Near-infrared spectroscopy during cardiopulmonary resuscitation for pediatric cardiac arrest: A prospective, observational study.

AIM: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge. METHODS: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020. Eligible patients had ≥30 s of rSO2 data recorded during CPR. We compared median rSO2 and percentage of rSO2 measurements above a priori thresholds for the entire event and the final five minutes of the CPR event between patients with and without ROSC and survival to discharge. RESULTS: Twenty-one patients with 23 CPR events were analyzed. ROSC was achieved in 17/23 (73.9%) events and five/21 (23.8%) patients survived to discharge. The median rSO2 was higher for events with ROSC vs. no ROSC for the overall event (62% [56%, 70%] vs. 45% [35%, 51%], p = 0.025) and for the final 5 minutes of the event (66% [55%, 72%] vs. 43% [35%, 44%], p = 0.01). Patients with ROSC had a higher percentage of measurements above 50% during the final five minutes of CPR (100% [100%, 100%] vs. 0% [0%, 29%], p = 0.01). There was no association between rSO2 and survival to discharge. CONCLUSIONS: Higher cerebral rSO2 during CPR for pediatric cardiac arrest was associated with higher rates of ROSC but not with survival to discharge.

Human cell models to study small intestinal functions: recapitulation of the crypt-villus axis.

The intestinal epithelium is continuously and rapidly renewed by a process involving cell generation, migration, and differentiation, from the stem cell population located at the bottom of the crypt to the extrusion of the terminally differentiated cells at the tip of the villus. Because of the lack of normal human intestinal cell models, most of our knowledge about the regulation of human intestinal cell functions has been derived from studies conducted on cell cultures generated from experimental animals and human colon cancers. However, important advances have been achieved over recent years in the generation of normal human intestinal cell models. These models include (a) intestinal cell lines with typical crypt cell proliferative noncommitted characteristics, (b) conditionally immortalized intestinal cell lines that can be induced to differentiate, and (c) primary cultures of differentiated villuslike cells that can be maintained in culture for up to 10 days. Each of these models should help in the investigation of the specific aspects of human intestinal function and regulation. Furthermore, taken together, these models provide an integrated system that allows an in vitro recapitulation of the entire crypt-villus axis of the normal human small intestine.

Nitric oxide and interleukin-8 as inflammatory components of cystic fibrosis.

We examined the production of reactive nitrogen intermediates in the tracheo-bronchial tree of patients with cystic fibrosis (CF). Examination of the soluble phase of sputa from 17 CF patients revealed the presence of high levels of NO2-/NO3- assayed by the Greiss reaction. We also examined the presence of the chemotactic cytokine interleukin-8 (IL-8) in these samples so as to assess another important inflammatory marker; high levels of IL-8 were present in the sputa of cystic fibrosis subjects. The elevated nitrite was not produced by the presence of Pseudomonas bacteria in the sputa, inasmuch as bacteria in culture released undetectable amounts of nitrite in culture media. Neutrophils from the sputa of CF patients with disease exacerbation released higher amounts of nitrite and IL-8. Neutrophils from the sputa were also shown to spontaneously release substantial amounts of nitrite in the supernatants, and this release was partly blocked by the antagonist NG-mono-methyl-L-arginine (L-NMMA). Blood neutrophils were shown to release nitrite only in response to challenge with CF-associated strains of Pseudomonas, and not exposure to cytokines. There was no significant differences in nitrite release between normal and CF blood polymorphonuclear leucocytes (PMNs). A study of upper airway epithelial cell lines showed that these cells released low amounts of nitrite after infection with CF-associated strains of Pseudomonas but not after cytokine exposure. Epithelial cell lines with CF or normal phenotypes were shown to release similar quantities of nitrite, upon stimulation with Pseudomonas. These data demonstrate that elevated levels of reactive nitrogen intermediates and IL-8 are produced in the tracheo-bronchial tree of subjects with CF. Levels of IL-8 and nitrite were higher in the secretions of CF subjects with disease exacerbation. The involvement of nitric oxide and other reactive nitrogen intermediates produced by neutrophils and other cells in the tissue damaging processes in CF deserves further investigation.

The involvement of nitric oxide in a mouse model of adult respiratory distress syndrome.

The release of free radicals and pro-inflammatory cytokines such as nitric oxide (NO) and tumor necrosis factor alpha (TNF alpha) is commonly observed in adult respiratory distress syndrome (ARDS) following infection or exposure to microbial products. The aim of this study was to scrutinize the involvement of NO in ARDS in a mouse model determined by the sequential exposure to lipopolysaccharide (LPS) and formyl-norleucyl-phenylalanine (FNLP). Nitrite measurements in bronchoalveolar lavage fluids (BALF) and sera demonstrated that exposure to microbial products elicits large amounts of NO in LPS/FNLP-challenged mice. This release was significantly inhibited by infusion with the inducible NO synthase antagonist, aminoguanidine (AG). Our results show that LPS/FNLP exposure induces lung damage as demonstrated by protein and lactate dehydrogenase (LDH) increases in BALF. Liver damage was also detected in LPS/FNLP-challenged mice with increases in serum ornithine-carbamoyltransferase (OCT) levels. LPS/FNLP infusion led to elevated levels of the cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) in the sera. LPS/FNLP also led to neutrophil adhesion in the lung vasculature, as seen by increased levels of myeloperoxydase. Interestingly, inhibition of NO release in challenged mice led to an important increase in markers of tissue damage in the lungs and livers, but a decrease in neutrophil recruitment. Infusion of AG in LPS/FNLP-challenged mice led to a much increased level of sera TNF alpha. These data suggest that after exposure to microbial products, NO generated as a result of activation of the inducible NO synthase blocks the full expression of tissue damage in the lungs.

Lung phagocyte bactericidal function in strains of mice resistant and susceptible to Pseudomonas aeruginosa.

The host response to Pseudomonas aeruginosa lung infection varies among inbred mouse strains. Mice of the BALB/c strain are resistant to P. aeruginosa lung infection, whereas mice of the DBA/2 strain are susceptible. This phenotypic variation correlates with a difference in the magnitude of the inflammatory response induced early following infection. In order to determine whether the ability of lung phagocytic cells to kill P. aeruginosa plays a role in the host response to the infection, we measured the in vitro bactericidal activity of resident and inflammatory alveolar and interstitial macrophages, using a temperature-sensitive mutant of P. aeruginosa. Lung macrophages obtained from resistant and susceptible animals displayed similar bactericidal activities, suggesting that the ability of phagocytes to kill P. aeruginosa does not play a crucial role in the outcome of infection. The bactericidal activity of lung phagocytes was also assessed in vivo following endobronchial infection with the temperature-sensitive mutant of P. aeruginosa. Resistant mice showed a rapid influx of polymorphonuclear leukocytes (PMNs) to the bronchoalveolar space which was shortly followed by an efficient clearance of the bacteria. Susceptible mice had a delay in both the inflammatory response to P. aeruginosa and the initiation of bacterial clearance. Susceptible mice have been shown to have a defect in tumor necrosis factor alpha production when infected intratracheally with P. aeruginosa. Intratracheal instillation of tumor necrosis factor alpha to susceptible mice at the time of infection significantly improved the recruitment of PMNs to the site of infection without affecting the process of bacterial clearance. Overall, these results suggest that both recruitment of a high number of PMNs to the lungs and an efficient activation process of the phagocytes are crucial for the prompt clearance of P. aeruginosa.

Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis.

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)