LPS). Administration of lidocaine was repeated after 2 h. Additional control animals were observed either without (sham) or with the infusion of LPS. Following 5 h of experimental endotoxaemia, the concentrations of tumour necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta) and IL-6 were measured in bronchoalveolar lavage fluid and blood plasma. Release of nitrite in ex-vivo cultured alveolar macrophages was measured by Griess assay. RESULTS Bronchoalveolar lavage fluid levels of IL-1beta and TNFalpha in Lid(Ae4.0) (IL-1beta, -47%; TNFalpha, -41%; P < 0.05) and Lid(iv) (IL-1beta, -55%; TNFalpha, -54%; P < 0.05) but not in Lid(Ae0.4) were significantly lower than in LPS. Plasma cytokine levels were not attenuated. Nitrite was found to be significantly reduced in Lid(Ae4.0) (-46%), Lid(Ae0.4) (-39%) and Lid(iv) (-41%) when compared with LPS (P < 0.05, respectively). CONCLUSION Pretreatment of endotoxaemic rats either with Lid(Ae4.0) or with Lid(iv) attenuated the levels of proinflammatory mediators in bronchoalveolar lavage fluid. Plasma cytokine levels were not affected. Nebulized lidocaine (0.4 mg kg(-1)) inhibited the nitrite release but did not affect the cytokine levels.

Thoraco-abdominal-aneurysm surgery predicts high mortality. Propofol and sevoflurane are commonly used anaesthetics for this procedure. Halogenated anaesthetics induce organ protection similar to ischaemic preconditioning. We investigated which anaesthetic regimen would lead to a better protection against ischaemia-reperfusion injury induced by temporary thoracic-aortic occlusion.Following initial fentanyl-midazolam anaesthesia for surgical preparation, 18 pigs were randomly assigned to two groups: group one received propofol (n=9) and group two sevoflurane (n=9) before, during, and after lower body ischaemia in an investigator blinded fashion. Ten animals without aortic occlusion served as time controls (propofol, n=5; sevoflurane, n=5). For induction of ischaemia, the thoracic aorta was occluded by a balloon-catheter for 90 min. After 120 min of reperfusion, the study anaesthetics were discontinued and fentanyl-midazolam re-established for an additional 180 min. Goal-directed therapy was performed during reperfusion. Fluid and catecholamine requirements were assessed. Serum samples and intestinal tissue specimens were obtained.Severe declamping shock occurred in both study groups. While norepinephrine requirements in the sevoflurane group were significantly reduced during reperfusion (P0.05), allowing cessation of catecholamine support in 4/9 animals, all 9/9 animals were still catecholamine dependent at the end of the experiment in the propofol group. Serum activities of lactate dehydrogenase, aspartate transaminase, and alanine aminotransferase were lower with sevoflurane (P0.05). Small intestine tissue specimens did not differ histologically.Use of sevoflurane compared with propofol attenuated the haemodynamic sequelae of reperfusion injury in our model. Release of serum markers of cellular injury was also attenuated.

Perfluorocarbon (PFC) emulsions are intravascular oxygen therapeutics that temporarily enhance tissue oxygenation in dilutional anemia. However, PFC emulsions are not resuscitation fluids because PFCs only work optimally in the presence of high O 2 partial pressure (hyperoxia); moreover, because they have no oncotic potential, dosing limitations prevent their use to permanently replace large hemorrhage volumes. Our objective was to clarify whether in the presence of hyperoxia a conventional colloid therapy supplemented by PFC is more efficacious than colloid alone. To answer this question, 22 anesthetized, ventilated dogs were hemorrhaged to a mean arterial pressure of 45 mmHg and were kept at this level until a metabolic O 2 debt of 120 mL kg -1 body weight had evolved. Hyperoxia was established and dogs were randomly allocated to receive colloid (6% HES, Hydroxy Ethyl Starch shed blood volume) or colloid together with Oxygent (perflubron emulsion, 60%, w/v; Alliance Pharmaceutical Corp., San Diego, CA; single dose, 4.5 mL kg -1 ; i.e., 2.7 g PFC kg -1 body weight) in a blinded fashion. Hemodynamic and O 2 transport parameters, intestinal mucosal blood flow (microspheres), and O 2 partial pressure (MDO-Electrode; Eschweiler, Kiel, Germany) were measured at baseline, in shock, and during 3 h post-therapy. In the presence of hyperoxia, Oxygent improved the amount of physically dissolved O 2 in plasma and increased the contribution of physically dissolved O 2 to global O 2 delivery (P < 0.05) and thus whole body O 2 consumption when compared with colloid alone (P< 0.05). As a result, Oxygent reduced intestinal mucosal hypoxia and global O 2 debt within the first hour post-therapy (P < 0.05). We conclude that under hyperoxic conditions, fluid resuscitation supplemented by Oxygent was more efficacious than colloid and hyperoxia alone. PFC temporarily enhanced intestinal mucosal tissue oxygenation during resuscitation.

