G.J. Scheffer

α7 Nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced tumour necrosis factor-α production and lung injury

BACKGROUNDnMechanical ventilation (MV) induces an inflammatory response that can lead to lung injury. The vagus nerve can limit the inflammatory response through the cholinergic anti-inflammatory pathway. We evaluated the effects of stimulation of the cholinergic anti-inflammatory pathway with the selective partial α7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 on inflammation and lung injury induced by MV using clinically relevant ventilator settings. Furthermore, we investigated whether altering endogenous cholinergic signalling, by administration of the non-specific nAChR antagonist mecamylamine and the peripherally acting acetylcholinesterase inhibitor neostigmine, modulates the MV-induced inflammatory response.nnnMETHODSnC57BL6 mice were injected i.p. with either the selective α7nAChR agonist GTS-21 (8 mg kg(-1)), the acetylcholinesterase inhibitor neostigmine (80 μg kg(-1)), the nAChR antagonist mecamylamine (1 mg kg(-1)), or a placebo; followed by 4 h of MV (8 ml kg(-1), 1.5 cm H(2)O PEEP).nnnRESULTSnMV resulted in release of cytokines in plasma and lungs compared with unventilated mice. Lung and plasma levels of tumour necrosis factor (TNF)-α, but not of interleukin-10, were lower in GTS-21-treated animals compared with placebo (P<0.05). In addition, GTS-21 lowered the alveolar-arterial gradient, indicating improved lung function (P=0.04). Neither neostigmine nor mecamylamine had an effect on MV-induced inflammation or lung function.nnnCONCLUSIONSnMV with clinically relevant ventilator settings results in pulmonary and systemic inflammation. Stimulation of the cholinergic anti-inflammatory pathway with GTS-21 attenuates MV-induced release of TNF-α, which was associated with reduced lung injury. Modulation of endogenous cholinergic signalling did not affect the MV-induced inflammatory response. Selective stimulation of the cholinergic anti-inflammatory pathway may represent new treatment options for MV-induced lung injury.

Continuous non-invasive finger arterial pressure monitoring reflects intra-arterial pressure changes in children undergoing cardiac surgery

BACKGROUNDnContinuous non-invasive measurement of finger arterial pressure (FAP) is a reliable technology in adults. FAP is measured with an inflatable cuff around the finger and simultaneously converted to a reconstructed brachial artery pressure waveform (reBAP) by the Nexfin™ device. We assessed the adequacy of a prototype device (Nexfin-paediatric), designed for a paediatric population, for detecting rapid arterial pressure changes in children during cardiac surgery.nnnMETHODSnThirteen anaesthetized children with a median age of 11 months (2 months-7 yr) undergoing congenital cardiac surgery were included in the study. reBAP and intra-arterial pressure (IAP) were recorded simultaneously during the surgical procedure. To assess the accuracy of reBAP in tracking arterial pressure changes, the four largest IAP variations within a 5 min time interval were identified from each procedure. These variations were compared offline with reBAP during a 10 s control period before and a 10 s period after an arterial pressure change had occurred.nnnRESULTSnIn 10 out of 13 children, a non-invasive arterial pressure recording could be obtained. Therefore, recordings from these 10 children were eligible for further analysis, resulting in 40 data points. The correlation coefficient between reBAP and IAP in tracking mean arterial pressure (MAP) changes was 0.98. reBAP followed changes in IAP with a mean bias for systolic, diastolic arterial pressure, and MAP of 0.0 mm Hg (sd 5.8), 0.1 (sd 2.8), and 0.19 (sd 2.7), respectively.nnnCONCLUSIONSnThe prototype device closely follows arterial pressure changes in children. However, in a considerable number of attempts, obtaining a signal was time-consuming or unsuccessful. This technique seems promising but requires further technical development.

Effects of Vagus Nerve Stimulation and Vagotomy on Systemic and Pulmonary Inflammation in a Two-Hit Model in Rats

Pulmonary inflammation contributes to ventilator-induced lung injury. Sepsis-induced pulmonary inflammation (first hit) may be potentiated by mechanical ventilation (MV, second hit). Electrical stimulation of the vagus nerve has been shown to attenuate inflammation in various animal models through the cholinergic anti-inflammatory pathway. We determined the effects of vagotomy (VGX) and vagus nerve stimulation (VNS) on systemic and pulmonary inflammation in a two-hit model. Male Sprague-Dawley rats were i.v. administered lipopolysaccharide (LPS) and subsequently underwent VGX, VNS or a sham operation. 1 hour following LPS, MV with low (8 mL/kg) or moderate (15 mL/kg) tidal volumes was initiated, or animals were left breathing spontaneously (SP). After 4 hours of MV or SP, rats were sacrificed. Cytokine and blood gas analysis was performed. MV with 15, but not 8 mL/kg, potentiated the LPS-induced pulmonary pro-inflammatory cytokine response (TNF-α, IL-6, KC: p<0.05 compared to LPS-SP), but did not affect systemic inflammation or impair oxygenation. VGX enhanced the LPS-induced pulmonary, but not systemic pro-inflammatory cytokine response in spontaneously breathing, but not in MV animals (TNF-α, IL-6, KC: p<0.05 compared to SHAM), and resulted in decreased pO2 (p<0.05 compared to sham-operated animals). VNS did not affect any of the studied parameters in both SP and MV animals. In conclusion, MV with moderate tidal volumes potentiates the pulmonary inflammatory response elicited by systemic LPS administration. No beneficial effects of vagus nerve stimulation performed following LPS administration were found. These results questions the clinical applicability of stimulation of the cholinergic anti-inflammatory pathway in systemically inflamed patients admitted to the ICU where MV is initiated.

Isoflurane attenuates pulmonary interleukin‐1β and systemic tumor necrosis factor‐α following mechanical ventilation in healthy mice

Background: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro‐inflammatory state is a risk factor for ventilator‐induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV‐induced inflammatory response in healthy lungs is reduced by isoflurane.

The relation between skin temperature increase and sensory block height in spinal anaesthesia using infrared thermography

Background and objectives: To evaluate the feasibility of determining the extent of sympathetic blockade by skin temperature measurement with infrared thermography and relate the cranial extent of the temperature increase to that of the sensory block after spinal anaesthesia.

Mechanical ventilation of mice under general anesthesia during experimental procedures

Mechanical ventilation is frequently used in patients under general anesthesia during invasive procedures. Invasive animal experiments similarly require the maintenance of normal hemodynamic and pulmonary parameters during long-term general anesthesia. The authors describe a method for mechanical ventilation of mice. Mice were ventilated and monitored for up to 8 h of general anesthesia during surgery. Hemodynamic and pulmonary parameters remained within the normal ranges. The authors believe that this ventilation technique can be of great value for experimental procedures in mice that require general anesthesia.