Serum heparan sulfate levels are elevated in endotoxemia.

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

Isoflurane inhalation after induction of endotoxemia in rats attenuates the systemic cytokine response.

BACKGROUND/AIMS: Volatile anesthetics are frequently utilized in clinical routine. Isoflurane has been shown to attenuate the response to inflammatory stimuli such as lipopolysaccharide (LPS) when administered before induction of endotoxemia. We aimed therefore to evaluate the effect of isoflurane after administration of LPS on the cytokine release as a therapeutic option. MATERIALS AND METHODS: 21 male Sprague-Dawley rats were randomly assigned to the following groups: animals that received LPS (5 mg/kg, i.v.) without further intervention (LPS group), animals that received continuous inhalation of 1 minimum alveolar concentration (MAC) isoflurane 15 min after administration of LPS (Iso group) and no specific intervention (sham group). Four hours following LPS injection, plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6 and IL-10 were determined. Furthermore, nitrite release from cultured alveolar macrophages was analyzed. RESULTS: Inhalation of isoflurane after induction of endotoxemia attenuated the release of TNF-alpha (-52%, p < 0.05) and IL-1 beta (-39%, p < 0.05) as compared to the LPS group, while IL-6 and IL-10 levels were not significantly altered. Nitrite release was significantly increased in the Iso group as compared to the LPS group (+115%, p < 0.05). CONCLUSION: Inhalation of 1 MAC isoflurane after induction of endotoxemia in rats attenuates the systemic release of proinflammatory cytokines and concurrently enhances the production of nitrite in cultured alveolar macrophages.

Anti-inflammatory effects of sevoflurane and mild hypothermia in endotoxemic rats.

BACKGROUND: Volatile anesthetics and hypothermia attenuate the inflammatory response. We aimed to compare the anti-inflammatory effects of sevoflurane and mild hypothermia during experimental endotoxemia in the rat. METHODS: Anesthetized, ventilated Sprague-Dawley (SD) rats were randomly treated as follows (n = 6 per group): lipopolysaccharide (LPS) only, animals received LPS [LPS 5 mg/kg, intravenously (i.v.)] with no further treatment. In the LPS-hypothermia group, rats were cooled down to a temperature of 33 degrees C 15 min after LPS-injection (LPS 5 mg/kg i.v.). In animals of the LPS-sevoflurane group, sevoflurane inhalation (1 MAC) was initiated 15 min after induction of endotoxemia. The LPS-sevoflurane-hypothermia group received combined sevoflurane and hypothermia 15 min after induction of endotoxemia. A Sham group served as control without endotoxemia or treatment. After 4 h of endotoxemia, plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-10 were measured. Alveolar macrophages (AM) were ex vivo cultured for nitrite assay. RESULTS: Inhalation of sevoflurane significantly attenuated plasma levels of TNF-alpha (-60%, P < 0.05) and IL-1beta (-68%, P < 0.05) as compared with the LPS-only group. Hypothermia and its combination with sevoflurane significantly reduced TNF-alpha levels (-46% and -58%, each P < 0.05), but not IL-1beta. Application of mild hypothermia and also its combination with sevoflurane resulted in a significant increase in plasma IL-10 as compared with endotoxemic controls. Nitrite release from AM was found to be significantly suppressed by sevoflurane (-83%), hypothermia (-73%) and by the combination of both (-67%) (P < 0.05, each). CONCLUSION: Our data suggest that sevoflurane and mild hypothermia attenuate the inflammatory response during endotoxemia in vivo thus contributing to their beneficial role in clinical organ protection.

The beta-adrenoceptor antagonist propranolol counteracts anti-inflammatory effects of isoflurane in rat endotoxemia.

BACKGROUND: Recent studies suggest that volatile anaesthetics have anti-inflammatory and preconditioning properties and that beta-adrenoceptors are involved in the signalling pathways for these effects. Concurrently, the blockade of beta-adrenoceptors has been shown to augment the release of inflammatory mediators in response to pro-inflammatory stimuli. We therefore aimed to investigate whether the beta-adrenoceptor antagonist propranolol might modulate the anti-inflammatory effects of isoflurane on the systemic and pulmonary release of pro-inflammatory cytokines in endotoxemic rats. METHODS: Forty anaesthetized and ventilated Sprague-Dawley rats were randomly treated as follows. Lipopolysaccharide (LPS) only (n = 8), endotoxemia with LPS [5 mg/kg, intravenously (i.v.)]. LPS-isoflurane (n = 8): endotoxemia and continuous inhalation of 1 minimum alveolar concentration (MAC) of isoflurane. LPS-isoflurane-propranolol (n = 8): administration of propranolol (3 mg/kg) before continuous inhalation of isoflurane and induction of endotoxemia. LPS-propranolol (n = 8): administration of propranolol (3 mg/kg) before endotoxemia without inhalation of isoflurane. Sham (n = 8): control-group only with surgical preparation. After 4 h of endotoxemia, levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-10 (IL-10) in plasma and bronchoalveolar fluid (BALF) were analysed. Release of nitric oxide (NO) and amount of inducible nitric oxide synthase (iNOS) protein in alveolar macrophages was measured by Griess assay or determined by Western Blotting, respectively. RESULTS: Inhalation of isoflurane reduced the release of TNF-alpha (P < 0.05) and IL-1beta (P < 0.05) in plasma and IL-1beta (P < 0.05) in BALF. Co-administration of propranolol significantly inhibited these effects. During inhalation of isoflurane, the increased release of NO and iNOS protein from alveolar macrophages was also completely inhibited by propranolol. CONCLUSION: Our results indicate for the first time, that blockade of beta-adrenoceptors counteracts the anti-inflammatory effects of isoflurane in endotoxemic rats.

