Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning-A Translational Approach.

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%).

Melatonin pretreatment improves gastric mucosal blood flow and maintains intestinal barrier function during hemorrhagic shock in dogs.

OBJECTIVE: Melatonin improves hepatic perfusion after hemorrhagic shock and may reduce stress-induced gastric lesions. This study was designed to investigate whether pretreatment with melatonin may influence gastric mucosal microcirculatory perfusion (µflow), oxygenation (µHbO2 ), or intestinal barrier function during physiological and hemorrhagic conditions in dogs. METHODS: In a randomized crossover study, five anesthetized foxhounds received melatonin 100 µg kg-1 or vehicle (ethanol 5%) intravenously in the absence or presence of hemorrhagic shock (60 minutes, -20% blood volume). Systemic hemodynamic variables, gastric mucosal perfusion, and oxygenation were recorded continuously; intestinal barrier function was assessed intermittently via xylose absorption. RESULTS: During hemorrhagic shock, melatonin significantly attenuated the decrease in µflow, compared with vehicle (-19±9 vs -43±10 aU, P<.05), without influence on µHbO2 . A significant increase in xylose absorption was detected during hemorrhage in vehicle-treated dogs, compared with sham-operated animals (13±2 vs 8±1 relative amounts, P<.05); this was absent in melatonin-treated animals (6±1 relative amounts). Melatonin did not influence macrocirculation. CONCLUSIONS: Melatonin improves regional blood flow suggesting improved oxygen delivery in gastric mucosa during hemorrhagic shock. This could provide a mechanism for the observed protection of intestinal barrier function in dogs.

Melatonin or ramelteon therapy differentially affects hepatic gene expression profiles after haemorrhagic shock in rat--A microarray analysis.

BACKGROUND & AIMS: Melatonin has been demonstrated to reduce liver damage in different models of stress. However, there is only limited information on the impact of this hormone on hepatic gene expression. The aim of this study was, to investigate the influence of melatonin or the melatonergic agonist ramelteon on hepatic gene expression profiles after haemorrhagic shock using a whole genome microarray analysis. METHODS: Male Sprague-Dawley rats (200-300 g, n=4/group) underwent haemorrhagic shock (mean arterial pressure 35±5 mmHg). After 90 min of shock, animals were resuscitated with shed blood and Ringer's and treated with vehicle (5% dimethyl sulfoxide), melatonin or ramelteon (each 1.0 mg/kg intravenously). Sham-operated animals were treated likewise but did not undergo haemorrhage. After 2 h of reperfusion, the liver was harvested, and a whole genome microarray analysis was performed. Functional gene expression profiles were determined using the Panther® classification system; promising candidate genes were evaluated by quantitative polymerase chain reaction (PCR). RESULTS: Microarray and PCR data showed a good correlation (r(2)=0.84). A strong influence of melatonin on receptor mediated signal transduction was revealed using the functional gene expression profile analysis, whereas ramelteon mainly influenced transcription factors. Shock-induced upregulation of three candidate genes with relevant functions for hepatocytes (ppp1r15a, dusp5, rhoB) was significantly reduced by melatonin (p<0.05 vs. shock/vehicle), but not by ramelteon. Two genes previously known as haemorrhage-induced (il1b, s100a8) were transcriptionally repressed by both drugs. CONCLUSIONS: Melatonin and ramelteon appear to induce specific hepatic gene expression profiles after haemorrhagic shock in rats. The observed differences between both substances are likely to be attributable to a distinct mechanism of action in these agents.

Melatonin receptors mediate improvements of survival in a model of polymicrobial sepsis.

