Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>The development of bronchial hyperreactivity (BHR) subsequent to precapillary pulmonary hypertension (PHT) was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP) and prostacyclin) involved in the control of the pulmonary vascular and bronchial tones.</p> <p>Methods</p> <p>Five groups of rats underwent surgery to prepare an aorta-caval shunt (ACS) to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group (ACS controls), while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine (2, 4, 8 12 and 24 μg/kg/min) was determined by using the forced oscillation technique to assess the airway resistance (Raw).</p> <p>Results</p> <p>BHR developed in the untreated rats, as reflected by a significant decrease in ED₅₀, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure (Ppa; 28%, p = 0.035) and BHR (ED₅₀= 9.9 ± 1.7 vs. 43 ± 11 μg/kg in ACS control and iloprost-treated rats, respectively, p = 0.008). Significant correlations were found between the levels of Ppa and ED₅₀(R = -0.59, p = 0.016), indicating that mechanical interdependence is primarily responsible for the development of BHR.</p> <p>Conclusions</p> <p>The efficiency of such treatment demonstrates that re-establishment of the balance of constrictor/dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.</p

Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS)trial

Background: In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. Methods: In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks