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We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block endothelial activation. Here, we tested whether CD133MP might be shed in a CD39-dependent manner in a model of liver injury and could potentially serve as biomarkers of liver failure in the clinic.

Xenotransplantation may become clinically feasible once the mechanisms of graft loss and rejection are better understood. Inflammatory reactions to vasculature of grafted pig organs and pancreatic islets have been linked to procoagulant activation and consumption with resulting thrombosis that precludes long-term function. Although development of α-1,3-galactosyltransferase gene-knockout swine with removal of a dominant xenoantigen has been an important advance, major problems still persist.

Necrotizing fasciitis is a life threatening soft-tissue infection with a high morbidity and mortality. Prompt treatment based on extensive surgical debridement and antibiotic therapies are the therapeutic principles. The medical records of patients with necrotizing fasciitis (n = 26) from 1996 to 2005 were retrospectively analyzed. The localization of necrotizing fasciitis was most commonly the trunk (42.3%). Type I polymicrobial infection was the dominating infection. The involvement of anaerobic bacteria was associated with an increase in the number of surgical revisions (p= 0.005). Length of postoperative intensive care unit stay, duration of postoperative ventilation and mortality were significantly increased in the ASA IV-V group. Computed tomography displayed only a limited significance as diagnostic tool for initial diagnosis. In severe cases the combination of necrotic skin and soft tissue gas facilitates the correct diagnosis, which should than be followed by immediate - and most often - repeated debridement. If anaerobes are isolated an early and aggressive second look is necessary.

Objectif: Les effets de ľanémie par hémodilution ou hémodilution isovolémique (HDI) sur ľextraction ďoxygène et ľoxygénation tissulaire dans les organes périphériques après ľutilisation de transporteur ďoxygène à base ďhémoglobine comme HBOC201 ont été très étudiés, mais on connaît peu les propriétés de ľoxygénation tissulaire des solutions ďhémoglobine dans les organes centraux comme le foie. Méthode: Douze Fox-hounds ont été anesthésiés, puis assignés à un groupe témoin sans hémodilution (Groupe 1) ou soumis à la première étape de ľhémodilution isovolémique (pression artérielle pulmonaire bloquée constante) avec une solution de Ringer (Groupe 2) jusqu’à un hématocrite de 25 % et ont reçu une perfusion de seconde étape avec HBOC-201 pour obtenir une concentration ďhémoglobine de +0,6 g·dL-1. Les tensions en oxygène tissulaire (tpO2) ont été mesurées dans le muscle gastrocnémien en utilisant une sonde à injection polarographique et dans le foie au moyen ďune électrode polarographique flexible. Résultats: Tandis que le contenu en oxygène artériel et la distribution ďoxygène ont diminué avec ľhémodilution dans le Groupe 2, le ratio ďextraction globale ďoxygène hépatique et musculaire a augmenté après ľhémodilution et ľusage additionnel de HBOC-201. ľhémodilution et HBOC-201 ont fait augmenter la tpO2hépatique moyenne (mesures de base : 48 ± 9, 20 min : 53 ± 10, 60 min : 67 ± 11*, 100 min : 68 ± 7*; *P < 0,05 vs mesures de base et Groupe 1), tandis que les tensions en oxygène sont demeurées inchangées dans le Groupe 1. La tension en oxygène dans le muscle squelettique a augmenté après ľhémodilution et aussi après ľusage de HBOC-201 en comparaison des mesures de base et du groupe témoin. (P < 0,05). Conclusion: Chez le modèle animal utilisé, ľHDI avec une solution de Ringer et ľusage additionnel de HBOC-201 ont augmenté ľextraction ďoxygène et la tpO2dans le foie et le muscle squelettique, parallèlement et comparativement aux valeurs de base et au groupe témoin.

The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated.

In der Intensivmedizin stellen katheter-assoziierte thromboembolische Ereignisse eine der Hauptkomplikationen von längerfristig liegenden zentralen Venenkathetern dar. Wir berichten über eine 45-jährige Patientin, bei der im Rahmen eines langfristigen Intensivaufenthalts ein Thrombus an der Spitze eines zentralen Venenkatheters mit Hilfe der transösophagealen Echokardiographie detektiert wurde. In der Detektion von Thromben und in der Diagnostik einer Lungenembolie stehen verschiedene konkurrierende radiologische und nuklearmedizinische Verfahren sowie die transösophageale Echokardiographie zur Verfügung, deren diagnostische Wertigkeiten anhand des vorliegenden Falls kritisch abgewogen werden sollen. Wie in diesem Fallbeispiel dargestellt ist die transösophageale Echokardiographie eine verlässliche, schnell und einfach durchzuführende Methode, diese häufige Komplikation nachzuweisen und bietet die Möglichkeit eines intensivmedizinischen Monitorings des Patienten und einer Verlaufskontrolle der Therapie. In intensive care medicine, catheter-associated thromboembolism is a major complication of long-term central venous catheters. In a 45-year-old woman, a thrombus at the tip of a central venous catheter was detected by transesophageal echocardiography during her long-term stay in the intensive care unit. For the detection of thrombi and the diagnosis of pulmonary embolism, alternative methods are available: radiologic and nuclear medicine-based methods and transesophageal echocardiography. Their diagnostic value with regard to the present case is to be considered carefully. As presented in this case, transesophageal echocardiography is a reliable, quick and easy method to detect this frequent complication and allows an intensive-care monitoring and a control in therapy.

Remifentanil is used as an analgesic for different procedures performed during monitored anaesthesia care. Opioid-induced nausea and vomiting can be troublesome.

Midlatency auditory evoked responses (MLAER) can distinguish different stages of anaesthesia. We studied MLAER during emergence from propofol/sufentanil anaesthesia in relation to recovery of explicit memory.

