RESUMEN
BACKGROUND: The introduction of the diagnosis-related groups reimbursement system has increased cost pressures. Due to the interaction of many different professional groups, analysis and optimization of internal coordination and scheduling in the operating room (OR) is mandatory. The aim of this study was to analyze the processes at a university hospital in order to optimize strategies by identifying potential weak points. METHODS: Over a period 6 weeks before and 4 weeks after intervention processes time intervals in the OR of a tertiary care hospital (university hospital) were documented in a structured data collection sheet. RESULTS: The main reason for lack of efficiency of labor was underused OR utilization. Multifactorial reasons, particularly in the management of perioperative interfaces, led to vacant ORs. A significant deficit was in the use of OR capacity at the end of the daily OR schedule. After harmonization of working hours of different staff groups and implementation of several other changes an increase in efficiency could be verified. CONCLUSIONS: These results indicate that optimization of perioperative processes considerably contribute to the success of OR organization. Additionally, the implementation of standard operating procedures and a generally accepted OR statute are mandatory. In this way an efficient OR management can contribute to the economic success of a hospital.
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Hospitales Universitarios/organización & administración , Quirófanos/organización & administración , Flujo de Trabajo , Citas y Horarios , Grupos Diagnósticos Relacionados , Eficiencia Organizacional , Alemania , Hospitales Universitarios/economía , Quirófanos/economía , Atención Perioperativa , Admisión y Programación de PersonalRESUMEN
The implementation of diagnosis-related groups (DRGs) sharply increased economic pressure on hospitals. Hence, process optimization was focussed on cost-intensive areas, namely the operation room (OR) departments. Work-flow in the OR is characterized by a mandatory interlocking of the job functions of many different occupational groups and the availability of a variety of different materials. Alternatives for staff assignment optimization have been published in numerous publications dealing with the importance of OR management. In this connection the issue of material logistics in the context of OR management has not been frequently addressed. In order to perform a surgical procedure according to plan, one depends on personnel and on timely availability of the materials needed. Supply of sterilized materials is of utmost importance, because in most hospitals sterilized surgical devices constitute a critical resource. In order to coordinate the OR process with the production flow of sterilized materials, an organizational connection to the OR management makes sense. Hence, in a German university hospital the Department of Hospital Sterile Supplies was integrated into the OR management of the Department of Anesthesiology. This led to a close coordination of work-flow processes, and concomitantly a significant reduction of production costs of sterile supplies could be achieved by direct interaction with the OR. Thus, hospital sterile supplies can reasonably be integrated into an OR management representing a new interesting business area for OR organization.
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Materiales Biomédicos y Dentales/provisión & distribución , Quirófanos/economía , Quirófanos/organización & administración , Esterilización , Servicio de Anestesia en Hospital/organización & administración , Alemania , Humanos , Auxiliares de Cirugía , Organización y Administración , Admisión y Programación de Personal , Procedimientos Quirúrgicos Operativos , Recursos HumanosRESUMEN
BACKGROUND AND OBJECTIVE: Tissue depletion of adenosine during endotoxaemia has previously been described in the lung. Therapeutic approaches to prevent adenosine depletion and the role of A1 and A2 receptor agonists, however, have not been investigated until now. METHODS: In isolated and ventilated rabbit lungs, it was tested whether pretreatment with adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 10(-7) mol, n = 6) or A2 receptor agonist 5'-(N-cyclopropyl)-carboxyamido adenosine (CPCA; 10(-7) mol, n = 6) prior to injection of lipopolysaccharide (LPS) (500 pg mL-1) influenced pulmonary artery pressure (PAP), pulmonary energy content and oedema formation as compared with controls, solely infused with LPS (n = 6). Release rates of adenosine and uric acid were determined by high-performance liquid chromatography. Pulmonary tissue concentrations of high-energy phosphates were measured and the adenine nucleotide pool, adenosine 5'-triphosphate (ATP)/adenosine 5'-diphosphate (ADP) ratio and adenylate energy charge of the pulmonary tissue were calculated. RESULTS: Administration of LPS induced increases in PAP within 2 h up to 20.8 +/- 2.9 mmHg (P < 0.01). While pretreatment with the A1 agonist merely decelerated pressure increase (13.8 +/- 1.1 mmHg, P < 0.05), the A2 agonist completely suppressed the pulmonary pressure reaction (9.6 +/- 1.0 mmHg, P < 0.01). Emergence of lung oedema after exclusive injection of LPS up to 12.0 +/- 2.9 g was absent after A1 (0.6 +/- 0.5 g) and A2 (-0.3 +/- 0.2 g) agonists. These observations were paralleled by increased adenosine release rates compared with LPS controls (P < 0.05). Moreover, tissue concentrations of ADP, ATP, guanosine 5'-diphosphate, guanosine 5'-triphosphate, nicotinamide-adenine-dinucleotide and creatine phosphate were significantly reduced after LPS. Consequently, the calculated tissue adenine nucleotide pool and the adenylate energy charge increased after adenosine receptor stimulation (P = 0.001). CONCLUSIONS: Adenosine A1- and A2-receptor agonists reduced LPS-induced vasoconstriction and oedema formation by maintenance of tissue energy content. Thus, adenosine receptor stimulation, in particular of the A2 receptor, might be beneficial during acute lung injury.
