Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to ischemic stress. Ho-1-deficient (Hmox1-/-) mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled CO. CO drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of the gene encoding plasminogen activator inhibitor-1 (PAI-1) in mononuclear phagocytes, which reduced accrual of microvascular fibrin. CO-mediated ischemic protection observed in wild-type mice was lost in mice null for the gene encoding PAI-1 (Serpine1). These data establish a fundamental link between CO and prevention of ischemic injury based on the ability of CO to derepress the fibrinolytic axis. These data also point to a potential therapeutic use for inhaled CO.

This review provides the theoretical background of phenotypic and gene-based changes in the vessel wall triggered by acute hypoxia. Only in the last few decades has the endothelium been ascribed a prominent role as a modulator of vascular homeostasis under both physiological and pathological conditions. Molecular mechanisms leading to endothelial activation are being rapidly elucidated and their contribution to vascular dysfunction during hypoxia becoming better understood. New insights gained from hypoxic cell culture and ischaemic organ models may ultimately lead to new treatment strategies. If nothing else, insights gained from vascular research will lead to a more complete understanding of the inflammatory processes in blood vessels and how they impact on human disease.

Leukodepletion should be considered in critically ill infants with B pertussis and leukocytosis.

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The UK neonatal ECMO service achieves good outcomes and with overall survival rate reaching 80% compares favourably with international results. Advanced respiratory therapies are used widely in UK ECMO patients. Identification of higher OI and older age at ECMO as risk factors in non-CDH neonates reinforces the importance of timely referral for ECMO.