Mid-latency somatosensory evoked responses are used to monitor the integrity of the sensory pathways intra-operatively. They can quantify the effects of anaesthetics on the central nervous system. Mid-latency auditory evoked responses have been related to cognition during anaesthesia, but there are no detailed studies using median nerve somatosensory evoked responses (MnSSER).

The history of nitrous oxide (N2O) begins with its isolation by Joseph Priestly in 1772. Some years later Humphry Davy incidentally noted its analgesic action but this fact was not recognized by surgeons. The gas was used for public entertainment and during one of these demonstrations, Horace Wells realized the therapeutic applicability of the gas. His first public demonstration at the Massachusetts General Hospital was a failure, a story that is too well-known to need re-telling.

Zusammenfassung: Das maligne neuroleptische Syndrom (MNS) stellt eine schwerwiegende Komplikation der Therapie mit antipsychotischen Pharmaka dar. Wir berichten ber einen 65-jhrigen Patienten, der zur Therapie einer schweren depressiven Episode mit psychotischen Symptomen mit Haloperidol, Diazepam und Mirtazapin eingestellt wurde. Er entwickelte viele der MNS definierenden bzw. assoziierten Zeichen und Symptome: Hyperthermie, Rigor, erhhte Kreatinphosphatkinase, Leukozytose, erhhte Leberenzyme, eingeschrnktes Bewusstsein und vegetative Strungen. Zwei Tage nach Beginn des MNS war eine sekundre Pneumonie festzustellen, die sich aufgrund einer Brustwandrigiditt entwickelt haben knnte. Die intensivmedizinische Behandlung beinhaltete das sofortige Absetzen des auslsenden Agens, die supportive Therapie mit Rehydratation und Katecholaminen sowie die Applikation von Dantrolen. Nach 23-tgiger Intensivtherapie waren alle pathologischen Werte normalisiert und der Patient wurde auf eine internistische Station berwiesen. Drei bedeutende Theorien der Pathogenese wurden aufgestellt: 1. Blockade zentraler Rezeptoren; 2. Skelettmuskelzellen als primres Zielsubstrat und 3. sympathoadrenerge Hyperaktivitt. Die Differentialdiagnose beinhaltet u. a. maligne Hyperthermie und Serotoninsyndrom.

We compared the airflow resistance of 7.5 and 8.5 mm internal diameter (i.d.) endotracheal tubes (ETTs) with that of a size 4 laryngeal mask airway (LMA). We thought that any difference in the resistance of the devices alone might be offset by the resistance of the larynx. Sixteen adult ASA physical status I and II patients (14 males, two females) undergoing general anaesthesia were anaesthetized and paralysed with intravenous propofol, ketamine and vecuronium. After insertion of the LMA, controlled ventilation (tidal volume 10 ml kg-1, frequency 12 min-1) was established with three different settings for inspiratory flow (5.5, 7.5 and 12.5 ml kg-1 s-1). Ventilation with the same settings was used after orotracheal intubation with an ETT of i.d. 7.5 mm (females) or 8.5 mm (males). The position of the LMA mask and the tip of the ETT were checked through a fibrescope. The resistance of the devices and, in case of the LMA, of the larynx, was derived by relating proximal and distal pressures (measured via catheters) to inspiratory flow. Four patients--young, tall men--had to be excluded from further study because of a leak around the LMA. In the remaining 10 males and two females, resistance of the LMA (mean (SD) at high flow, 1.19 (0.22) mbar.s litre-1 in males) was less than that of the 8.5 mm i.d. ETT (3.34 (0.52) mbar.s litre-1) (P < 0.01). However, the structures between the LMA and the trachea added another, highly variable, resistance component, so that the mean resistance of the LMA and larynx together was similar (in males: 3.20 (2.71) mbar.s litre-1) to that of the 8.5 mm ETT. In eight patients the epiglottis projected on to one-tenth to two-thirds of the distal opening of the LMA; this was in no case associated with greater resistance. Greater resistance occurred in two patients with a central LMA position and unobstructed view of the glottis and in one patient with marked lateral deviation. In conclusion, there is no clinically relevant difference between the resistance of a size 4 LMA plus that of the larynx and that of an 8.5 mm i.d. ETT.

The aim of this chapter is to discuss some of the recent findings on monitoring the depth of anaesthesia, both in general and with respect to α2-agonists. Defining the depth of anaesthesia for intra-operative monitoring is more complex than describing increasing and decreasing pharmacodynamic drug effects. Ideally, monitoring would indicate the specific components of anaesthesia—hypnosis, sedation, and analgesia—quantitatively. So far, all the parameters available reflect only parts of this whole system. Beside common clinical parameters, electrophysiological parameters (EEG and evoked potentials) have been suggested for use in evaluating the depth of anaesthesia because of their dose-related, almost unspecific signal changes. Unfortunately, defining the threshold for preventing awareness and quantifying painful events for requirement-specific treatments have not been resolved in any detail. This is fraught with even more difficulties when α2-agonists are involved because the haemodynamic response is directly attenuated and there is controversy surrounding α2-agonist-mediated EEG and evoked potential findings. The challenge of obtaining more information about the target organ—the brain—has recently been addressed by several innovative EEG analysing techniques.

Purpose:To evaluate median nerve somatosensory evoked responses during recovery from anesthesia in relation to clinical findings.

Although propofol (2,6-di-isopropylphenol) is a popular i.v. general anaesthetic, it has been suggested to have abuse potential. As many drugs of abuse act preferentially via release of dopamine in the limbic system, we investigated the action of propofol on stimulated dopamine release in the rat nucleus accumbens. Nucleus accumbens slices were superfused (1.6 ml min-1) with artificial cerebrospinal fluid at 32 degrees C. Dopamine release was evoked by electrical stimulation (10 pulses, 0.1 ms, 10 mA, 10 Hz, every 10 min) and monitored by fast cyclic voltammetry. Propofol 100 mumol litre-1 reduced stimulated dopamine release over the 2 h after administration, relative to intralipid controls, to mean 30 (SEM 2)% (P < 0.01). The dopamine D2 receptor antagonist metoclopramide 0.3 mumol litre-1 increased dopamine release but did not block the effect of propofol (38 (3)%). The selective GABAA antagonist bicuculline 24 mumol litre-1 also failed to antagonize the action of propofol (45 (3)%). The NMDA receptor antagonist dextromethorphan 10 mumol litre-1 decreased dopamine release to 57 (6)% (P < 0.01) but failed to block the inhibitory effect of propofol (46 (6)%). Although propofol has been reported to bind to D2, GABAA and NMDA receptors, failure of metoclopramide and bicuculline to block its effects suggests that an agonist action at D2 or GABAA receptors does not mediate the effects of propofol on dopamine release in the rat nucleus accumbens. The lack of effect of dextromethorphan makes an NMDA receptor antagonist action unlikely.

Ectonucleotidases influence purinergic receptor function by the hydrolysis of extracellular nucleotides. CD39 is an integral membrane protein that is a prototype member of the nucleoside 5'-triphosphate diphosphohydrolase family. The native CD39 protein has two intracytoplasmic and two transmembrane domains. There is a large extracellular domain that undergoes extensive glycosylation and can be post-translationally modified by limited proteolysis. We have identified a potential thioester linkage site for S-acylation within the N-terminal region of CD39 and demonstrate that this region undergoes palmitoylation in a constitutive manner. The covalent lipid modification of this region of the protein appears to be important both in plasma membrane association and in targeting CD39 to caveolae. These specialized plasmalemmal domains are enriched in G protein-coupled receptors and appear to integrate cellular activation events. We suggest that palmitoylation could modulate the function of CD39 in regulating cellular signal transduction pathways.

Ectonucleotidases influence purinergic receptor function by the hydrolysis of extracellular nucleotides. CD39 is an integral membrane protein that is a prototype member of the nucleoside 5′-triphosphate diphosphohydrolase family. The native CD39 protein has two intracytoplasmic and two transmembrane domains. There is a large extracellular domain that undergoes extensive glycosylation and can be post-translationally modified by limited proteolysis. We have identified a potential thioester linkage site forS-acylation within the N-terminal region of CD39 and demonstrate that this region undergoes palmitoylation in a constitutive manner. The covalent lipid modification of this region of the protein appears to be important both in plasma membrane association and in targeting CD39 to caveolae. These specialized plasmalemmal domains are enriched in G protein-coupled receptors and appear to integrate cellular activation events. We suggest that palmitoylation could modulate the function of CD39 in regulating cellular signal transduction pathways.

Background: Diaphragmatic lesions as a result of blunt or penetrating trauma are challenging to detect in the initial trauma setting. This is especially true when diaphragmatic trauma is part of a polytrauma. Complications of undetected diaphragmatic defects with incarcerating bowel are rare, but as in our patient can be serious. Case presentation: A 57-year-old female presented to the Emergency Room of our Hospital in a critical condition with 3 days of increasing abdominal pain. The initial clinical examination showed peritonism with tinkling peristaltic bowel sounds of mechanical obstruction. A thoraco-abdominal CT scan demonstrated colon prolapsed through the left diaphragmatic center with a large sero-pneumothorax under tension. As the patient was hemodynamically increasingly unstable with developing septic shock, an emergency laparotomy was performed. After retraction of the left colon, which had herniated through a defect of the tendinous center of the left diaphragm and was perforated due to transmural ischemia, large amounts of feces and gas discharged from the left thorax. A left hemicolectomy resulting in a Hartmann-type procedure was performed. A fully established pleural empyema required meticulous debridement and lavage conducted via the 7–10 cm in diameter phrenic opening followed by a diaphragmatic defect reconstruction. Due to pneumonia and recurring pleural empyema redo-debridement of the left pleural space via thoracotomy were required. The patient was discharged on day 56. A thorough history of possible trauma revealed a bicycle-fall trauma 7 months prior to this hospitalization with a surgically stabilized fracture of the left femur and conservatively treated fractures of ribs 3–9 on the left side. Conclusion: This is the first report on a primarily established empyema at the time of first surgical intervention for feco-pneumothorax secondary to delayed diagnosed diaphragmatic rupture following abdomino-thoracic blunt trauma with colic perforation into the pleural space, requiring repetitive surgical debridement in order to control local and systemic sepsis. Thorough investigation should always be undertaken in cases of blunt abdominal and thoracic trauma to exclude diaphragmatic injury in order to avoid post-traumatic complications.

Abstract. Administration of 5-HT₂ receptor agonists induced malignant hyperthermia (MH) in susceptible pigs. Furthermore, the 5-HT₂ receptor antagonist ritanserin prevented 5-HT-induced porcine MH. It has been shown that 5-HT₂ receptor agonists induce marked contractures in skeletal muscle specimens from MH susceptible (MHS) but not in specimens from normal patients. The purpose of this study was to investigate the effects of ritanserin on halothane-induced contractures in muscle specimens from MHS patients. Twenty-five patients aged 8-56 years (29.5±13.6) classified as MHS by the in vitro contracture test (IVCT) with halothane and caffeine according to the protocol of the European MH Group participated in this study. Muscle specimens were pretreated with ritanserin 10 µmol/l (n=14), 20 µmol/l (n=14) and 100 µmol/l (n=12) for 10 min and subsequently halothane was added incrementally (0.11-0.22-0.44 mmol/l) to the tissue bath as described in the European MH protocol. The results of the halothane contracture test were used as control. Following administration of halothane, muscle contractures reached a maximum of 16.9±4.2 mN. Ritanserin led to a significant inhibition of halothane-induced contractures in MHS muscles. Following pretreatment with ritanserin, halothane-induced contracture maximum was significantly smaller with 7.5±3.1 mN after 10 µmol/l ritanserin, 4.9±1.5 mN after 20 µmol/l ritanserin and 0.5±0.2 mN after 100 µmol/l ritanserin than without pretreatment. Administration of ritanserin induced at all concentrations a decrease in muscle twitch height. Increase in muscle twitch following halothane was reduced in a concentration-dependent manner by ritanserin. The presented findings indicate that 5-HT might be involved in the mechanisms of halothane-induced MH in humans. Further studies have to determine the pathophysiological role of the 5-HT system in MH, and whether ritanserin could be an alternative for treatment or prevention of halothane-induced MH.