Asunto(s)
Adenosina/análogos & derivados , Endotoxinas/farmacología , Metabolismo Energético/efectos de los fármacos , Pulmón/efectos de los fármacos , Edema Pulmonar/prevención & control , Receptores Purinérgicos P1/efectos de los fármacos , Adenosina/metabolismo , Adenosina/farmacología , Agonistas del Receptor de Adenosina A1 , Agonistas del Receptor de Adenosina A2 , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Análisis de Varianza , Animales , Presión Sanguínea/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Modelos Animales de Enfermedad , Endotoxemia/metabolismo , Endotoxemia/prevención & control , Femenino , Lipopolisacáridos/administración & dosificación , Pulmón/metabolismo , Arteria Pulmonar/efectos de los fármacos , Conejos , Síndrome de Dificultad Respiratoria/metabolismo , Factores de Tiempo , Ácido Úrico/metabolismo , Vasoconstricción/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: An anti-inflammatory effect of alpha2-adrenoreceptor agonists has been suggested. Phospholipase A2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A2 activity in an established in vitro model. METHODS: Human being platelet membranes containing active phospholipase A2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A2 was measured by a radioisotope technique. RESULTS: A massive increase in phospholipase A2 activity was measured after clonidine exposure leading to final values of 92.5 +/- 3.1 pmol mg protein(-1) min(-1) (4.5-fold higher than control values; P < or = 0.01 vs. control). After clonidine exposure the maximal reaction velocity increased, while the Michaelis-Menten constant did not change. The Lineweaver-Burk representation suggested an interaction of clonidine with the phospholipase A2-substrate complex as well as the phospholipase A2 molecule. CONCLUSION: We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A2.
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Agonistas alfa-Adrenérgicos/farmacología , Antiinflamatorios/farmacología , Plaquetas/enzimología , Membrana Celular/enzimología , Clonidina/farmacología , Fosfolipasas A/metabolismo , Adyuvantes Anestésicos/farmacología , Plaquetas/ultraestructura , Femenino , Fosfolipasas A2 Grupo IV , Humanos , Técnicas In Vitro , Masculino , Fosfolipasas A2RESUMEN
BACKGROUND AND OBJECTIVE: ProSeal Laryngeal Mask Airway (PLMA) and Laryngeal Tube Suction (LTS), supraglottic airway devices allowing gastric drainage, were compared in this prospective, randomized study for airway management under conditions with elevated intra-abdominal pressure induced by capnoperitoneum. METHODS: Fifty patients undergoing elective gynaecological laparoscopic surgery were randomized to two groups of 25 each. After induction of general anaesthesia, devices were inserted, correct placement was verified, airway leak pressure was measured, and a gastric tube was inserted. Ease of insertion, quality of airway seal, risk of gastric insufflation and patient comfort were investigated. RESULTS: There were no differences in patient characteristics data for both groups. First-time insertion success rates were comparable for both groups: 92%--first attempt, 8%--second attempt for PLMA and LTS. Time until delivery of the first tidal volume for PLMA and LTS was 23.2 +/- 6.1 and 23.5 +/- 6.6s, airway leak pressure was 45.4 +/- 4.9 cmH2O and 45.6 +/- 6.7 cmH2O with cuff pressures adjusted to 60 cmH2O. No gastric insufflation, gas loss or signs of regurgitation were detected. Placement of a gastric tube was successful in all patients. Patients were questioned for sore throat and dysphagia after removal of devices. Sore throat was stated in 1%/0% (PLMA) and 8%/4% (LTS) after 6/24 h, dysphagia in 4%/4% (PLMA) and 12%/4% (LTS). CONCLUSIONS: Both devices provide a secure airway even under conditions of elevated intra-abdominal pressure. In this pilot study, no differences concerning handling or quality of airway seal were detected between PLMA and LTS.
Asunto(s)
Gastroscopía , Intubación Intratraqueal , Laparoscopía , Máscaras Laríngeas , Respiración Artificial/métodos , Adulto , Anestesia General , Femenino , Humanos , Insuflación , Complicaciones Intraoperatorias/epidemiología , Intubación Gastrointestinal , Persona de Mediana Edad , Monitoreo Intraoperatorio , Faringitis/epidemiología , Neumoperitoneo Artificial , Estudios Prospectivos , SucciónRESUMEN
CASE REPORT: In our case, a 48-year-old healthy woman undergoing elective tympanoplasty under general anesthesia received an infusion of 2 g dipyrone in 100 ml 0.9% sodium chloride solution for pain prophylaxis. After receiving 1 g dipyrone within 5 min, the patient exhibited a cardiocirculatory failure and cyanosis and had to be resuscitated. After 20 min of cardiopulmonary resuscitation and administration of 3mg epinephrine and 2 mg norepinephrine, a stable circulation was reestablished. After exclusion of a fulminant pulmonary embolism and a primary cardiac event by computer tomography, electrocardiogram and enzyme diagnostics, the patient was transferred to an intensive care unit where she was mechanically ventilated for a period of 6 h. After 2 days of intensive monitoring, she was transferred to a peripheral ward,where she exhibited a normal neurological status and stable cardiocirculatory condition. A postoperatively performed allergy testing revealed a type I sensitization to dipyrone, which was responsible for the intraoperative cardiocirculatory failure due to a massive anaphylactic reaction. However, in this case, the typical symptoms of allergic reactions such as erythema, edema or bronchospasm were missing, which did not allow for an immediate diagnosis. CONCLUSION. Regarding the frequent perioperative use of dipyrone and the severity of anaphylaxis observed in this case, it should be considered that this analgesic should be applied intravenously only if adequate safety measures such as emergency therapy option and patient monitoring are guaranteed as recommended by the German drug regulation authority since 1982.