Background Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs. Methods Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg.kg . h for 1 h and 10 microg.kg.h for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n=7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion. Results After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin). Conclusions Inhalation of vaporized perfluorohexan does not improve pulmonary gas exchange or respiratory compliance in endotoxin-induced porcine lung injury.

Summary Background: Ventilation with pure oxygen (hyperoxic ventilation, HV) increases arterial oxygen content (CaO2). However HV induces arteriolar constriction and thus potentially affects O2 supply. We therefore investigated the effects of HV on regional blood flow (RBF) and O2 supply of different vital organs during moderate normovolaemic anaemia. Methods: Twenty-two anaesthetized dogs were haemodiluted under normoxia (i.e. FiO2 = 0·21) to a target haemoglobin concentration (Hb) of 7 g dl−1 and were subsequently ventilated with pure O2. RBF was determined by use of the radioactive microspheres method in the myocardium, kidney, skeletal muscle, liver, intestine, stomach, and pancreas at Hb = 7 g dl−1 and after subsequent initiation of HV. RBF in proportion to cardiac output (RBFrelative), the variation coefficient of RBF (VC) and regional O2 supply (rDO2) were calculated. Results: Initiation of HV at Hb = 7·0 ± 0·3 g dl−1 reduced cardiac index (−17%) as well as RBF within the myocardium (−21%), pancreas (−25%), and skeletal muscle (−25%), whereas renal, hepatic, and intestinal RBF remained unchanged. Consequently RBFrelative of the latter organs increased. Heterogeneity of RBF was marginally affected by HV. Conclusion: The initiation of HV during moderate normovolaemic anaemia (Hb =7 g dl−1) was accompanied by RBF redistribution with preference for renal, hepatic and intestinal O2 supply. Cardiac, pancreatic and muscular O2 supply decreased, however without any critical restriction of organ function.

Background: Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas. Methods: In 20 anesthetized domestic pigs with an experimentally induced coronary stenosis, shock (mean arterial pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). Completion of resuscitation was followed by a 60-min observation period. Regional blood flow to the kidneys and the pancreas was measured by use of the radioactive microspheres method at baseline, after shock and 60 min after fluid resuscitation. Results: All animals (10/10) resuscitated with DCLHb survived the 60-min observation period, while 5/10 control animals died within 20 min due to persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and kidneys of DCLHb-treated animals revealed lower total and regional organ perfusion and regional oxygen delivery. Renal and pancreatic blood flow heterogeneity was higher in the DCLHb group. Conclusion: DCLHb-induced vasoconstriction afforded superior myocardial perfusion, but impaired regional perfusion of the kidneys and the pancreas.

The prostaglandin I2 analogues epoprostenol and iloprost increase left ventricular contractility. Therefore, we hypothesize that the prostaglandin I2 analogues epoprostenol and iloprost improve also left ventricular diastolic function. To test this hypothesis, the effects of epoprostenol and iloprost on left ventricular diastolic function were assessed in vivo and compared to two vasodilators sodium nitroprusside and adenosine, not formerly associated with changes of left ventricular contractility. Eleven pigs (25.9+/-2.8 kg, balanced anaesthesia) were exposed to the short-acting intravenous vasodilators sodium nitroprusside, adenosine and epoprostenol in a randomized cross over design. The long-acting iloprost was administered at the end of the protocol. The drugs are titrated to achieve a 25% reduction of diastolic aortic pressure. Active isovolumic relaxation properties of the left ventricle were assessed by the maximum velocity of left ventricular pressure drop. Passive phase of relaxation and filling was assessed by the determination of end diastolic compliance during a preload reduction manoeuvre. The maximum velocity of left ventricular pressure drop worsened during the infusion of sodium nitroprusside (baseline: -1950; sodium nitroprusside: -1293 mm Hg/s, p0.05, Wilcoxon signed rank test versus vs. baseline) and adenosine (baseline: -2015; adenosine: -1345 mm Hg/s, p0.05), but remained stable during the infusion of the prostaglandins (baseline: -1943; epoprostenol: -1785 mm Hg/s; baseline: -2042; iloprost: -1923 mm Hg/s). End diastolic compliance was not altered significantly by any vasodilator. Interstitial myocardial cAMP increased during the infusion of epoprostenol (7.60 to 13.87 fmol/ml, p0.05) and tended to increase during the infusion of iloprost (7.56 to 11.66 fmol/ml, p=0.21). The prostaglandin I(2) analogues epoprostenol and iloprost preserved the early phase of active isovolumic relaxation, presumably mediated by myocardial cAMP, whereas sodium nitroprusside and adenosine impaired early active isovolumic relaxation. Passive relaxation and filling properties remained stable during the infusion of each applied vasodilator in the intact left ventricle in vivo.