OBJECTIVES: Melatonin has been demonstrated to improve survival after experimental sepsis via antioxidant effects. Yet, recent evidence suggests that this protective capacity may also rely on melatonin receptor activation. Therefore, the present study was designed to investigate whether selective melatonin receptor-agonist ramelteon may influence survival and immune response in a model of polymicrobial sepsis in rats, wild-type and melatonin receptor MT1/MT2 double knockout mice. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats (200-250 g) and male C3H/HeN wild-type and MT1/MT2 receptor knockout mice (20-22 g). INTERVENTIONS: Animals underwent cecal ligation and incision and remained anesthetized for evaluation of survival for 12 hours (rats: n = 15 per group) or 15 hours (mice: n = 10 per group). Analysis of immune response by means of enzyme-linked immunosorbent assay was performed before and 5 hours after cecal ligation and incision (rats only; n = 5 per group). After induction of sepsis, animals were treated IV with vehicle, different doses of melatonin (rats: 0.01/0.1/1.0/10 mg/kg; mice: 1.0 mg/kg), ramelteon, melatonin receptor-antagonist luzindole, ramelteon + luzindole, or melatonin + luzindole (each 1.0 mg/kg). Sham controls underwent laparotomy but not cecal ligation and incision. MEASUREMENTS AND MAIN RESULTS: Compared with vehicle, administration of ramelteon or melatonin significantly improved median survival time in rats (sepsis/melatonin [0.1 mg/kg], 554 min, [1.0 mg/kg] 570 min, [10 mg/kg] 579 min; sepsis/ramelteon, 468 min; each p < 0.001 vs sepsis/vehicle, 303 min) and wild-type mice (sepsis/melatonin, 781 min; sepsis/ramelteon, 701 min; both p < 0.001 vs sepsis/vehicle, 435 min). This effect was completely antagonized by coadministration of luzindole in all groups. Melatonin, ramelteon, or luzindole had no significant effect on survival time in knockout mice. Significantly elevated concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-10 were observed 5 hours after cecal ligation and incision in rats (p < 0.05 vs baseline and corresponding sham); neither ramelteon nor melatonin treatment significantly affected immune response. CONCLUSIONS: Melatonin receptors mediate improvements of survival after polymicrobial sepsis in rats and mice; this effect appears to be independent from major alterations of cytokine release.

Intravenous propofol, ketamine (ketofol) and rocuronium after sevoflurane induction provides long lasting anesthesia in ventilated rats.

Rats are commonly used animals for laboratory experiments and many experiments require general anesthesia. However, the lack of published and reproducible intravenous anesthesia protocols for rats results in unnecessary animal use to establish new anesthesia techniques across institutions. We therefore developed an anesthesia protocol with propofol, ketamine, and rocuronium for mechanically ventilated rats, and evaluated vital parameters and plasma concentrations. 15 male Sprague-Dawley rats underwent inhalation induction with sevoflurane and tracheal, venous and arterial cannulation. After established venous access, sevoflurane was substituted by propofol and ketamine (ketofol). Rocuronium was added under mechanical ventilation for 7 h. Drug dosages were stepwise reduced to prevent accumulation. All animals survived the observation period and showed adequate depth of anesthesia. Mean arterial pressure and heart rate remained within normal ranges. Median propofol plasma concentrations remained stable: 1, 4, 7 h: 2.0 (interquartile range (IQR): 1.8-2.2), 2.1 (1.8-2.2), 1.8 (1.6-2.1) µg/ml, whereas median ketamine concentrations slightly differed after 7 h compared to 1 h: 1, 4, 7 h: 3.7 (IQR: 3.5-4.5), 3.8 (3.3-4.1), 3.8 (3.0-4.1) µg/ml. Median rocuronium plasma concentrations were lower after 4 and 7 h compared to 1 h: 1, 4, 7 h: 3.9 (IQR: 3.5-4.9), 3.2 (2.7-3.3), 3.0 (2.4-3.4) µg/ml. Our anesthesia protocol provides stable and reliable anesthesia in mechanically ventilated rats for several hours.

Obstructive sleep apnea syndrome is associated with overactive bladder and urgency incontinence in men.

STUDY OBJECTIVE: To investigate the incidence of overactive bladder (OAB) and urgency incontinence (UI) in men with obstructive sleep apnea syndrome (OSAS). DESIGN: Prospective questionnaire study SETTING: Saarland University Hospital PATIENTS: All male patients who underwent full-night in-laboratory polysomnography between November 2006 and April 2007. INTERVENTIONS: Overactive bladder symptom score (OABSS) and International Consultation on Incontinence Questionnaire, Short-Form (ICIQ-SF). MEASUREMENTS AND RESULTS: OSAS severity was assessed according to the apnea-hypopnea-index (AHI). Return rate of questionnaires was 100% (n=100). Patients with upper airway resistance syndrome (UARS) served as controls. Evaluation of OABSS revealed that patients with moderate and severe OSAS presented with a significantly higher incidence of symptoms of OAB than patients with mild OSAS and UARS (P<0.05). Further, the ICIQ-SF revealed a higher occurrence of UI in patients with severe OSAS than in those with mild OSAS and UARS (P<.05). CONCLUSIONS: Increasing severity of OSAS appears to be associated with an increasing occurrence of overactive bladder and urgency incontinence in men. This relationship may have clinical implications for the treatment of affected patients.