Asunto(s)
Anafilaxia/fisiopatología , Antiinflamatorios no Esteroideos/efectos adversos , Dipirona/efectos adversos , Choque/fisiopatología , Cianosis/inducido químicamente , Epinefrina/uso terapéutico , Femenino , Liberación de Histamina , Humanos , Persona de Mediana Edad , Norepinefrina/uso terapéutico , Respiración Artificial , Choque/etiología , Pruebas Cutáneas , Timpanoplastia , Vasoconstrictores/uso terapéuticoRESUMEN
Endothelin-1 is the most potent vasoconstrictor known to date. This peptide is believed to play a pathophysiological role in the development of vasospasm, the most important complication of subarachnoid hemorrhage (SAH). In the present study we investigated the release of endothelin-1 in SAH and analyzed the cellular source of this peptide. At a protein and mRNA level we were able to show that endothelin-1 is produced by mononuclear leukocytes. Complementary in vitro studies revealed that aging and subsequent hemolysis of blood is sufficient to induce production of endothelin-1 by mononuclear leukocytes. Thus, cerebrospinal fluid-derived mononuclear leukocytes are a source of endothelin-1 in patients suffering from SAH. This finding may have important therapeutic implications as anti-leukocyte strategies could prevent cerebrovascular complications in SAH patients.
Asunto(s)
Endotelina-1/sangre , Endotelina-1/metabolismo , Hemorragia Subaracnoidea/metabolismo , Adulto , Anciano , Aneurisma/sangre , Aneurisma/líquido cefalorraquídeo , Aneurisma/diagnóstico , Velocidad del Flujo Sanguíneo , Isquemia Encefálica/sangre , Isquemia Encefálica/líquido cefalorraquídeo , Isquemia Encefálica/diagnóstico , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Heme oxygenase (HO) plays a pivotal role for the maintenance of liver blood flow and hepatocellular integrity after hemorrhagic shock. We investigated the role of Kupffer cells and neutrophils as paracrine modulators of hepatocellular HO-1 gene expression in a rat model of hemorrhage and resuscitation. Male Sprague-Dawley rats (n = 6-10/group) were anesthetized (pentobarbital, 50 mg/kg intraperitonal) and subjected to hemorrhagic shock (mean arterial blood pressure: 35 mmHg for 60 min) or a sham protocol. Based on the time course of HO-1 gene expression, the effect of various antioxidants, Kupffer cell blockade [gadolinium chloride (GdCl3); 10 mg/kg; 24 h prior to hemorrhage or dichloromethylene diphosphonate (Cl2MDP); 1 mg/kg; 2 days prior to hemorrhage], or neutrophil depletion (vinblastine, 0.5 mg/kg, 5 days prior to hemorrhage) on induction of the HO-1 gene was assessed at 5 h of resuscitation, i.e., the time point of maximal induction. Kupffer cell blockade and antioxidants abolished HO-1 mRNA and protein induction after hemorrhage, while neutrophil depletion failed to affect hepatocellular HO-1 gene expression. In addition, Kupffer cell blockade aggravated hepatocellular injury. N-formyl-methionine-leucyl-phenylalanin (fMLP) induced a substantial influx of neutrophils into the liver but failed to induce hepatocellular HO-1 mRNA expression. These data suggest that Kupffer cells but not neutrophils induce an adaptive hepatocellular stress response after hemorrhage and resuscitation. Oxygen-free radicals released by Kupffer cells may serve as paracrine regulators of a hepatocellular stress gene which is necessary to maintain liver blood flow and integrity under stress conditions.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Hemo Oxigenasa (Desciclizante)/genética , Hepatocitos/enzimología , Macrófagos del Hígado/fisiología , Neutrófilos/fisiología , Choque Hemorrágico/genética , Choque Hemorrágico/fisiopatología , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Presión Sanguínea , Células Cultivadas , Cromanos/farmacología , Ácido Clodrónico/farmacología , Deferoxamina/farmacología , Modelos Animales de Enfermedad , Gadolinio/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1 , Macrófagos del Hígado/efectos de los fármacos , Masculino , Neutrófilos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Resucitación , Choque Hemorrágico/enzimología , Factores de Tiempo , Vinblastina/farmacologíaRESUMEN
Subarachnoidal release of inflammatory cytokines (interleukin (IL)-1beta, IL-6, and tumour necrosis factor (TNF)-alpha) was characterised in 35 patients with subarachnoid haemorrhage (SAH) and control subjects and compared with development of complicating haemodynamic abnormalities in basal cerebral arteries and clinical outcome. Serial analysis allowed the observation of a subacute response profile of these key mediators of inflammation in the subarachnoidal space. This compartmentalised inflammatory host response was closely associated in time and extent with development of increased blood flow velocities in the basal cerebral vessels as recorded by transcranial Doppler sonography. Moreover, intrathecal secretion of inflammatory cytokines was significantly increased in patients with poor clinical outcome. Together, these findings suggest a role of excessive compartmentalised inflammatory host response in pathogenesis of cerebrovascular complications after SAH.
