CXCR2 in acute lung injury.

In pulmonary inflammation, recruitment of circulating polymorphonuclear leukocytes is essential for host defense and initiates the following specific immune response. One pathological hallmark of acute lung injury and acute respiratory distress syndrome is the uncontrolled transmigration of neutrophils into the lung interstitium and alveolar space. Thereby, the extravasation of leukocytes from the vascular system into the tissue is induced by chemokines that are released from the site of inflammation. The most relevant chemokine receptors of neutrophils are CXC chemokine receptor (CXCR) 1 and CXCR2. CXCR2 is of particular interest since several studies implicate a pivotal role of this receptor in development and promotion of numerous inflammatory disorders. CXCR2 gets activated by ELR(+) chemokines, including MIP-2, KC (rodents) and IL-8 (human). Since multiple ELR(+) CXC chemokines act on both receptors--CXCR1 and CXCR2--a pharmacologic agent blocking both receptors seems to be advantageous. So far, several CXCR1/2 antagonists have been developed and have been tested successfully in experimental studies. A newly designed CXCR1 and CXCR2 antagonist can be orally administered and was for the first time found efficient in humans. This review highlights the role of CXCR2 in acute lung injury and discusses its potential as a therapeutic target.

[Anesthesia and bariatric surgery]. / Anästhesie bei bariatrischer Chirurgie.

Today obesity is accepted as an independent disease. The WHO describes obesity as an epidemic disease occurring worldwide and associated comorbidities affect all organ systems. Bariatric operations lead to an improvement or even complete remission of obesity-correlated comorbidities. Bariatric operations are conducted as restrictive, malabsorptive, or mixed procedures. The preoperative anesthetic evaluation of comorbidities is carried out with a special focus on preexisting impairments of cardiac and lung function (e.g. cardiomyopathy, obstructive respiratory dysfunctions). Extremely obese patients are at risk of aspiration. Airway management at anesthesia induction includes normal intubation or, if additional risk factors are present, either fiber optic awake intubation or rapid sequence induction. The pharmacokinetics of all applicable drugs are altered in extremely obese patients and they are at risk for developing postoperative thromboembolic complications with a high mortality rate. Therefore early and sufficient thrombotic prophylaxis is important.

[Mastocytosis. A challenge in anaesthesiology]. / Mastozytose. Herausforderung in der Anästhesie.

Mastocytosis is a general term for a heterogeneous group of rare disorders. Many agents used in anaesthesia can trigger mast cell degranulation with release of histamine, prostaglandin, tryptase and heparin. Therefore, patients with mastocytosis are high-risk patients when undergoing anaesthesia. The management of these patients in anaesthesia will be discussed on the basis of the literature and illustrated with the discussion of three case reports. A premedication with antihistamines and a glucocorticoid is recommended. For induction of general anaesthesia propofol, etomidate, ketamine, a fentanyl-type opioid, cis-atracurium or pancuronium are recommended. Anaesthesia can be maintained either by a total intravenous technique or with a volatile anaesthetic such as sevoflurane.

Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation.

Heme oxygenase-1 (HO-1) has been shown to display anti-inflammatory properties in models of acute pulmonary inflammation. For the first time, we investigated the role of leukocytic HO-1 using a model of HO-1(flox/flox) mice lacking leukocytic HO-1 that were subjected to lipopolysaccharide (LPS)-induced acute pulmonary inflammation. Immunohistology and flow cytometry demonstrated that activation of HO-1 using hemin decreased migration of polymorphonuclear leukocytes (PMNs) to the lung interstitium and bronchoalveolar lavage (BAL) in the wild-type and, surprisingly, also in HO-1(flox/flox) mice, emphasizing the anti-inflammatory potential of nonmyeloid HO-1. Nevertheless, hemin reduced the CXCL1, CXCL2/3, tumor necrosis factor-α (TNFα), and interleukin 6 (IL6) levels in both animal strains. Microvascular permeability was attenuated by hemin in wild-type and HO-1(flox/flox) mice, indicating a crucial role of non-myeloid HO-1 in endothelial integrity. The determination of the activity of HO-1 in mouse lungs revealed no compensatory increase in the HO-1(flox/flox) mice. Topical administration of hemin via inhalation reduced the dose required to attenuate PMN migration and microvascular permeability by a factor of 40, emphasizing its clinical potential. In addition, HO-1 stimulation was protective against pulmonary inflammation when initiated after the inflammatory stimulus. In conclusion, nonmyeloid HO-1 is crucial for the anti-inflammatory effect of this enzyme on PMN migration to different compartments of the lung and on microvascular permeability.