Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury.

Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H2S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H2S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H2S pretreatment. Moreover, H2S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1ß in the alveolar space. In vitro, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H2S. Taken together, we provide first evidence that H2S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H2S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H2S pretreatment ameliorates LPS-induced ALI.

Increasing arterial oxygen partial pressure during cardiopulmonary resuscitation is associated with improved rates of hospital admission.

AIM: As recent clinical data suggest a harmful effect of arterial hyperoxia on patients after resuscitation from cardiac arrest (CA), we aimed to investigate this association during cardiopulmonary resuscitation (CPR), the earliest and one of the most crucial phases of recirculation. METHODS: We analysed 1015 patients who from 2003 to 2010 underwent out-of-hospital CPR administered by emergency medical services serving 300,000 inhabitants. Inclusion criteria for further analysis were nontraumatic background of CA and patients >18 years of age. One hundred and forty-five arterial blood gas analyses including oxygen partial pressure (paO2) measurement were obtained during CPR. RESULTS: We observed a highly significant increase in hospital admission rates associated with increases in paO2 in steps of 100 mmHg (13.3 kPa). Subsequently, data were clustered according to previously described cutoffs (≤ 60 mmHg [8 kPa]], 61-300 mmHg [8.1-40 kPa], >300 mmHg [>40 kPa]). Baseline variables (age, sex, initial rhythm, rate of bystander CPR and collapse-to-CPR time) of the three compared groups did not differ significantly. Rates of hospital admission after CA were 18.8%, 50.6% and 83.3%, respectively. In a multivariate analysis, logistic regression revealed significant prognostic value for paO2 and the duration of CPR. CONCLUSION: This study presents novel human data on the arterial paO2 during CPR in conjunction with the rate of hospital admission. We describe a significantly increased rate of hospital admission associated with increasing paO2. We found that the previously described potentially harmful effects of hyperoxia after return of spontaneous circulation were not reproduced for paO2 measured during CPR. CLINICAL TRIAL REGISTRATION: n/a.

Image fusion analysis of (99m)Tc-HYNIC-Tyr(3)-octreotide SPECT and diagnostic CT using an immobilisation device with external markers in patients with endocrine tumours.

PURPOSE: The aim of this study was to assess the value of multimodality imaging using a novel repositioning device with external markers for fusion of single-photon emission computed tomography (SPECT) and computed tomography (CT) images. The additional benefit derived from this methodological approach was analysed in comparison with SPECT and diagnostic CT alone in terms of detection rate, reliability and anatomical assignment of abnormal findings with SPECT. METHODS: Fifty-three patients (30 males, 23 females) with known or suspected endocrine tumours were studied. Clinical indications for somatostatin receptor (SSTR) scintigraphy (SPECT/CT image fusion) included staging of newly diagnosed tumours (n=14) and detection of unknown primary tumour in the presence of clinical and/or biochemical suspicion of neuroendocrine malignancy (n=20). Follow-up studies after therapy were performed in 19 patients. A mean activity of 400 MBq of (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide was given intravenously. SPECT using a dual-detector scintillation camera and diagnostic multi-detector CT were sequentially performed. To ensure reproducible positioning, patients were fixed in an individualised vacuum mattress with modality-specific external markers for co-registration. SPECT and CT data were initially interpreted separately and the fused images were interpreted jointly in consensus by nuclear medicine and diagnostic radiology physicians. RESULTS: SPECT was true-positive (TP) in 18 patients, true-negative (TN) in 16, false-negative (FN) in ten and false-positive (FP) in nine; CT was TP in 18 patients, TN in 21, FP in ten and FN in four. With image fusion (SPECT and CT), the scan result was TP in 27 patients (50.9%), TN in 25 patients (47.2%) and FN in one patient, this FN result being caused by multiple small liver metastases; sensitivity was 95% and specificity, 100%. The difference between SPECT and SPECT/CT was statistically as significant as the difference between CT and SPECT/CT image fusion (P<0.001). Twenty-seven abnormal SPECT findings in 17 patients could not be initially assigned to organs, but were clearly delineated after image fusion. In 21 patients (40%), clinically relevant information was obtained by image fusion as compared with SPECT alone. CONCLUSION: Co-registration of SPECT and diagnostic CT using a cost-effective immobilisation device provides excellent accuracy for tumour detection of endocrine malignancies and is superior to SPECT and CT alone. Image fusion reduces false positive results and can detect additional lesions. Anatomical information provided by CT enables precise localisation of abnormalities observed in SPECT.