Endogenous and Exogenous Melatonin Exposure Attenuates Hepatic MT1 Melatonin Receptor Protein Expression in Rat.

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer's solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization.

Melatonin receptors mediate improvements of liver function but not of hepatic perfusion and integrity after hemorrhagic shock in rats.

OBJECTIVE: Melatonin has been demonstrated to attenuate organ damage in models of ischemia and reperfusion. Melatonin treatment before hemorrhagic shock has been shown to improve liver function and hepatic perfusion. Proposed mechanisms of the pineal hormone involve direct inactivation of reactive oxygen species and induction of antioxidative enzymes. However, recent evidence suggests a strong influence of melatonin receptor activation for these effects. Specific protection of organ function by melatonin after hemorrhage has not been investigated yet. In this study, we evaluated whether melatonin therapy after hemorrhagic shock improves liver function and hepatic perfusion, with emphasis on melatonin receptor activation. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats, 200-300 g (n = 10 per group). INTERVENTIONS: Animals underwent hemorrhagic shock (mean arterial pressure, 35 +/- 5 mm Hg for 90 mins) and were resuscitated with shed blood and Ringer's solution. At the end of shock, animals were treated with either melatonin (10 mg/kg, intravenously), melatonin receptor antagonist luzindole (2.5 mg/kg, intravenously) plus melatonin (10 mg/kg, intravenously), luzindole alone (2.5 mg/kg, intravenously), or vehicle. MEASUREMENTS AND MAIN RESULTS: After 2 hrs of reperfusion, either liver function was assessed by plasma disappearance rate of indocyanine green or intravital microscopy of the liver was performed for evaluation of hepatic perfusion, hepatocellular redox state, and hepatic integrity. Compared with vehicle controls, melatonin therapy after hemorrhagic shock significantly improved plasma disappearance rate of indocyanine green, hepatic redox state, hepatocellular injury, and hepatic perfusion index. Coadministration of luzindole completely abolished the protective effect with respect to liver function only, and improvements regarding hepatic redox state, perfusion, and integrity were comparable with melatonin treatment alone. CONCLUSIONS: Melatonin therapy after hemorrhagic shock improves liver function, hepatic perfusion, redox state, and hepatic integrity. With respect to liver function, beneficial effects of the pineal hormone seem to be dependent on melatonin receptor activation.

Selective activation of melatonin receptors with ramelteon improves liver function and hepatic perfusion after hemorrhagic shock in rat.

OBJECTIVE: Melatonin may attenuate organ damage via direct antioxidative properties, and was recently demonstrated to reduce cardiac and hepatic injury through receptor-dependent effects. However, the relevance of an isolated activation of melatonin receptors for organ protection, excluding direct antioxidant effects, has not been established yet. This study was designed to investigate whether therapy with melatonin receptor agonist and hypnotic substance ramelteon may improve liver function, hepatic perfusion, and hepatic integrity after hemorrhagic shock in rat. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 10 per group). INTERVENTIONS: Animals underwent hemorrhagic shock (mean arterial pressure 35 +/- 5 mm Hg for 90 mins) and were resuscitated with shed blood and Ringer's lactate (2 hrs). At the end of shock, animals were treated with ramelteon (1.0 mg/kg intravenously), melatonin receptor antagonist luzindole plus ramelteon (each 1.0 mg/kg intravenously), or vehicle. MEASUREMENTS AND MAIN RESULTS: In vitro, ramelteon displayed no relevant antioxidant capacity in an 2,2'-Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assay, compared with melatonin. In vivo, liver function was assessed by plasma disappearance rate of indocyanine green, and intravital microscopy was performed for evaluation of hepatic perfusion index, nicotinamide adenine dinucleotide phosphate autofluorescence, and hepatic integrity. Compared with vehicle controls, ramelteon therapy significantly improved plasma disappearance rate of indocyanine green (7.89 +/- 2.12% vs. 13.67 +/- 2.51%; p = 0.006), hepatic perfusion index (352.04 +/- 111.78 pl/sec/mm vs. 848.81 +/- 181.38 pl/sec/mm; p = 0.002), nicotinamide adenine dinucleotide phosphate autofluorescence and hepatocellular injury. Coadministration of luzindole abolished the protective effect of ramelteon with respect to liver function and nicotinamide adenine dinucleotide phosphate autofluorescence. CONCLUSIONS: Ramelteon therapy improves liver function, hepatic perfusion, and hepatocellular integrity after hemorrhagic shock in rat. This demonstrates that an isolated activation of melatonin receptors may be sufficient for organ protection, independent from direct antioxidant effects. The hypnotic ramelteon could thus play an interesting role in future sedation concepts for critical care patients.