Asunto(s)
Arterias Cerebrales/fisiopatología , Circulación Cerebrovascular/fisiología , Citocinas/sangre , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/fisiopatología , Vasoespasmo Intracraneal/sangre , Vasoespasmo Intracraneal/fisiopatología , Adulto , Anciano , Citocinas/líquido cefalorraquídeo , Citocinas/fisiología , Femenino , Humanos , Inflamación/sangre , Inflamación/fisiopatología , Interleucina-1/sangre , Interleucina-1/líquido cefalorraquídeo , Interleucina-1/fisiología , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Interleucina-6/fisiología , Masculino , Persona de Mediana Edad , Pronóstico , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Learning curves for anesthesia procedures in adult patients have been determined, but no data are available on procedures in pediatric anesthesia. The aim of this study was to assess the number of caudal blocks needed to guarantee a high success rate in performing caudal epidural analgesia in children. METHODS: At a teaching hospital, the technical skills of 7 residents in anesthesiology who performed caudal blocks were evaluated during 4 months using a standardized self-evaluation questionnaire. At the start of the study period, the residents had no prior experience in pediatric anesthesia or in performing caudal epidural blocks. All residents entered the pediatric rotation after a minimum of 1 year of training in adult general and regional anesthesia. The blocks were rated using a binary score. For comparison, the success rates of 8 experienced staff anesthesiologists were collected during the same period using the same self-evaluation questionnaire. Statistical analyses were performed by generating individual and institutional learning curves using the pooled data. The learning curves were calculated with the aid of a least-square fit model and 95% confidence intervals were estimated by a Monte Carlo procedure with a bootstrap technique. RESULTS: The success rate of residents was 80% after 32 procedures (95% confidence interval of 0.59 to 1.00). The pooled success rate of the staff anesthesiologists was 0.73 (mean) with a standard deviation of 0.45, which was not statistically different from the success rate of the residents. CONCLUSION: High success rates in performing caudal anesthesia in pediatric patients can be acquired after a limited number of cases. Success rates of residents learning this procedure are comparable to the results of staff anesthesiologists.
Asunto(s)
Anestesia Caudal , Anestesia Epidural , Anestesiología/educación , Niño , Hospitales de Enseñanza , Humanos , Programas de Autoevaluación , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Elevated endothelin-1 (ET-1) levels have been detected during sepsis. The aim of the study was to examine the role of thromboxane A2 (TXA2) and ET-1 in pulmonary vascular reactions after endotoxin (LPS) challenge. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Twenty-four adult rabbits of either sex. INTERVENTIONS: Experiments were performed on 30 isolated and ventilated rabbit lungs, which were perfused with a saline solution containing 10% autologous blood. MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial pressure and lung weight gain were continuously registered. Perfusate samples were drawn intermittently to determine ET-1, TXA2, and prostacyclin (PGI2) concentrations. LPS isolated from Escherichia coli (0.5 mg/mL; n = 6) was added to the perfusate. A marked pulmonary arterial pressure increase followed by massive edema formation after 60 mins was observed after LPS injection. At the same time, elevated TXA2 and PGI2 levels in the perfusate were measured. ET-1 was detected 30 mins after LPS infusion (13.4+/-2.6 fmol/L). Pretreatment with the ET(A) receptor antagonist LU135252 (10(-6) M; n = 6) almost completely suppressed the pressure reaction after endotoxin injection (p < .01 at 50 and 60 mins) and reduced edema formation (p < .05). The cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6) was as effective as LU135252 in preventing vascular reactions after LPS injection. CONCLUSIONS: Pretreatment with the ET(A) receptor antagonist LU135252 and the cyclooxygenase inhibitor diclofenac reduced pulmonary vascular reactions after LPS challenge. Based on the current data, we conclude that the pulmonary arterial pressure increase and edema formation after LPS injection are related to an ET-1- and TXA2-dependent mechanism.
