Do lower cuff pressures reduce damage to the tracheal mucosa? A scanning electron microscopy study in neonatal pigs.

BACKGROUND: Modern high volume-low pressure (HVLP) endotracheal tubes (ETT) cuffs can seal the trachea using baseline cuff pressures (CP) lower than peak inspiratory airway pressures (PIP). The aim of the study was to determine whether this technique reduces the damage to the tracheal mucosa compared to constant CP of 20 cmH(2)O. METHODS: Eighteen piglets were intubated with an ID 4.0 mm HVLP cuffed ETT (Microcuff PET) and artificially ventilated with 20 cmH(2)O PIP and 5 cmH(2)O PEEP. Animals were randomly allocated to two groups of CP: group A (just seal; n = 9) and group B (20 cmH(2)O; n = 9), controlled constantly with a manometer during the following 4-h study period under sevoflurane anesthesia. After euthanasia, cuff position was marked in situ. Damage in the cuff region was evaluated with scanning electron microscopy (SEM) examination by grading of mucosal damage and by estimating percentage of intact mucosal area both by a blinded observer. RESULTS: Maximal CP to seal the trachea in group A ranged from 12 to 18 cmH(2)O (median: 14 cmH(2)O). Using a mixed effects model approach, the estimated mean effect of group B vs group A was an increase of 17.9% (SE 8.1%) higher proportion of pictures with an area of at least 5% intact mucosa (P = 0.042). CONCLUSION: Minimal sealing pressures with cyclic pressure changes from CP did not result in decreased damage to the tracheal mucosa compared to constant CP of 20 cmH(2)O in this short-term animal trial.

Critical role for lipid raft-associated Src kinases in activation of PI3K-Akt signalling.

Lipid rafts are membrane microdomains distinct from caveolae, whose functions in polypeptide growth factor signalling remain unclear. Here we show that in small cell lung cancer (SCLC) cells, specific growth factor receptors such as c-Kit associate with lipid rafts and that these domains play a critical role in the activation of phosphoinositide 3-kinase (PI3K) signalling. The class IA p85/p110alpha associated with Src in lipid rafts and was activated by Src in vitro. Lipid raft integrity was essential for Src activation in response to stem cell factor (SCF) and raft disruption selectively inhibited activation of protein kinase B (PKB)/Akt in response to SCF stimulation. Moreover, inhibition of Src kinases blocked PKB/Akt activation and SCLC cell growth. The use of fibroblasts with targeted deletion of the Src family kinase genes confirmed the role of Src kinases in PKB/Akt activation by growth factor receptors. Moreover a constitutively activated mutant of Src also stimulated PI3K/Akt in lipid rafts, indicating that these microdomains play a role in oncogenic signalling. Together our data demonstrate that lipid rafts play a key role in the activation of PI3K signalling by facilitating the interaction of Src with specific PI3K isoforms.