Melatonin pretreatment improves liver function and hepatic perfusion after hemorrhagic shock.

Exogenous administration of pineal hormone melatonin (MEL) has been demonstrated to attenuate organ damage in models of I/R and inflammation by antioxidative effects. However, specific organ-protective effects of MEL with respect to hemorrhagic shock have not been investigated yet. In the present study, we evaluated the role of MEL pretreatment for hepatic perfusion, redox state, and function after hemorrhage and resuscitation, with emphasis on MEL receptor activation. In a model of hemorrhagic shock (MAP 35 +/- 5 mmHg for 90 min) and reperfusion (2 h), we measured nicotinamide adenine dinucleotide phosphate (reduced form; NADPH) autofluorescence, hepatic microcirculation, and hepatocellular injury by intravital microscopy, as well as plasma disappearance rate of indocyanine green (PDRICG) as a sensitive maker of liver function in rat. Pretreatment with 10 mg kg(-1) MEL (i.v.) 15 min before induction of hemorrhage resulted in a significantly improved PDR(ICG) compared with controls (MEL/shock, 15.02% min(-1) +/- 2.9 SD vs. vehicle/shock, 6.18 +/- 4.6 SD; P = 0.001). Intravital microscopy after reperfusion revealed an improved hepatic perfusion index, redox state, and reduced hepatocellular injury in pretreated animals compared with the vehicle group. Melatonin receptor antagonist luzindole (LZN; 2.5 mg kg(-1)) almost completely abolished the protective effects of MEL pretreatment with respect to liver function (MEL + LZN/shock PDR(ICG), 7.31% min(-1) +/- 3.4 SD). Beneficial effects regarding hepatic perfusion, redox state, and cellular injury were not influenced by LZN, indicating that they may depend on antioxidative effects of MEL. However, liver function after hemorrhage is effectively maintained by MEL pretreatment via receptor-dependent pathways.

The performance of six pulse oximeters in the environment of neuronavigation.

BACKGROUND: Although the use of pulse oximeters may be regarded a standard of care for monitoring anesthesia procedures, these monitors may be susceptible to various kinds of disturbances. Recently, it was suggested that neuronavigation equipment may interfere with pulse oximeter accuracy. In this study, we evaluated the effect of a neurosurgical image guidance system on the performance of six different pulse oximeters. Two simple shielding methods were evaluated. METHODS: Twenty healthy, adult, nonsmoking volunteers were equipped with six different pulse oximeters on both hands. Baseline values for heart rate, arterial oxygen saturation, and signal quality were assessed. After activation of the Brain Lab VectorVision Neuronavigation System, the effects on signal quality and saturation recognition were evaluated. Measurements were repeated using two different shielding techniques, a cotton blanket and aluminum sheets. RESULTS: Activation of the image guidance system resulted in a significant disturbance of signal quality and saturation detection, which was partially reversible by both shielding techniques. Significant differences were noted among the six brands of pulse oximeters for signal quality (P < 0.001) and saturation recognition (P < 0.001), and for the response to shielding methods (P < 0.001). Coverage of the probes with aluminum foil resulted an in undisturbed saturation recognition in all subjects with almost all monitors. CONCLUSIONS: Infrared pulse waves from neurosurgical navigation equipment may interfere with pulse oximeter measurements. Shielding the probe with aluminum foil sufficiently eliminated the infrared interference.

[The practice of postanesthesia visits - a questionnaire study]. / A prática de visitas pós­anestésicas ­ estudo de um questionário.

BACKGROUND AND OBJECTIVE: Regular postanesthesia visits allow the detection of anesthesia related complications and increase patient satisfaction. Consequently, the performance of postanesthesia visits has been recommended after certain types of anesthesia. However, no data is available concerning the current practice of postanesthesia visits. Therefore, this study was designed to investigate quantity, organization, contents, significance and problems of postanesthesia visits in Germany. METHODS: For this prospective closed-design survey, a questionnaire, consisting of 13 questions, was designed and tested for objectivity, reliability and validity. Subsequently, 3955 registered anesthesiologists were contacted via email to answer this survey. RESULTS: Return rate was 31.4%; 958 questionnaires were included in the study. Only a small portion of patients was estimated to receive a postanesthesia visit (median: 20.0%). In hospitals with a specific postanesthesia visit service, this number was significantly higher (median: 65.0%, p<0.001) vs. no postanesthesia visit service. Postanesthesia visits usually lasted less than 5minutes (60.0%), and were typically conducted on the day of surgery (48.0%), after regular working hours (55.0%). 38.0% of the respondents reported to detect perioperative complications intermittently during their visits. While 98.0% of all respondents believe that postanesthesia visits improve the quality of their own work, 86.0% of the participants complain a lack of time for this task. CONCLUSIONS: Our survey indicates that current working conditions prevent a regular postanesthesia visit routine. Considering the high appreciation of postanesthesia visits by anesthesiologists, as well as the relevant incidence of postoperative complications detected during these visits, it seems desirable to consider organizational improvements for postanesthesia care.

A change of colloid from hydroxyethyl starch to gelatin does not reduce rate of renal failure or mortality in surgical critical care patients: Results of a retrospective cohort study.

PURPOSE: Hydroxyethyl starch (HES) may compromise renal function in critically ill patients. As an alternative, gelatin (GEL) was suggested. This study investigated whether GEL (4%) may have advantages over HES (6%, 130/0.4) with respect to acute renal failure (ARF), length of intensive care unit /hospital stay, and 30-day mortality and evaluated dose-dependent effects. MATERIAL AND METHODS: We performed a retrospective cohort analysis of 1522 surgical intensive care patients in a single university hospital where HES was changed to GEL in June 2006. The year before, 515 patients received HES; the year after, 540 patients received GEL. Within both years, 497 patients received crystalloids (CRY) only. Fluid therapy was performed upon clinical judgment and did not follow a study protocol. RESULTS: There was no difference in ARF between HES and GEL (P=.292), but ARF was more frequent in both colloid cohorts compared with CRY (HES/GEL vs CRY, P<.05). Mortality and maximum daily dose of both HES (r=0.93) and GEL (r=0.93) were significantly correlated, but mortality and total amount of CRY or total fluid intake were not significantly correlated. Cumulative amounts of fluids given were significantly higher in both colloid groups compared with CRY only, and GEL was given in higher doses than HES. In both colloid cohorts, the need for renal replacement therapy and 30-day mortality were significantly higher, and intensive care unit and hospital stay was longer, compared with CRY. CONCLUSIONS: A change of colloid from HES to GEL did not reduce the rate of ARF or mortality in surgical critical care patients. Both colloids appear to have dose-dependent effects on renal function.

Dobutamine pretreatment improves survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat.

Dobutamine is recommended for the treatment of sepsis-related circulatory failure in international guidelines. Furthermore, dobutamine has been demonstrated to improve liver function and hepatic perfusion after experimental hemorrhagic shock. Yet, it is unknown whether dobutamine may also induce hepatoprotective effects in sepsis. This study was designed to investigate the effect of dobutamine on survival, hepatic function, and microcirculation after polymicrobial sepsis in rat. Under general anesthesia, male Sprague-Dawley rats (n = 25/group) underwent pretreatment with dobutamine (10 µg/kg per minute) in the presence or absence of ß1-receptor antagonist esmolol (500 µg/kg per minute), esmolol alone, or vehicle for 6 h, before induction of sepsis (cecal ligation and incision [CLI]). Sham-operated animals were treated likewise but underwent no CLI. Five hours after CLI, either liver function was assessed by plasma disappearance rate of indocyanine green (n = 5/group), or intravital microscopy was performed (n = 5/group) for evaluation of hepatic perfusion index and hepatic integrity (as propidium iodide-stained cells per field). Alternatively, survival time after induction of CLI was monitored under general anesthesia (n = 15/group). Compared with controls, dobutamine pretreatment significantly improved plasma disappearance rate of indocyanine green (13.8% ± 4.1% vs. 20.6% ± 4.6%; P = 0.029), hepatic perfusion index (275.0 ± 126.1 vs. 703.5 ± 177.4 pL/s per mm; P < 0.001), hepatocellular injury (22.2 ± 6.7 vs. 6.4 ± 3.1 cells per field; P < 0.001), and survival time (326 ± 20 vs. 603 ± 41 min; P < 0.001). Coadministration of esmolol abolished the protective effect of dobutamine completely. Our results indicate that pretreatment with dobutamine may improve survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat via ß1-adrenoceptor activation. Dobutamine could therefore play a relevant role for hepatoprotection under septic conditions.

The practice of postanesthesia visits - a questionnaire study / A prática de visitas pós-anestésicas - estudo de um questionário

Abstract Background and objective Regular postanesthesia visits allow the detection of anesthesia related complications and increase patient satisfaction. Consequently, the performance of postanesthesia visits has been recommended after certain types of anesthesia. However, no data is available concerning the current practice of postanesthesia visits. Therefore, this study was designed to investigate quantity, organization, contents, significance and problems of postanesthesia visits in Germany. Methods For this prospective closed-design survey, a questionnaire, consisting of 13 questions, was designed and tested for objectivity, reliability and validity. Subsequently, 3955 registered anesthesiologists were contacted via email to answer this survey. Results Return rate was 31.4%; 958 questionnaires were included in the study. Only a small portion of patients was estimated to receive a postanesthesia visit (median: 20.0%). In hospitals with a specific postanesthesia visit service, this number was significantly higher (median: 65.0%, p < 0.001) vs. no postanesthesia visit service. Postanesthesia visits usually lasted less than 5 minutes (60.0%), and were typically conducted on the day of surgery (48.0%), after regular working hours (55.0%). 38.0% of the respondents reported to detect perioperative complications intermittently during their visits. While 98.0% of all respondents believe that postanesthesia visits improve the quality of their own work, 86.0% of the participants complain a lack of time for this task. Conclusions Our survey indicates that current working conditions prevent a regular postanesthesia visit routine. Considering the high appreciation of postanesthesia visits by anesthesiologists, as well as the relevant incidence of postoperative complications detected during these visits, it seems desirable to consider organizational improvements for postanesthesia care.

Resumo Justificativa e objetivo As visitas regulares pós-anestesia (VPA) permitem detectar complicações relacionadas à anestesia e aumentar a satisfação do paciente. Portanto, a VPA é recomendada após certos tipos de anestesia. Porém, não há dados disponíveis sobre a prática atual de VPA. Logo, este estudo foi projetado para investigar a quantidade, a organização, o conteúdo, a significância e os problemas da VPA na Alemanha. Método Para esta pesquisa de natureza fechada e prospectiva, um questionário com 13 perguntas foi criado e testado para identificar a objetividade, confiabilidade e validade. Posteriormente, 3.955 anestesiologistas registrados foram contatados via e-mail para responder a pesquisa. Resultados A taxa de retorno foi de 31,4%; 958 questionários foram incluídos no estudo. Apenas uma pequena parte dos pacientes foi designada para receber uma VPA (mediana: 20%). Em hospitais com serviço específico de VPA, esse número foi significativamente maior (mediana: 65%, p < 0,001) vs. ausência de serviço de VPA. As VPA normalmente duraram menos de cinco minutos (60%) e foram tipicamente conduzidas no dia da cirurgia (48%), após o turno normal de trabalho (55%). Dentre os que responderam o questionário, 38% relataram detectar complicações perioperatórias de forma intermitente durante as visitas. Enquanto 98% dos entrevistados acreditam que as VPA melhoram a qualidade de seu próprio trabalho, 86% se queixam de falta de tempo para essa tarefa. Conclusões Nossa pesquisa indica que as condições atuais de trabalho impedem a feitura rotineira de VPA. Considerando a alta valorização das VPA por anestesiologistas, bem como a incidência relevante de complicações no pós-operatório detectadas durante essas visitas, parece desejável considerar melhorias organizacionais para a assistência após a anestesia.

Hepatoprotective actions of melatonin: possible mediation by melatonin receptors.

Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone's intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin's influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.