The effects of compromised cerebral hemodynamics on intracranial blood flow velocity patterns (BFV) were studied by noninvasive transcranial Doppler sonography (TCD). Pulsatility index (PI) as an estimation of peripheral cerebral vascular resistance was additionally analyzed. TCD patterns were determined in 19 mechanically ventilated brain dead patients (group A) and 8 resuscitated or severely head injured patients (group B) with intermittent elevated intracranial pressure (ICP). Group A and B TCD data were compared to control measurements obtained in 20 healthy volunteers (group C). Normal TCD recordings (group C) were characterized by anterograde Doppler wave-forms with a predominantly high diastolic flow pattern and PI values of <1. In brain dead patients (group A), flow velocity profiles were significantly decreased. The flow curve consisted of low systolic anterograde spikes, while early diastolic flow components of low amplitudes revealed retrograde phases with a late diastolic zero flow. In some cases, total diastolic circulatory arrest was obtained. PI in brain dead patients was increased by a factor of 10 and was infinite in situations of zero net flow. The low systolic spikes and retrograde diastolic flow may be explained by the effects of reduced intracranial compliance due to increased intracranial pressure (ICP). The detection of bidirectional signals, indicating anterograde and retrograde movements of the blood column or low systolic spikes without diastolic signals, seems to be specific for the condition of brain death. Insonation of the basilar artery should be performed in order to exclude preserved perfusion of infratentorial brain regions during supratentorial circulatory arrest and vice versa. In group B patients, episodes of increased ICP predominantly affected the diastolic flow velocity component. In these patients, resistive Doppler signals with normal or reduced systolic peaks and decreased diastolic flow velocities were expressed as increases in PI. Noninvasive transcranial Doppler sonography appears to confirm cerebral circulatory arrest. Additionally, TCD may be of value for the early detection of impaired cerebral hemodynamics due to changes in intracranial compliance.

The concentration-response curves and the time course of the effects of phenylephrine (0.01-100 microM) on force of contraction and on inositol polyphosphates in isolated electrically stimulated perfused rat hearts (Langendorff technique) were studied. A nonradiometric high performance liquid chromatography metal dye detection technique was used to determine absolute concentration masses/changes of inositol polyphosphates in heart. Products measured after separation with high performance liquid chromatography were inositol 1,4,5-trisphosphate (1,4,5-IP3), inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4) and its isomer 1,3,4,6-IP4, inositol 1,3,4,5,6-pentakisphosphate (1,3,4,5,6-IP5), and inositol hexakisphosphate (IP6). 1,4,5-IP3 (significant at 10 microM) and both IP4 isomers (significant at 1 microM) increased after alpha-adrenoceptor stimulation, whereas 1,3,4,5,6-IP5 and IP6 remained unaffected. Phenylephrine had a concentration-dependent positive inotropic effect (significant at 1 microM). All effects were antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.1 microM), indicating receptor-mediated effects. In a time course study 1,4,5-IP3 was the first compound to increase significantly, within 1 min after stimulation; this rise was followed by an increase in 1,3,4,5-IP4 beginning within 2 min. The increase in all other inositol polyphosphates was slower (5-10 min). The increase in the force of contraction started at 2 min. For comparison, the effects of the beta-adrenoceptor agonist isoprenaline were studied. Isoprenaline produced a positive inotropic effect similar to that of phenylephrine, but all inositol polyphosphates remained unaffected. In conclusion, for the first time the existence of 1,3,4,5,6-IP5 and IP6 was observed in the heart. However, the physiological role of these inositol polyphosphate isomers in the heart remains to be elucidated, because, from the time course, they appear to have no acute intracellular second messenger function. Increased inositol polyphosphate turnover may be involved in the mechanism(s) whereby alpha 1-adrenoceptor stimulation produces an increase in myocardial force of contraction. Because the increase in 1,4,5-IP3 precedes and that in 1,3,4,5-IP4 coincides with the increase in the force of contraction, 1,4,5-IP3 may initiate and 1,3,4,5-IP4 may maintain the positive inotropic effect of alpha 1-adrenoceptor agonists.

Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alpha-3, G(o) alpha, Gs alpha, and G beta and myocardial levels of PTX-sensitive G proteins. Rats were treated by subcutaneous infusions, with osmotic minipumps, of 0.9% NaCl, isoprenaline (2.4 mg/kg/day), propranolol (9.9 mg/kg/day), or a combination thereof for 1, 2, 3, 4, or 8 days, and two groups were treated with NaCl or isoprenaline for 13 or 26 days. Additional groups of rats were treated with 0.24 or 0.07 mg/kg/day for 4 days to determine the dose dependency of the effects of isoprenaline. mRNA concentrations were determined by standardized slot blotting with 32P-labeled cDNA or cRNA probes. In isoprenaline-treated rats, mRNA levels of all members of the Gi alpha/G(o) alpha family increased gradually in parallel. The increase in Gi alpha-2, Gi alpha-3, and G(o) alpha mRNA levels reached significance on days 2-3, reached maximal values on days 3-4, and remained stable over the total time of treatment of up to 26 days. Compared with NaCl, maximal increases were 77% (Gi alpha-2; 16.4 versus 9.3 pg/micrograms), 58% (Gi alpha-3; 4.65 versus 2.95 pg/micrograms), and 78% (G(o) alpha; 0.40 versus 0.22 pg/microgram). Gs alpha mRNA levels (about 30 pg/micrograms) and G beta mRNA levels remained unchanged. In isoprenaline-treated rats myocardial levels of PTX-sensitive G proteins increased by maximally 54%, compared with control. The time course differed slightly from the time course of mRNA up-regulation in the first 3 days of treatment and paralleled the increase in mRNA levels from day 4 on. Propranolol had no effect on G alpha mRNA or protein levels when given alone but abolished all effects of isoprenaline when given in combination. Isoprenaline at a dose of 0.24 mg/kg/day still induced an increase in Gi alpha-2 mRNA levels of 24%, without any effects on histopathology of the myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Summary In the choice of anaesthetics and techniques the danger of a possible progressive increase of intracranial pressure (ICP) should be considered. Therefore the influence of intravenous anaesthetic agents on mean arterial pressure, ICP, and cerebral perfusion pressure (CPP) in patients with primarily increased ICP was observed under standard conditions for 20–40 minutes. Etomidate, thiopentone, propanidid, and ketamine showed remarkable effects on ICP, even in patients with disturbed cerebro-vascular reactivity. Etomidate and thiopentone cause a fall of ICP by 26%. Because of its stabilizing effects on circulation etomidate does not induce a reduction of CPP, whereas thiopentone will do so because of its depressing effect on blood pressure. Propanidid appears to be a less suitable agent when there is raised ICP, because it induces fluctuations of ICP and blood pressure up to the third minute after injection. According to our results, monoanaesthesia with ketamine cannot be recommended when there is increased ICP because it causes a prolonged increase in ICP, and reduction of blood pressure and CPP.

There are recent reports on postoperative pulmonary complications in patients with esophageal cancer who were treated preoperatively with chemotherapy and irradiation. The Hamburg Esophageal Study Group is currently undertaking a prospective randomized study to evaluate the efficacy of preoperative treatment. Postoperative pulmonary complications and mortality in these patients with either a combined preoperative treatment (group 1, n=11) or chemotherapy alone (group 2, n=9) are evaluated in the present paper. Complete remission of the tumor was found more often in group 1 (54,6%) than in group 2 (22.2%). However, postoperatively the patients of group 1 developed adult respiratory distress syndrome (ARDS; 54,6%) more frequently than in group 2 (11.1%), and all patients with ARDS died. Thus, although the combined preoperative treatment is more effective in tumor remission, it is associated with a higher respiratory failure and postoperative mortality. Therefore, the preoperative regime has now been changed by the study group. Since after the clinical manifestation of ARDS no causative clinical therapy is available up to now, attention must be focused on the prevention of respiratory failure.

Background and Objectives. Adequate postoperative pain relief has been achieved in orthopedic patients by subarachnoid bolus administration of plain bupivacaine. This prospective randomized study compares bolus injections of bupivacaine with a patient controlled infusion via subarachnoid 28-gauge microcatheters for postoperative analgesia after elective hip replacement. Methods. Forty-two patients (mean age, 69+/-11 years) were randomly allocated to one of two groups. Group 1 patients received a constant subarachnoid infusion of 0.6 mg/h of bupivacaine by a patientcontrolled device and were allowed to self-administer 0.6 mg every 30 minutes Group 2 patients received a nurse-administered bolus of 3.75 mg of plain bupivacaine on request. Pain was assessed by patients and nurses by a visual analog scale (VAS) every hour. The degree of motor block and the level of analgesia were documented every 4 hours. Hemodynamic and respiratory parameters were recorded hourly. Differences between groups were tested by analysis of variance for repeated measurement. Results. Technical problems occurred in six patients were more frequent in group 1 but none in group 2. Patient-controlled analgesia resulted in lower pain scores than bolus application during 18 postoperative hours (VAS score 19+/-19 mm in group 1 and 39+/-30 mm in group 2; P<.01). Lower total doses of bupivacaine were required in group 1 (17.6+/-4 mg) than in group 2 (22.3+/-7 mg; P<.05). The groups did not differ with respect to the degree of motor block (Bromage score 3.5+/-0.5), the sensory level (L1-2+/-1), or hemodynamic or respiratory parameters. Conclusion. In spite of a higher incidence of technical problems, patient-controlled analgesia with a continuous background infusion via microspinal catheters provides more effective postoperative analgesia, without hemodynamic or respiratory side effects, than bolus administration.

Purpose: This study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model. Methods: Following randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g · dl−1haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 μ needle probe. Results: In all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P &lt; 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P &lt; 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P &lt; 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 ± 8%, P &lt; 0.01) at the end of transfusion than in Group 1 (37 ± 13%) and 2 (32 ± 5%). In Group 3, mean tissue oxygen tension increased from 16 ± 5 mmHg after haemodilution to 56 ± 11 mmHg after transfusion (P &lt; 0.01) and was higher than in Group 1 (41 ± 9, P &lt; 0.01) and Group 2 (29 ± 11, P &lt; 0.01). While in Group 3 an augmentation of 0.7 g · dl−1haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g · dl−1and 2.1 g · dl−1were needed in Groups 1 and 2 to reach this level (P &lt; 0.01). Conclusion: The results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.

Delayed xenograft rejection is characterized by platelet activation and fibrin deposition and is thought to occur independently of complement activation. We have therefore investigated the potential for xenogeneic endothelial cells (EC) to regulate the conversion of prothrombin to thrombin, a central component of the final common pathway of coagulation and an important platelet agonist.