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Antagonistas de los Receptores de Endotelina , Endotelina-1/sangre , Fenilpropionatos/farmacología , Presión Esfenoidal Pulmonar/efectos de los fármacos , Pirimidinas/farmacología , Tromboxano A2/sangre , Animales , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/farmacología , Endotelina-1/farmacología , Endotelina-1/fisiología , Femenino , Lipopolisacáridos/administración & dosificación , Masculino , Estudios Prospectivos , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiología , Conejos , Tromboxano A2/fisiologíaRESUMEN
OBJECTIVE: During systemic inflammation, elevated levels of endothelin (ET)-1 have been reported. The aim of this study was to investigate the effects of ET-1 on neutrophil (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from blood and tissues. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a university hospital. SUBJECTS: A total of 18 female chinchilla rabbits. INTERVENTIONS: To quantify the clearance process, defined numbers (10(8) colony-forming units) of E. coli were injected intravenously into anesthetized rabbits, 60 mins after onset of continuous 0.2 microg/kg/min ET-1 administration (n = 9) and after saline infusion (control group, n = 9), respectively. To evaluate potential effects of ET-1 on bacterial elimination and killing, blood clearance of E. coli and colonization of different organs were investigated. MEASUREMENTS: Variables monitored were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, blood gases, serum lactate concentrations, and nitrite and nitrate levels. The animals were killed 3 hrs after bacterial injection and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. MAIN RESULTS: Compared with the control group, ET-1 significantly impaired PMN respiratory burst (p < .05) and prolonged elimination of injected E. coli from the blood (p < .01), whereas phagocytosis functions remained unaltered. The reduced PMN burst activity after ET-1 was associated with a higher bacterial colonization of all organs (lung, p < .01; spleen, p < .05). Endothelin-1 induced increases in mean arterial pressure (p < .01) and serum lactate concentrations, whereas nitrite and nitrate levels remained unaltered. CONCLUSION: Endothelin-1 impairs respiratory burst and bacterial clearance from the blood and tissue. Thus, elevated levels of ET-1 during sepsis could induce organ hypoperfusion and cause disturbances in immune functions, increasing the risk of bacterial infections.
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Endotelina-1/farmacología , Infecciones por Escherichia coli/inmunología , Escherichia coli/inmunología , Neutrófilos/efectos de los fármacos , Estallido Respiratorio/efectos de los fármacos , Animales , Femenino , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/inmunología , Neutrófilos/inmunología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Conejos , Estallido Respiratorio/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: The most potent vasoconstrictor known, endothelin-1, is currently considered to mediate cerebral vasospasm in subarachnoid hemorrhage (SAH), which can cause delayed cerebral ischemia. In our study, we performed clinical and in vitro experiments to investigate the origin and the mechanisms of the secretion of endothelin-1 in SAH. METHODS: Endothelin-1 and markers of inflammatory host response (interleukin [IL]-1ss, IL-6, and tumor necrosis factor-alpha) were comparatively quantified in the cerebrospinal fluid (CSF) of SAH patients and control subjects, and concentrations were related to clinical characteristics. Furthermore, mononuclear leukocytes isolated from the CSF of SAH patients and control subjects were analyzed regarding their mRNA expression of endothelin-1 and inflammatory cytokines. Finally, complementary in vitro experiments were performed to investigate whether coincubation of blood and CSF can trigger leukocytic mRNA expression and release of these factors. RESULTS: Activated mononuclear leukocytes in the CSF of SAH patients synthesize and release endothelin-1 in parallel with known acute-phase reactants (IL-1ss, IL-6, and tumor necrosis factor-alpha). Complementary in vitro experiments not only further confirmed this leukocytic origin of endothelin-1 but also showed that aging and subsequent hemolysis of blood is sufficient to induce such endothelin-1 production. CONCLUSIONS: The demonstration that endothelin-1 is produced by activated CSF mononuclear leukocytes suggests that subarachnoid inflammation may represent a therapeutic target to prevent vasospasm and delayed cerebral ischemia after SAH.
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Proteínas de Fase Aguda/biosíntesis , Líquido Cefalorraquídeo/citología , Endotelina-1/sangre , Leucocitos/metabolismo , Hemorragia Subaracnoidea/sangre , Proteínas de Fase Aguda/análisis , Adulto , Anciano , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Endotelina-1/biosíntesis , Femenino , Humanos , Leucocitos/química , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeoRESUMEN
UNLABELLED: Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. HES solutions differ from each other with regard to molecular weight and mode of hydroxyl substitution (degree of hydroxylation, C2:C6 hydroxyethyl ratio, concentration), factors which may have varying effects on coagulation. We studied, in vitro, three different HES preparations (molecular weight/degree of hydroxylation/concentration/C2:C6 ratio of substitution 70.000/0. 5/6%/3.2; Pharmacia & Upjohn Co., Erlangen, Germany; 130.000/0. 4/6%/11.2 and 200.000/0.5/6%/4.6; Fresenius Co., Bad Homburg, Germany) and, for comparison, lactated Ringer's solution (RL) at 33% and 66% dilution with whole blood. The influence of hemodilution was measured by using routine laboratory variables and SONOCLOT (Sonoclot II Coagulation and Platelet Function Analyzer, Sienco Co.) analysis, using a viscoelastic test, on the cellular as well as on the plasmatic hemostatic system. For statistical analysis of quantitative data, we used nonparametric analysis of variance and adequate post hoc tests. Qualitative data were analyzed by using the nonparametric Kruskal-Wallis test. A P value below 0.05 was considered significant. In contrast to the control group with RL, the liquid phase of coagulation (activated clotting time) was slightly affected by the 33% diluted HES solutions. HES 70.000, 130. 000, and 200.000 interfered significantly with the early stage of coagulation as expressed by the clot rate (gel/fibrin formation). Clot maturation and speed of maturation (time to peak) were strongly affected by HES 70.000 at all grades of dilution. HES 130.000 showed a faster clot formation process compared with the other HES solutions. HES 130.000 diluted 33% showed a better clot retraction as compared with the other HES solutions. In conclusion, in vitro hemodilution comparing different medium molecular weight HES solutions reveals that HES 130.000 seems preferable regarding some aspects of clot formation and retraction. RL affected clot formation only minimally, except for the early activation of clotting, which was measured by a shortened activated clotting time. IMPLICATIONS: We investigated the effect of different hydroxyethyl starch (HES) solutions (70.000, 130.000, 200.000) on coagulation. Regarding clot formation and retraction, HES 130.000 had some advantages over the other tested HES solutions. Lactated Ringer's solution affected coagulation only minimally, except for the early stage of clot formation.
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Coagulación Sanguínea/efectos de los fármacos , Hemodilución , Derivados de Hidroxietil Almidón/farmacología , Soluciones Isotónicas/farmacología , Sustitutos del Plasma/farmacología , Viscosidad Sanguínea/efectos de los fármacos , Retracción del Coagulo , Recuento de Eritrocitos/efectos de los fármacos , Fibrinógeno/metabolismo , Hematócrito , Humanos , Técnicas In Vitro , Masculino , Peso Molecular , Tiempo de Tromboplastina Parcial , Recuento de Plaquetas/efectos de los fármacos , Pruebas de Función Plaquetaria , Lactato de Ringer , UltrasonidoRESUMEN
To reduce allogeneic blood transfusion requirements during extracorporeal membrane oxygenation (ECMO) we evaluated an autotransfusion device which processes and retransfuses erythrocytes of changed ECMO-systems. We studied 10 elective changes of ECMO-systems in 7 patients. Hemoglobin levels, the amount of retransfused autologous blood and of transfused allogeneic packed red blood cell units were documented within 48 h after the system change and compared to the measurements obtained from former ECMO-system changes without using any autotransfusion device. We determined the Horrowitz-index, Interleukin 6, 10, TNF-alpha and endothelin-I concentrations and coagulation parameters during the 48 hours after system change to study the compatibility of this procedure. Allogeneic blood transfusion was reduced from 7 to 2 units of packed red cells using the autotransfusion device. Additionally, no hints of any harmful side effects in these patients was observed.
Asunto(s)
Transfusión de Sangre Autóloga , Oxigenación por Membrana Extracorpórea/instrumentación , Adulto , Diseño de Equipo , Oxigenación por Membrana Extracorpórea/métodos , Hemoglobinas , Humanos , Interleucinas/sangre , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: The study was designed to investigate the effects of acetylcholine (ACh) on pulmonary circulation with special regard to mediators that could be involved in the mediation of ACh-induced effects. ACh has been reported to induce either vasodilation or vasoconstriction in the pulmonary circulation of different species. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Sixty-six adult rabbits of either sex. INTERVENTIONS: The experiments were performed on 66 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. ACh was injected in various concentrations after pulmonary artery preconstriction and in untreated lungs. MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. Perfusate samples were taken intermittently to determine endothelin-1 (ET-1), thromboxane A2 (TXA2), and prostacyclin (PGI2) concentrations. ACh in final dosages from 10(-5) to 10(-2) M (n = 6 each) was injected into the pulmonary artery of lungs treated with U46619 to induce pulmonary arterial hypertension or was injected into untreated lungs. To analyze the potential mechanisms of action, ACh (10(-5) M) was administered in additional experiments after pretreatment with either ETA receptor antagonist BQ123 (10(-6) M; n = 6) or the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6). In preconstricted pulmonary vessels, ACh (10(-3) and 10(-2) M) initially induced a PAP rise for 10 mins followed by a sustained decrease. In untreated lungs, ACh induced an immediate dose-dependent increase in PAP, requiring as long as 30 mins to return to predrug levels. Simultaneously, significantly elevated TXA2 and PGI2 levels were observed. Furthermore, ET-1 was detected in the perfusate, which was free from ET-1 before ACh administration. Pretreatment with BQ123 reduced substantially the ACh (10(-5) M)-induced PAP increase and the release of TXA2 and PGI2. At 5 mins, the PAP maximum was reduced from 18.5 +/- 3.2 mm Hg to 9.9 +/- 0.65 mm Hg by BQ123 pretreatment (p < .01). An inhibition of PAP increase was also observed after diclofenac pretreatment (11.6 +/- 0.4 mm Hg at 5 mins; p < .05). Inhibitory effects at 5 mins were significantly more pronounced in the BQ123 group compared with the diclofenac group. CONCLUSIONS: The effects of ACh on the pulmonary circulation of isolated rabbit lungs depend on ACh concentration and the basal tone of the arterial vasculature. In lungs with a normal pulmonary vascular resistance, ACh administration causes vasoconstriction via the release of ET-1 and TXA2, whereas vasodilation is induced in preconstricted pulmonary vessels.