The authors have adjusted a jet nebulizer to a mechanical ventilator (Servo Ventilator, Siemens) to deliver an aerosol to rats. They aimed to clarify whether a modified jet nebulizer generating particles with a mass median aerodynamic diameter of 2 microm would be effective and safe in intubated ventilated rats. Fluorescent microspheres (diameter: 1.0 microm) were aerosolized to verify qualitatively and quantitatively intrapulmonary deposition. Particle deposition fraction was 3.8% (1.3%) of the delivered dose (median [interquartile range]). There was no evidence for any adverse event as assessed from heart rate, mean arterial pressure, PaO2 and PaCO2 before, during, and after nebulization. No pulmonary tissue trauma was detected histologically.

Background: Hemodilution reduces hematocrit (Hct) and blood oxygen content. Tissue oxygenation is mainly preserved by increased cardiac output. As myocardial O2-demands increase, coronary vasodilatation becomes necessary to increase myocardial blood flow. Myocardial ischemia occurs at a critical Hct-value (Hctcrit), with accompanying exhaustion of coronary reserve. Hyperoxic ventilation is known to both reverse peripheral tissue hypoxia at Hctcrit and also to induce coronary vasoconstriction. This study aimed to determine whether hyperoxic ventilation at Hctcrit further exacerbates myocardial ischemia and dysfunction. Methods: Nine anesthetized pigs ventilated on room air were hemodiluted by 1 : 1 exchange of blood with pentastarch (6%HES) to Hctcrit , defined as onset of myocardial ischemia (ECG changes). At Hctcrit , hyperoxic ventilation was started. Measurements were performed at baseline, at Hctcrit, and after 15 min of hyperoxic ventilation. We determined myocardial blood flow (microsphere method), arterial O2-content, subendocardial O2-delivery and myocardial function (left ventricular pressure increase). Results: At Hctcrit 7 (6;8)%, O2-content was reduced [3.7 (3.1;3.9) ml dl−1]. Despite a compensatory increase of myocardial blood flow [531 (449;573), ml min−1100 g−1], all pigs displayed myocardial ischemia and compromised myocardial function (P

Ventilation with 100% oxygen (Fio(2) 1.0; hyperoxic ventilation; HV) as an alternative to red blood cell transfusion enables survival in otherwise lethal normovolemic anemia. The aim of the present study was to investigate whether HV as a supplement to fluid infusion therapy could also restore adequate tissue oxygenation and prevent death in otherwise lethal hemorrhagic shock. In 14 anesthetized pigs ventilated on room air (Fio(2) 0.21), hemorrhagic shock was induced by controlled withdrawal of blood (target mean arterial pressure 35-40 mmHg) and maintained for 1 h. Subsequently, the animals were partially fluid-resuscitated (i.e., replacement of lost plasma volume) either with hydroxyethyl starch (6% HES, 200/0.5) alone (G 0.21) or with HES supplemented by HV (G 1.0). After completion of partial fluid resuscitation, all animals were followed up for the next 6 h. Five of seven animals of G 0.21 died within the 6-h observation period (i.e., 6-h mortality 71%). Death was preceded by a continuous increase of the serum concentrations of arterial lactate and persistent tissue hypoxia. In contrast to that, all animals of G 1.0 survived the 6-h observation period without lactic acidosis and with improved tissue oxygenation (i.e., 6-h mortality 0%; G 0.21 versus G 1.0 P < 0.05). In anesthetized pigs submitted to lethal hemorrhagic shock, the supplementation of partial fluid resuscitation with HV improved tissue oxygenation and enabled survival for 6 h.

Reperfusion triggers the expression of inflammatory cytokines and adhesion molecules that increase the rate of apoptosis in the reperfused tissues after ischaemia, thus worsening the outcome of the grafts. Polyclonal anti-thymocyte globulins (pATGs) are able to reduce the number of lymphocytes as well as block adhesion molecules and induce apoptosis in T-lymphocytes through Fas-ligand. The aims of this study were to investigate the influence of pATGs on the prevention of apoptosis of reperfused tissues after ischaemia and to monitor their capability to enhance lymphocyte apoptosis thus decreasing the deleterious effects of ischaemia/reperfusion injury (IRI). Extremities of cynomolgus monkeys ( n=8) were flushed via either the femoral or the brachial artery. After 60 min of ischaemia the limbs were reperfused with human blood. ATG was added to the blood in a therapeutic dose 20 min prior to reperfusion of the extremities. Surgically available limbs ( n=20) were assigned to the following groups: ATG group ( n=10) and control group (without ATG; n=10). DNA fragmentation analysis was performed in situ to detect apoptosis at the single-cell level. Our study shows an increased rate of muscle and connective tissue apoptosis in the control group compared with the ATG-treated group. Cells found in the vascular areas present different rates of apoptosis, with enhanced cellular death of endothelium and connective perivascular areas being observed in the control group. The group treated with ATG shows an increased rate of white blood cell (WBC) apoptosis in vascular and perivascular areas. Previous studies have shown that pATGs are able to induce apoptosis as well as complement-mediated cell death in peripheral T-lymphocytes in vitro. Our results confirm that pATGs not only increase the rate of apoptosis of WBCs in vivo but also have a protective effect on the reperfused tissue. This may alleviate the damage after reperfusion of solid-organ transplantation.

The principal effects of prostaglandin I2 are vasodilation and inhibition of platelet aggregation induced by a rise in the intracellular second messenger cAMP. In the heart a rise in intracellular myocardial cAMP increases contractility. We examined whether prostaglandin I2 increases left ventricular contractility in vivo. The effects of epoprostenol and iloprost on left ventricular contractility were assessed in vivo and compared to the effects of adenosine and sodium nitroprusside, which exerts vasodilatory properties independently of cAMP. Prospective, randomized, cross-over in a university laboratory. Eleven pigs (25.9±2.8 kg, balanced anesthesia). Each animal was exposed to intravenous sodium nitroprusside, adenosine, and epoprostenol in randomized order. Iloprost was administered at the end due to its longer half-life. The dose was titrated to achieve a 25% reduction in diastolic aortic pressure. Left ventricular contractility was assessed before, during, and after each intervention by determination of the endsystolic elastance with the conductance method. While there was no change in endsystolic elastance upon the infusion of adenosine and sodium nitroprusside; endsystolic elastance increased in the case of epoprostenol (57%) and iloprost (71%) . Left ventricular contractility is increased in vivo by epoprostenol and iloprost but not by adenosine or sodium nitroprusside at equipotent hypotensive dose. A contribution of sympathetic reflex activation of cardiac nerves on the increase in left ventricular contractility cannot be completely ruled out.

Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba [1]and Frostell in 1991 [2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator [3]while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO’s potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators – the prostanoids – came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is – among a lot of other valuable work – based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer [4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed.