This study correlates the effects of propofol on cerebral blood flow (CBF) and middle cerebral artery blood flow velocity in dogs. CBF was measured using radioactive microspheres. Cerebral oxygen consumption (CMRO2) was measured with each CBF determination. Blood flow velocity was measured through a transtemporal window using a pulsed 8 MHz transcranial Doppler ultrasound system (TCD). Electroencephalogram (EEG) was continuously recorded over both cerebral hemispheres. Cardiac output (CO) was measured using an electromagnetic flow probe placed on the pulmonary artery. Baseline measures were made in all dogs (n 11) with 0.7 isoflurane end tidal and 50 N2O in O2. There were two treatment groups. In group 1 (n 6), propofol (0.8 mg/kg/min) was infused and a second measurement made at induction of EEG burst suppression (12 ± 2 min). CBF and CMRO2decreased by 70 and mean blood flow velocity decreased by 60. Blood pressure, heart rate, and CO did not change. Propofol infusion was discontinued and all parameters were measured following recovery of EEG to baseline activity (48 ± 9 min). CBF and blood flow velocity increased 35 and 25, respectively, and CMRO2increased by 32 during this period. A second propofol infusion (0.8 mg/kg/min) was started and all cerebral and systemic hemodynamic parameters were again determined at induction of EEG burst suppression (12 ± 2 min). CBF decreased 35 and blood flow velocity decreased 25 to levels seen during the first propofol infusion. Over the entire study, changes in CBF correlated with changes in blood flow velocity (r 0.86, p < 0.05). In group 2 (n 5), four control measures were made at the same time intervals as in group 1. Baseline CBF and blood flow velocity were lower in group 2 compared to group 1 but these measures did not change over time. Our results show that propofol produces marked decreases in CBF in dogs and that these changes are closely correlated with CBF velocity.

Abstract.: The rapid sequence induction of anaesthesia in patients with an increased risk of pulmonary aspiration is a quite involved procedure associated with many potential dangers. A new nasogastric balloon tube has been developed, which will prevent the reflux of gastric contents by blocking the cardia with a balloon. It was the aim of this initial study to assess the efficiency of the tube in animals, healthy volunteers and patients. Methods. With the approval of the Animal Ethics Committee, a total of 16 anaesthetised pigs were used for the animal experiments. Balloon occlusion of the cardia was performed in 10 pigs. Six further pigs with an unblocked cardia served as controls. Vomiting and regurgitation was provoked in each animal using six different manoeuvres while the gastro-oesophageal (lower oesophageal) sphincter and intragastric pressures were monitored and the lower oesophagus was continuously inspected using an endoscope. With local Ethics Committee approval and informed written consent, (1) repeated vomiting was provoked in 16 awake, healthy adult volunteers (10 females, 6 males, 29�4 years) with a fluid-filled stomach in the presence and in the absence of balloon occlusion of the cardia, while intragastric pressure was monitored, and (2) 30 patients (21 – 89 years) with an increased risk of pulmonary aspiration scheduled for abdominal or traumatologic surgery received conventional induction of anesthesia after blocking of the cardia with the balloon. Results. Pigs (n=10) with a blocked cardia showed no gastrooesophageal reflux during a total of 60 manipulations to provoke vomiting and regurgitation, while 28 of the 36 provoking manipulations induced reflux in pigs (n=6) with an unblocked cardia. Among the healthy volunteers with a blocked cardia (n=16), reflux of gastric contents was not observed during repeated attempts to stimulate vomiting. After termination of the occlusion of the cardia, reflux was able to be induced by 14 of the 16 volunteers. In 30 patients with an increased risk of pulmonary aspiration the cardia was blocked and anaesthesia was induced using a mask and manual ventilation without encountering any problems. The average time from loss of consciousness to tracheal intubation was 164�8 s. Conclusions. It is concluded from the present results, with further clinical studies pending, that the gastric balloon probe permits low-risk conventional induction sequence of anaesthesia in patients with an increased risk for pulmonary aspiration and that the device may also be safely used during the extubation phase.

Desflurane has been reported to cause tachycardia and hypertension during induction of anaesthesia. The aim of this study was to determine the effects of desflurane on cerebral blood flow (CBF) velocity using transcranial Doppler ultrasonography in a setting that closely resembled usual clinical practice. In two groups (n = 9 in each) ASA Grade I or II patients, anaesthesia was induced with etomidate and vecuronium intravenously (i.v.), sufentanil (0.3 μg kg⁻¹ i.v.) was added in the second group. Patients were ventilated by facemask for 2 min before desflurane was administered in steps of 0.5 MAC min⁻¹ until 1.5 MAC was reached and maintained for 7 min. Haemodynamic variables and CBF velocity in the middle cerebral artery (MCA) were monitored throughout the study period. In group 1 heart rate increased to 108 ± 2 b.p.m. (37% increase) whereas MAP increased to 114 ± 6 mmHg after administration of desflurane (33% increase). CBF velocity increased to 86 ± 7 cm s⁻¹ (69% increase). In group 2 no significant changes in systemic haemodynamic responses were measured after desflurane administration; however, CBF velocity increased to 73 ± 5 cm s⁻¹ (59% increase). The results indicate that desflurane increases CBF velocity concurrently with induction of tachycardia and hypertension. Although sufentanil and N2O attenuate the systemic haemodynamic alterations caused by desflurane, the CBF velocity increases. These data suggest that the abrupt addition of desflurane may have adverse consequences in patients at risk for intracranial hypertension.

A genetic disorder of the calcium releasing ryanodine receptor has recently been postulated in malignant hyperthermia (MH) and ryanodine-induced contractures differ between subjects who are malignant hyperthermia susceptible (MHS) and non-susceptible (MHN). We tested 39 patients from 26 families for MH, using the procedure of the European Malignant Hyperthermia Group. A ryanodine contracture test was performed by both cumulative (0.4–10.0 μmol litre−1every 3min) and bolus (10.0 μmol litre−1) application. Contracture with cumulative ryanodine application started significantly earlier in MHS (9.6 (SEM 0.5) min) than in MHN patients (24.6 (1.3) min). A significant difference in start of contracture between MHS (4.8 (0.6) min) and MHN (14.5 (0.6) min) patients occurred also after bolus application of ryanodmne. The ryanodine contracture test seems to be a potentially specific in vitrodiagnostic test for MH.