Asunto(s)
Acetilcolina/fisiología , Acetilcolina/uso terapéutico , Endotelina-1/fisiología , Endotelina-1/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Circulación Pulmonar/efectos de los fármacos , Circulación Pulmonar/fisiología , Presión Esfenoidal Pulmonar/efectos de los fármacos , Presión Esfenoidal Pulmonar/fisiología , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Animales , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Antagonistas de los Receptores de Endotelina , Femenino , Hipertensión Pulmonar/inducido químicamente , Técnicas In Vitro , Masculino , Péptidos Cíclicos , Conejos , Tromboxano A2/fisiología , Resistencia Vascular/efectos de los fármacos , Resistencia Vascular/fisiología , VasoconstrictoresRESUMEN
Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ET(A) or ET(B) receptors, and vasorelaxation after ET-1 injection has been observed. Our study investigated the effects of ET-1 in isolated rabbit lungs, which were studied at basal tone (part I) and after preconstriction (U-46619; part II). Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. In part I, ET-1 (10(-8) M; n = 6; control) was injected after pretreatment with the ET(A)-receptor antagonist BQ-123 (10(-6) M; n = 6) or the ET(B)-receptor antagonist BQ-788 (10(-6) M; n = 6). The same protocol was carried out in part II after elevation of pulmonary vascular tone. ET-1 induced an immediate PAP increase (DeltaPAP 4.3 +/- 0.4 mmHg at 10 min) that was attenuated by pretreatment with BQ-123 (P < 0.05 at 10 min and P < 0.01 thereafter) and that was more pronounced after BQ-788 (P < 0.01 at 10 min and P < 0.001 thereafter). In part II, ET-1 induced an immediate rise in PAP with a maximum after 5 min (DeltaPAP 6.3 +/- 1.4 mmHg), leveling off at DeltaPAP 3.2 +/- 0.2 mmHg after 15 min. Pretreatment with BQ-123 failed to attenuate the increase. BQ-788 significantly reduced the peak pressure at 5 min (0.75 +/- 0.4 mmHg; P < 0.001) as well as the plateau pressure thereafter (P < 0.01). We conclude that ET-1 administration causes pulmonary vasoconstriction independent of basal vascular tone, and, at normal vascular tone, the vasoconstriction seems to be mediated via ET(A) receptors. BQ-788 treatment resulted in even more pronounced vasoconstriction. After pulmonary preconstriction, ET(A) antagonism exerted no effects on PAP, whereas ET(B) antagonism blocked the PAP increase. Therefore, ET-1-induced pulmonary vasoconstriction is shifted from an ET(A)-related to an ET(B)-mediated mechanism after pulmonary vascular preconstriction.
Asunto(s)
Endotelina-1/farmacología , Circulación Pulmonar/efectos de los fármacos , Receptores de Endotelina/fisiología , Vasoconstricción/efectos de los fármacos , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Vasos Sanguíneos/efectos de los fármacos , Femenino , Masculino , Oligopéptidos/farmacología , Péptidos Cíclicos/farmacología , Piperidinas/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiología , Conejos , Receptor de Endotelina A , Receptor de Endotelina B , Sistema Vasomotor/efectos de los fármacosRESUMEN
BACKGROUND: Severe pancreatitis is often complicated by shock and acute lung failure. Little is known about the pathophysiologic impact of the 16.6-kD lectine, named pancreatitis-associated protein (PAP), which is expressed during pancreatitis and which reduces mortality in a rat model with severe pancreatitis. Therefore, the aim of this study was to investigate the effects of PAP on the pulmonary vasculature after leukocyte activation with N-formyl-Met-Leu-Phe (fMLP). METHODS: The experiments were performed in buffer-perfused isolated rabbit lungs. Mean pulmonary artery pressure, weight gain, and thromboxane A2 synthesis of the lungs were monitored. PAP was obtained by affinity chromatography of pancreas juice from pancreatitic rats. The authors tested whether treatment with PAP (260 microg/l, n = 9; or 500 microg/l, n = 6) before fMLP injection (10(-6) M) influences mean pulmonary artery pressure and edema formation. Lungs that were treated only with fMLP (n = 6) served as controls. Additional experiments in which PAP was applied were performed to study whether PAP (260 microg/l, n = 3; 500 microg/l, n = 3; 1,000 microg/l, n = 3) itself effects lung vasculature. RESULTS: Application of fMLP resulted in an increase of mean pulmonary artery pressure (+/- SD) from 8 +/- 2 mmHg up to 26 +/-13 mmHg (P < 0.01) at a flow of 150 ml/min. Pretreatment with PAP reduced the peak pressure developed after fMLP to 15 +/- 7 mmHg (PAP 260 microg/l; P < 0.05) and to 9 +/- 4 mmHg (PAP 500 microg/l), respectively. In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration. In parallel to the attenuated pressure increase, thromboxane A2 release was significantly suppressed in the 260-microg/l (200 +/- 220 pmol x ml(-1) x min(-1); P < 0.01) and 500-microg/l (285 +/- 70 pmol x m(-1) x min(-1); P < 0.05) PAP groups compared with controls (1,138 +/- 800 pmol x ml(-1) x mi(-1)). Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release. CONCLUSION: Clinically relevant concentrations of PAP prevented fMLP-induced vasoconstriction and edema formation in the lung. These findings point toward a protective effect of PAP on polymorphonuclear neutrophil leukocyte-mediated lung injury.