The effect of inhaled nitric oxide and inhaled iloprost on hypoxaemia in a patient with pulmonary hypertension after pulmonary thrombarterectomy.

Acute pulmonary hypertension with life-threatening right heart failure may complicate the postoperative course following cardiothoracic surgery. Both inhaled nitric oxide and inhaled iloprost, a stable analogue of prostacyclin, have been used frequently for this purpose in acute pulmonary hypertension of various origins. We present a case of a patient with acute pulmonary hypertension and severely impaired gas exchange following pulmonary thrombo-endarterectomy. Therapy with one inhaled vasodilator alone did not satisfactorily abort a postoperative pulmonary hypertensive crisis and low-output syndrome due to right heart failure. Combined inhaled nitric oxide and inhaled iloprost, however, showed additive effects. Hence, the combination of both drugs may be reasonable in cases where the standard therapy fails. The effect has been demonstrated by means of continuous blood gas monitoring.

[Videolaryngoscopy versus direct laryngoscopy for elective endotracheal intubation]. / Videolaryngoskopie versus direkte Laryngoskopie zur elektiven endotrachealen Intubation.

BACKGROUND: We compared the ease of viewing the glottis under direct vision during conventional laryngoscopy with the quality of indirectly viewing on a monitor during laryngoscopy with a Macintosh videolaryngoscope in a multicenter study. PATIENTS AND METHODS: After ethical approval and written informed consent of 300 patients with no anticipated difficult airway, conventional laryngoscopy with a Macintosh videolaryngoscopy blade was performed and the quality of the view of the glottis was assessed and documented according to the Cormack and Lehane scoring system as modified by Yentis and Lee. Subsequently, the indirect viewing conditions on the monitor were documented without changing the position of the blade. Differences between both distributions were analyzed using the Bland-Altman Test. RESULTS: Videolaryngoscopy improved the laryngoscopy score by 1 grade in 72 cases, by 2 grades in 17 cases and by 3 grades in 2 cases. A relevant improvement (from grades III/IV to II) was found in 28 patients. Viewing conditions worsened in 3 cases by 1 grade, in 4 cases by 2 grades and in 3 cases by 3 grades. A statistical analysis of the data gave a bias of 0.31 and an SD bias of 0.77.The 95% confidence interval of the distribution ranged from -1.12 to 1.81. CONCLUSION: Videolaryngoscopy can lead to better viewing conditions but in rare cases it may result in worse viewing conditions.

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility.

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular (RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng.kg(-1).min(-1)) and, consecutively, ILO (60 ng.kg(-1).min(-1)) for 20 min each. We measured pulmonary artery pressure (PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E(es)). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E(es) was enhanced during all doses tested, which reached statistical significance during EPO(25 ng) and ILO, but not during EPO(50 ng). PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function.

Inhaled nitric oxide induces cerebrovascular effects in anesthetized pigs.

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

Evaluation of a passive hemagglutination assay as screening test and of a recombinant immunoblot as confirmatory test for serological diagnosis of Lyme disease.

In order to evaluate a commercially available passive hemagglutination assay (PHA) as a screening test for the diagnosis of Lyme disease, 173 sera were tested by PHA and the results compared with those obtained by an indirect immunofluorescence assay (IFA) and a conventional immunoblot using whole cell antigen (IB). Identical results were found by PHA and IFA in 80% of all cases. The sensitivity of the PHA was comparable to that of the IB (96%). However, confirmation of positive PHA results was necessary due to lack of specificity. A commercially available recombinant immunoblot (RIB) was compared to a conventional IB for its efficiency as a confirmatory assay. The rate of agreement was 86% of 64 sera tested positive or negative by IB. However, in order to obtain this high concordance of the RIB and IB, it was necessary to modify the RIB interpretation criteria of the manufacturer. Thus, screening of serum specimens by the PHA and confirmation of test results by the RIB appears to be a convenient test combination that allows the serological diagnosis of Lyme disease in most cases.