Kim A. Boost

Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury

BACKGROUND High-pressure ventilation induces barotrauma and pulmonary inflammation, thus leading to ventilator-induced lung injury (VILI). By limiting the pulmonal inflammation cascade the anti-inflammatory cytokine interleukin (IL)-10 may have protective effects. Via inhalation, IL-10 reaches the pulmonary system directly and in high concentrations. METHODS Thirty six male, anesthetized and mechanically ventilated Sprague-Dawley rats were randomly assigned to the following groups (n=9, each): SHAM: pressure controlled ventilation with p(max)=20cmH(2)O, PEEP=4; VILI: ventilator settings were changed for 20min to p(max)=45cmH(2)O, PEEP=0; IL-10(high): inhalation of 10microg/kg IL-10 prior to induction of VILI; and IL-10(low): inhalation of 1microg/kg IL-10 prior to induction of VILI. All groups were ventilated and observed for 4h. RESULTS High-pressure ventilation increased the concentrations of macrophage inflammatory protein (MIP)-2 and IL-1beta in bronchoalveolar lavage fluid (BALF) and plasma. This effect was reduced by the inhalation of IL-10 (10microg/kg). Additionally, IL-10 increased the animal survival time (78% vs. 22% 4-h mortality rate) and reduced NO-release from ex vivo cultured alveolar macrophages. Moreover, VILI-induced pulmonary heat shock protein-70 expression was reduced by IL-10 aerosol in a dose-dependent manner. Similarly, the activation of matrix metalloproteinase (MMP)-9 in BALF was reduced dose-dependently by IL-10. IL-10-treated animals showed a lower macroscopic lung injury score and less impairment of lung integrity and gas exchange. CONCLUSIONS Prophylactic inhalation of IL-10 improved survival and reduced lung injury in experimental VILI. Results indicate that this effect may be mediated by the inhibition of stress-induced inflammation and pulmonary biotrauma.

IFN-gamma Impairs Release of IL-8 by IL-1beta-stimulated A549 Lung Carcinoma Cells

BackgroundProduction of interferon (IFN)-γ is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNγ on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells.MethodsA549 cells were cultured and stimulated with interleukin (IL)-1β alone or in combination with IFNγ. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA). mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA), respectively. Expression of inhibitor-κ Bα, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis.ResultsHere we demonstrate that IFNγ efficiently reduced IL-8 secretion under the influence of IL-1β. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNγ on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNγ on IL-1β-induced NF-κB activation as assessed by cellular IκB levels. Moreover, analysis of intracellular IL-8 suggests that IFNγ modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1β-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNγ indicating that modulation of IL-1β action by this cytokine displays specificity.ConclusionData presented herein agree with an angiostatic role of IFNγ as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1)-like functions in lung cancer patients e.g. by local delivery of IFNγ may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8.

Comparing hemodynamics, blood gas analyses and proinflammatory cytokines in endotoxemic and severely septic rats

Lipopolysaccharide (LPS) is often used in short-term models of inflammation. Since endotoxemia and sepsis are different entities we have recently established a short-term sepsis model in rats induced by cecal ligation and incision (CLI). This retrospective study was conducted in order to identify similarities and differences between both experimental approaches. 32 anesthetized/ventilated male rats from the following four groups were analysed (each n=8): CTRL-group (0.9% NaCl i.v.); LPS-group (5mg/kg i.v.); SHAM-group (laparotomy); CLI-group (1.5 cm blade incision). Mean arterial blood pressure (MAP) and blood gas parameters (arterial base excess (BE) and pH) were continuously recorded. Total observation time was 300 min. Plasma samples were obtained afterwards. LPS and CLI induced significant arterial hypotension and metabolic acidosis compared to CTRL- or SHAM-group, respectively. Yet, between the LPS- and CLI-groups, there were no differences in MAP, BE and pH. LPS significantly induced IL-1β, IL-6 and TNF-α in the plasma. In contrast, CLI showed a clear tendency towards increased IL-1β and IL-6 plasma levels and did not affect TNF-α. Our results indicate that the CLI sepsis model is suitable for short-term investigations on hemodynamic alterations and blood gas analyses during sepsis. 300 min after the proinflammatory insult, plasma concentrations of IL-1β and IL-6 in the plasma remain considerably lower after CLI compared to endotoxemia. Low TNF-α concentrations 300 min after sepsis induction could be interpreted as considerable immunosuppression during CLI sepsis.

Dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia.

Purpose To evaluate the prevalence of dual platelet inhibition in cases of severe retrobulbar hemorrhage following retrobulbar and peribulbar anesthesia. Setting Department of Ophthalmology, Ludwig‐Maximilans Universität, München, Germany. Design Retrospective study. Methods Two groups of patients were screened retrospectively over a 5‐year period for the inclusion criterion of severe retrobulbar hematoma after retrobulbar or parabulbar injection. The first group consisted of emergency cases referred to the clinic. A second group of patients had received retrobulbar block at the hospital. All cases were collected and screened for the presence of antiplatelet therapy. Results Among roughly 160 000 patient records screened, 3 patients with grade IV retrobulbar hematoma were identified. Two of these patients were taking dual antiplatelet medications and 2 were on anticoagulation therapy during the time of retrobulbar or peribulbar anesthesia. None of the cases showed single medication platelet inhibition. The visual acuity of all patients stayed low at the 6‐month follow‐up (1.2 logMAR in 1 patient and no light perception in 2 patients). Conclusions Retrobulbar hematoma is a rare but severe complication of retrobulbar anesthesia. With the high prevalence of dual platelet inhibition found in these cases, a prospective controlled trial seems unethical. In these high‐risk patients, surgery should be performed under topical anesthesia if possible or general anesthesia if necessary. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