Desflurane has been reported to cause tachycardia and hypertension during induction of anaesthesia. The aim of this study was to determine the effects of desflurane on cerebral blood flow (CBF) velocity using transcranial Doppler ultrasonography in a setting that closely resembled usual clinical practice. In two groups (n= 9 in each) ASA Grade I or II patients, anaesthesia was induced with etomidate and vecuronium intravenously (i.v.), sufentanil (0.3 μg kg−1i.v.) was added in the second group. Patients were ventilated by facemask for 2 min before desflurane was administered in steps of 0.5 MAC min−1until 1.5 MAC was reached and maintained for 7 min. Haemodynamic variables and CBF velocity in the middle cerebral artery (MCA) were monitored throughout the study period. In group 1 heart rate increased to 108 ± 2 b.p.m. (37% increase) whereas MAP increased to 114 ± 6 mmHg after administration of desflurane (33% increase). CBF velocity increased to 86 ± 7 cm s−1(69% increase). In group 2 no significant changes in systemic haemodynamic responses were measured after desflurane administration; however, CBF velocity increased to 73 ± 5 cm s−1(59% increase). The results indicate that desflurane increases CBF velocity concurrently with induction of tachycardia and hypertension. Although sufentanil and N2O attenuate the systemic haemodynamic alterations caused by desflurane, the CBF velocity increases. These data suggest that the abrupt addition of desflurane may have adverse consequences in patients at risk for intracranial hypertension.

A 21-year-old man suffered from exertional heat stroke with impaired consciousness and rhabdomyolysis after strenuous physical exercise. Within two weeks the patient recovered completely without any specific therapy. Based on the symptoms and laboratory investigations, this episode suggested a moderate form of malignant hyperthermia. An in vitro contracture test was performed and a predisposition to malignant hyperthermia was diagnosed; other muscular diseases were excluded by histological examination. At present, the in vitro contracture test is the only method used to determine susceptibility to malignant hyperthermia and should be performed when the diagnosis is suggested on clinical grounds.

In end-stage heart failure due to idiopathic dilated cardiomyopathy ß1-adrenoceptors are downregulated and G1a-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on ß-adrenoceptor density and Gia-proteins in sequential endomyocardial biopsies. Nineteen patients with mild to moderate congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II–III) were studied before and after 8–11 weeks of therapy. Patients were randomised into a captopril and a control group; 9 patients received captopril 12.5–50 mg per day, (divided in 2–3 doses) p.o. in addition to “conventional” therapy with digoxin and diuretics, and 10 controls received “conventional” therapy only. Echocardiography, spiroergometry, right heart catheterisation and endomyocardial biopsies were performed before (baseline) and after treatment. Compared to baseline, captopril increased total ß-adrenoceptor density by selectively increasing ß1-adrenoceptors (31.6 vs 41.2 fmol·mg-1; p<0.05) but had no significant effect on Gia-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial ß1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.

Summary Haemodynamic studies were carried out in 12 patients who had sustained severe head injury. Radial artery pressure (AP), pulmonary artery pressure (PAP), central venous pressure (CVP), and pulmonary wedge pressure (PAWP) were directly measured. Heart rate was monitored from the ECG, and cardiac output (CO) was measured intermittently by the thermodilution technique. Arterial and mixed venous blood samples were withdrawn simultaneously for measurement of PH, PCO2, PO2, and oxygen saturation. Additional cardiovascular data were calculated from standard formulae. The haemodynamic pattern in these head-injured patients was characterized by high cardiac index, low systemic vascular resistance, moderately high systemic pressure and heart rate, high pulmonary artery pressure and wedge pressure, and normal stroke index. These findings may be the result of autonomic or adrenergic stimulation by the injured brain.

Zusammenfassung An 131 Schädel-Hirn-Traumatisierten wurde festgestellt, wie die Schwere des Schädel-Hirn-Traumas den Krankheitsverlauf beeinflußt, wann und in welchem Umfang röntgenologisch und blutgasanalytisch bestimmbare Lungenveränderungen auftraten, wodurch sie verursacht wurden bzw. ob dem Sauerstoff in hoher Konzentration ein verlaufsbestimmender Einfluß zugeordnet werden konnte.

Platelet activation and microthrombus formation are invariable features of xenograft rejection and the vascular injury observed when porcine organs are transplanted into primates. This pathological process could be mediated, at least in part, by aberrant interactions of von Willebrand Factor (vWF) associated with the donor vasculature with host platelets. Unlike human vWF, native porcine vWF (pvWF) interacts with human GPIb independently of shear stress or nonphysiological stimuli, eg, ristocetin. We therefore contrasted the potential of isolated human and porcine vWF–A1-domains to interact with human platelets in vitro. Both human and porcine vWF–A1-domains expressed as glycosyl phosphatidylinositol–linked FLAG fusion proteins on COS-7 cells induced GPIb-dependent aggregation and intracellular Ca++ uptake of platelets, independent of both the remainder of the vWF protein and additional modifying factors. Porcine A1-domains were more potent than human homologues, and in addition ristocetin could boost platelet aggregation only with the human A1-domain. Putative conformational changes in the porcine A1-domain could result in the heightened, ristocetin-independent interactions observed with human platelets and may be of importance for xenograft survival.

The relation between left ventricular end-systolic wall stress (ESWS) and the velocity of circumferential fibre shortening (Vcfs) was examined in four non-random groups with 12 patients each. In group A, preload was increased by the administration of hydroxyethylstarch 30 mL min−1. In group B, preload was reduced by administering nitroglycerine 4.0±0.8 mg h−1. A change in pulmonary capillary wedge pressure by 3 mmHg was taken to be the end point for preload manipulation. To assess a change in the relation between ESWS and Vcfs, patients in group C received adrenaline at an infusion rate of 4 g min−1. Patients in group D served as the controls. Geometric variables of ESWS and Vcfs were determined by transoesophageal echocardiography. A linear model was used to assess the relation between ESWS and Vcfs within each group by regression analysis, and analysis of covariance performed to detect significance of intragroup and intergroup differences (P<0.005). No significant changes were found during preload intervention. With adrenaline, Vcfs increased significantly for a given ESWS. It is concluded that the relation between ESWS and Vcfs, in a multiple patient setting, is independent of modest preload changes and may have the potential to indicate inotropic effects.