Intraoperative surgical blood loss is initially replaced by infusion of red cell-free, cristalloidal or colloidal solutions. When normovolemia is maintained the ensuing dilutional anemia is compensated by an increase of cardiac output and of arterial oxygen extraction. In the ideal case, a surgical blood loss can entirely be ‘bridged’ without transfusion by intraoperative normovolemic hemodilution. However major blood loss results in extreme hemodilution and the transfusion of red blood cells may finally become necessary to increase arterial oxygen content and to preserve tissue oxygenation. When transfusion has to be started before surgical control of bleeding has been achieved, parts of the red blood cells transfused will get lost, thereby increasing intraoperative transfusion needs. Beside red blood cell transfusion, arterial oxygen content can be rapidly increased by ventilating the patient with 100% oxygen (hyperoxic ventilation), thus enhancing the amount of physically dissolved oxygen in plasma (hyperoxia). In experimental and clinical studies hyperoxic ventilation has emerged as a simple, safe and effective intervention to enlarge the margin of safety for hemodynamic compensation and tissue oxygenation in hemodiluted subjects experiencing major bleeding. The hyperoxia-associated microcirculatory dysregulation and impaired tissue oxygenation known to take place in the presence of a physiologic hemoglobin concentration are not encountered in hemodiluted subjects. Hyperoxic hemodilution i.e. the combination of intraoperative extreme hemodilution and hyperoxic ventilation may therefore be considered a cost-effective, safe and efficient supplement to reduce allogeneic transfusion during surgical interventions associated with high blood losses. The vast majority of the experimental and clinical investigations this new concept is based on was initiated and performed under the guidance of Prof. Konrad Messmer.

In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O2 content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dtmin) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (τ) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.

Normovolemic hemodilution is an effective strategy to limit perioperative homologous blood transfusions. The reduction of hematocrit related to hemodilution results in reduced arterial oxygen content, which initially is compensated for by an increase in cardiac output and oxygen extraction ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and tissue hypoxia.To assess whether hemodilution can be extended to lower hematocrit values by the use of a hemoglobin-based artificial oxygen carrier solution.Prospective, randomized, controlled.Animal laboratory of a university hospital.Twelve anesthetized, mechanically ventilated pigs.Isovolemic hemodilution was performed with either 10% diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, CO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healthcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%.In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (significant ST-segment depression0.1 mV and/or arrhythmia). To determine peripheral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue oxygen partial pressure (tPo2, MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventricular (LV) end-diastolic pressure, global and regional myocardial contractility (maximal change in pressure over time, LV segmental shortening, microsonometry method), LV myocardial blood flow (fluorescent microsphere technique), LV oxygen delivery, and the ratio between LV subendocardial and subepicardial myocardial perfusion. In the HSA group, critical hematocrit was found at 6.1 (1.8)% (hemoglobin, 2 g x dL(-1)), whereas all DCLHb-treated animals survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g x dL(-1)) was achieved without signs of hemodynamic instability. Although arterial oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL-1) neither oxygen delivery and oxygen uptake nor median tPo2 and hypoxic tPo2 values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals until 1.2% hematocrit was achieved. This was attributable to a higher coronary perfusion pressure (65 (22) mm Hg vs. 19 (8) mm Hg; p.05), higher subendocardial perfusion (4.1 (2.6) mL.min-1.g-1 vs. 1.2 (0.4) mL x min(-1) x g(-1)), and subendocardial oxygen delivery (5.7 (2) mL x min(-1) x g(-1), p.05) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (730); p.05) and higher regional myocardial contractility (11 (8)% vs. 6 (2)%; p.05). An increased LV end-diastolic pressure reflected LV myocardial pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted animals. In the DCLHb group, systemic vascular resistance index remained at baseline values throughout the protocol, whereas coronary vascular resistance decreased. In contrast, both variables decreased in HSA-diluted animals.DCLHb as a diluent allowed for hemodilution beyond the hematocrit value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). Even at 1.2% hematocrit (hemoglobin, 4.7 g x dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxygenation. This discrepancy in regional oxygenation might be caused by a redistribution of blood flow favoring the heart, which is related to a disproportionate decrease of coronary vascular resistance index during hemodilution with DCLHb.

Resuscitation using small volumes of hypertonic saline solutions normalizes cardiac output without fully restoring arterial pressure. This study compared the efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium load of normal saline (NS) to improve regional myocardial blood flow (MBF), contractile function, and oxygen metabolism in the presence of a critical coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were instrumented to assess left anterior descending coronary artery (LAD) flow, post-stenotic oxygen, and lactate metabolism, regional myocardial segment shortening (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD-stenosis did not affect myocardial metabolism, SS, or MBF at rest. After hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by 53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but not MAP. MBF increased above baseline values with either solution in non-stenotic while it remained at shock levels in post-stenotic myocardium, where ischemia persisted as evidenced by lactate production and depressed SS. Neither in non-stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio normalized upon resuscitation with HSDex or NS. We conclude that in the presence of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex and the identical sodium load of NS failed to restore perfusion pressure, redistributed MBF in favor of normally perfused myocardium, and did not reverse ischemia in post-stenotic myocardium.