23-Gauge-Pars-plana-Vitrektomien in Allgemeinanästhesie

PURPOSE Some studies have shown a significant reduction of postoperative pain by additional regional anesthesia in 20-gauge pars plana vitrectomy (20-G-ppV) with the patient under general anesthesia (AN). This observational study examined whether the advantages of additional retrobulbar anesthesia can also be observed with 23-gauge vitrectomy in AN. MATERIAL AND METHODS Surgery was performed in 130 patients under AN of which 88 received an additional retrobulbar block (group AN+) and 42 patients were treated without additional injection of retrobulbar anesthesia (group AN) using bupivacaine 0.5 % and mepivacaine 1%. The AN was performed with fentanyl and propofol. Postoperatively, the subjective patient pain was recorded using a numeric scale and the use and amount of analgesic drugs in the postoperative course were monitored. RESULTS The mean age of the patients was 53.6 ± 16.8 years, 52.6% of the patients were male, 31.5% were staged as American Society of Anesthesiologists (ASA) level I, 52.3% as ASA II and 15.4% as ASA III. At no time did the study show a statistically significant difference in pain frequency, intensity and analgesic consumption. However, the results suggest that patients in the AN+ group tended to experienced delayed and more intense postoperative pain, which is also reflected in the postoperative use of pain relief medications. CONCLUSIONS This study did not show any advantage by additional retrobulbar anesthesia regarding postoperative analgesia compared to an adequate treatment with peripheral acting analgesics during surgery and the early postoperative period.

[A 23-gauge pars plana vitrectomy after induction of general anesthesia: effect of additional retrobulbar anesthesia on postoperative pain].

PURPOSE Some studies have shown a significant reduction of postoperative pain by additional regional anesthesia in 20-gauge pars plana vitrectomy (20-G-ppV) with the patient under general anesthesia (AN). This observational study examined whether the advantages of additional retrobulbar anesthesia can also be observed with 23-gauge vitrectomy in AN. MATERIAL AND METHODS Surgery was performed in 130 patients under AN of which 88 received an additional retrobulbar block (group AN+) and 42 patients were treated without additional injection of retrobulbar anesthesia (group AN) using bupivacaine 0.5 % and mepivacaine 1%. The AN was performed with fentanyl and propofol. Postoperatively, the subjective patient pain was recorded using a numeric scale and the use and amount of analgesic drugs in the postoperative course were monitored. RESULTS The mean age of the patients was 53.6 ± 16.8 years, 52.6% of the patients were male, 31.5% were staged as American Society of Anesthesiologists (ASA) level I, 52.3% as ASA II and 15.4% as ASA III. At no time did the study show a statistically significant difference in pain frequency, intensity and analgesic consumption. However, the results suggest that patients in the AN+ group tended to experienced delayed and more intense postoperative pain, which is also reflected in the postoperative use of pain relief medications. CONCLUSIONS This study did not show any advantage by additional retrobulbar anesthesia regarding postoperative analgesia compared to an adequate treatment with peripheral acting analgesics during surgery and the early postoperative period.

23-Gauge-Pars-plana-Vitrektomien in Allgemeinanästhesie@@@A 23-gauge pars plana vitrectomy after induction of general anesthesia: Effekt einer additiven Retrobulbäranästhesie auf das postoperative Schmerzempfinden@@@Effect of additional retrobulbar anesthesia on postoperative pain

PURPOSE Some studies have shown a significant reduction of postoperative pain by additional regional anesthesia in 20-gauge pars plana vitrectomy (20-G-ppV) with the patient under general anesthesia (AN). This observational study examined whether the advantages of additional retrobulbar anesthesia can also be observed with 23-gauge vitrectomy in AN. MATERIAL AND METHODS Surgery was performed in 130 patients under AN of which 88 received an additional retrobulbar block (group AN+) and 42 patients were treated without additional injection of retrobulbar anesthesia (group AN) using bupivacaine 0.5 % and mepivacaine 1%. The AN was performed with fentanyl and propofol. Postoperatively, the subjective patient pain was recorded using a numeric scale and the use and amount of analgesic drugs in the postoperative course were monitored. RESULTS The mean age of the patients was 53.6 ± 16.8 years, 52.6% of the patients were male, 31.5% were staged as American Society of Anesthesiologists (ASA) level I, 52.3% as ASA II and 15.4% as ASA III. At no time did the study show a statistically significant difference in pain frequency, intensity and analgesic consumption. However, the results suggest that patients in the AN+ group tended to experienced delayed and more intense postoperative pain, which is also reflected in the postoperative use of pain relief medications. CONCLUSIONS This study did not show any advantage by additional retrobulbar anesthesia regarding postoperative analgesia compared to an adequate treatment with peripheral acting analgesics during surgery and the early postoperative period.