Three months before this study, susceptibility for malignant hyperthermia (MH) had been tested in 15 pigs. In all pigs, MH was triggered by administration of 1% halothane. Brain electrical activity was examined during therapy of MH with and without administration of dantrolene. From the EEG, power densities in selected frequencies and the median frequency of the power spectrum were calculated. Therapy was started when severe respiratory changes were observed (PaCO2 > 10 kPa, mixed venous oxygen tension (PvO2) < 4 kPa). At this time, heart rate exceeded 150 beat min-1, mean arterial pressure (MAP) was less than 60 mm Hg and median frequency was less than 2 Hz. EEG was isoelectric (n = 6) or showed slow polymorphic delta-activity. For therapy, administration of all anaesthetics was terminated, 100% oxygen was delivered and ventilation was increased four-fold. Acidosis was treated by administration of sodium bicarbonate 2-4 mmol litre-1 kg-1. Animals were allocated randomly to one of two groups: group I (control, n = 7) received no dantrolene; group II (n = 8) received dantrolene 2.5 mg kg-1 i.v. All variables were measured over a period of 60 min after therapy: EEG, HR and MAP were recorded continuously and blood-gas tensions, arterial potassium and glucose concentrations and pH were measured every 150 s. In group I (no dantrolene) minor, transient improvements in EEG activity were noted, but all animals died within 15-25 min after the start of therapy. In dantrolene-treated animals, EEG total power and median frequency increased within 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

A genetic disorder of the calcium releasing ryanodine receptor has recently been postulated in malignant hyperthermia (MH) and ryanodine-induced contractures differ between subjects who are malignant hyperthermia susceptible (MHS) and non-susceptible (MHN). We tested 39 patients from 26 families for MH, using the procedure of the European Malignant Hyperthermia Group. A ryanodine contracture test was performed by both cumulative (0.4-10.0 mumol litre-1 every 3 min) and bolus (10.0 mumol litre-1) application. Contracture with cumulative ryanodine application started significantly earlier in MHS (9.6 (SEM 0.5) min) than in MHN patients (24.6 (1.3) min). A significant difference in start of contracture between MHS (4.8 (0.6) min) and MHN (14.5 (0.6) min) patients occurred also after bolus application of ryanodine. The ryanodine contracture test seems to be a potentially specific in vitro diagnostic test for MH.

We have compared patients' and nurses' assessments of postoperative pain and anxiety after different analgesic treatments. Sixty orthopaedic patients were allocated randomly to receive i.v. piritramide (either nurse-controlled or patient-controlled) or subarachnoid bupivacaine (nurse-controlled or patient-controlled). Patients and nurses assessed pain and anxiety using a visual analogue scale (AS; 1-100 mm). Pain and anxiety ratings of patients and nurses were significantly correlated (Spearman's r 0.69; P&lt;0.001). In general patients' pain scores were higher than nurses' scores (patients' median VAS=34 (range 1-76) mm; nurses VAS 21 (1-59) mm) and for all groups except the patient-controlled subarachnoid bupivacaine groups, where they were significantly higher (P&lt;0.01). Discrepancy in pain estimates between patients and nurses increased with the level of pain. The relationship between patients' and nurses' anxiety scores was less clearly defined and did not depend on the level of anxiety.
Key words: analgesia, patient-controlled; analgesia, nurse-controlled; pain, postoperative; complications, anxiety

The relation between left ventricular end-systolic wall stress (ESWS) and the velocity of circumferential fibre shortening (Vcfs) was examined in four non-random groups with 12 patients each. In group A, preload was increased by the administration of hydro- xyethylstarch 30 mL min⁻¹. In group B, preload was reduced by administering nitroglycerine 4.0±0.8 mg h⁻¹. A change in pulmonary capillary wedge pressure by 3 mmHg was taken to be the end point for preload manipulation. To assess a change in the relation between ESWS and Vcfs, patients in group C received adrenaline at an infusion rate of 4 g min⁻¹. Patients in group D served as the controls. Geometric variables of ESWS and Vcfs were determined by transoesophageal echocardiography. A linear model was used to assess the relation between ESWS and Vcfs within each group by regression analysis, and analysis of covariance performed to detect significance of intragroup and intergroup differences (P&lt;0.005). No significant changes were found during preload intervention. With adrenaline, Vcfs increased significantly for a given ESWS. It is concluded that the relation between ESWS and Vcfs, in a multiple patient setting, is independent of modest preload changes and may have the potential to indicate inotropic effects.

Xenograft rejection may predispose to vascular thrombosis because of putative cross-species' functional incompatibilities between natural anticoagulants present on the donor endothelium and host activated coagulation factors. For example, porcine thrombomodulin expressed on porcine aortic endothelial cells (PAEC) does not provide the expected thrombomodulin(TM)-cofactor activity for human protein C in the presence of human thrombin. In addition, TM may be down-regulated after cellular activation. Our aim was to express human TM cofactor activity in PAEC and to study the proinflammatory effect of tumor necrosis factor-α (TNF-α) on stable expressed human thrombomodulin in vitro.

Chronic ß-adrenoceptor stimulation leads to desensitization of the myocardial adenylyl cyclase signalling pathway which includes ß-adrenoceptor downregulation and upregulation of Gi-protein a-subunits. However, these investigations have mainly been done in cellular preparations. In this study we report that isoprenaline infusion in vivo leads to an increase in myocardial Gia and present evidence for functional consequences of this increase.