Asunto(s)
Proteínas de Fase Aguda/uso terapéutico , Antígenos de Neoplasias , Biomarcadores de Tumor , Lectinas Tipo C , Leucocitos/patología , Edema Pulmonar/prevención & control , Vasoconstricción/efectos de los fármacos , Proteínas de Fase Aguda/aislamiento & purificación , Proteínas de Fase Aguda/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Cromatografía de Afinidad , Técnicas In Vitro , Pulmón/metabolismo , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacología , Activación Neutrófila , Tamaño de los Órganos/efectos de los fármacos , Proteínas Asociadas a Pancreatitis , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Circulación Pulmonar/efectos de los fármacos , Edema Pulmonar/patología , Edema Pulmonar/fisiopatología , Conejos , Ratas , Ratas Sprague-Dawley , Tromboxano A2/biosíntesis , Tromboxano B2/biosíntesisRESUMEN
As elevated endothelin-1 (ET-1) levels have been reported in systemic inflammatory diseases, the role of ET-1 as a promoter of inflammatory reactions is currently under investigation. The purpose of this study was to investigate the potential influence of ET-1 on systemic vascular pressure and immune function in terms of blood clearance and organ distribution of injected Escherichia coli in a rabbit model. To enable quantification of the clearance process, defined numbers of exogenous E. coli (10(8) cfu) were injected intravenously 60 min after starting the infusion of ET-1 (0.2 microgram kg-1 min-1; n = 9) or after saline infusion (controls, n = 9). Parameters monitored were arterial blood pressure, airway pressure, serum lactate concentrations and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were killed, and tissue samples of liver, kidney, spleen and lung were collected for bacterial counts. ET-1 infusion produced an increase in mean arterial pressure (83.9 +/- 3.9 mmHg vs. 50.1 +/- 4.1 mmHg at 120 min; P < 0.01) associated with higher serum lactate concentrations (12.6 +/- 1.3 vs. 5.4 +/- 0.3 mg dL-1; P < 0.001) and a delayed bacterial elimination from the blood compared with controls. Furthermore, there was increased colonization of the lungs (3.6 +/- 0.5 x 10(3) cfu vs. 745 +/- 120 cfu; P < 0.01), spleen (142.4 +/- 45.4 x 10(3) cfu vs. 227 +/- 5.2 x 10(3) cfu; P < 0.05) and kidney (758 +/- 329 vs. 357 +/- 151 cfu; NS), reflecting a reduced bacterial killing function.
Asunto(s)
Endotelina-1/fisiología , Infecciones por Escherichia coli/microbiología , Animales , Presión Sanguínea/efectos de los fármacos , Recuento de Colonia Microbiana , Endotelina-1/farmacología , Endotoxinas/metabolismo , Escherichia coli , Infecciones por Escherichia coli/sangre , Infecciones por Escherichia coli/fisiopatología , Femenino , Hemodinámica/efectos de los fármacos , Hemoglobinas/metabolismo , Riñón/efectos de los fármacos , Riñón/microbiología , Cinética , Ácido Láctico/sangre , Lipopolisacáridos/metabolismo , Hígado/efectos de los fármacos , Hígado/microbiología , Pulmón/efectos de los fármacos , Pulmón/microbiología , Masculino , Conejos , Bazo/efectos de los fármacos , Bazo/microbiologíaRESUMEN
OBJECTIVE: To examine the pathophysiologic role of vasoactive eicosanoids and endothelin-1 in granulocyte-mediated effects in the pulmonary vasculature. DESIGN: Prospective experimental study in rabbits. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty adult rabbits. INTERVENTIONS: The experiments were performed on 30 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. MEASUREMENTS AND MAIN RESULTS: The pulmonary arterial pressure and the lung weight gain were continuously registered. Intermittently perfused samples were taken to determine endothelin-1 and thromboxane A2 concentrations. Six experiments without intervention served as the sham group. The granulocytes in the pulmonary circulation were stimulated with N-formyl-L-leucin-methionyl-L-phenylalanine (FMLP; 10(-6) M; control, n = 6). To investigate whether activated granulocytes influence the pulmonary vasculature via endothelin-1, the endothelin-A receptor antagonist LU135252 (10(-6) M) was added to the perfusate before FMLP injection (n = 6). The potential involvement of thromboxane A2 in granulocyte-endothelial interaction was investigated by pretreatment with the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6). Activation of granulocytes resulted in an acute increase in pulmonary arterial pressure (>9 mm Hg), which was followed by a second delayed pressure increase after 60 mins (>14 mm Hg) and was paralleled by a massive generation of thromboxane A2 (>250 pg/ mL). Fifteen minutes after FMLP-injection, endothelin-1 was detectable in the perfusate. Pretreatment with the selective endothelin-A antagonist LU135252 significantly (p< .01) reduced the initial pressure response after FMLP stimulation, while diclofenac significantly reduced (p < .05) the delayed pressure increase. Using diclofenac (10 microg/mL) in conjunction with LU135252 (10(-6) M; n = 6) before FMLP injection significantly reduced the early and the delayed pressure increase. CONCLUSIONS: Activated granulocytes seem to enhance pulmonary vascular resistance via endothelin-1 and thromboxane A2. The endothelin-1 effects are probably mediated via endothelin-A receptors since the endothelin-A receptor antagonist LU135252 was able to suppress the early pressure reaction after FMLP injection, whereas the cyclooxygenase inhibitor diclofenac was able to reduce the second pressure increase.