Modulation of monocyte chemoattractant protein-1 expression by ischaemic preconditioning in a lung autotransplant model

Objectives: Monocyte chemoattractant protein-1 (MCP-1) is believed to play a crucial role in lung ischaemia-reperfusion injury (LIRI). Ischaemic preconditioning (IP) has been shown to protect several organs from ischaemia-reperfusion (IR) injury, although less is known about IP's effect on MCP-1 modulation. The objective of this study was to investigate IP's effect on MCP-1 expression in lung tissue and its relationship with oxidative stress and proinflammatory cytokine production in an experimental LIRI model. Methods: Two groups (IP and control groups) of seven large white pigs underwent a lung autotransplant (left pneumonectomy, ex situ superior lobectomy and lower lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two cycles of 5 min of left pulmonary artery occlusion with a 5 min interval of reperfusion between the two occlusions. Blood samples and lung biopsies were obtained at prepneumonectomy (PPn), at prereperfusion (PRp) and up to 30 min after reperfusion of the implanted lobe (Rp-10' and Rp-30'). Haemodynamic and blood-gas measurements, evaluation of oxidative stress in lung tissue and MCP-1, tumour necrosis factor-α (TNF-α) and IL-1 protein and mRNA measurements in lung tissue were performed. Nonparametric tests were used to compare differences between groups. Data are expressed as mean ± SEM. Results: In control lungs, MCP-1 protein levels were found to be higher at PRp, Rp-10' and Rp-30' than at PPn (0.59 ± 0.1 vs. 0.21 ± 0.05, 0.47 ± 0.01 vs. 0.21 ± 0.05 and 0.56 ± 0.01 vs. 0.21 ± 0.05, respectively; P < 0.05). These differences were not evident in the IP group. MCP-1 levels at PRp, Rp-10' and Rp-30' were significantly higher in the control group than in the IP group (0.59 ± 0.1 vs. 0.15 ± 0.02, 0.47 ± 0.01 vs. 0.13 ± 0.01 and 0.56 ± 0.01 vs. 0.27 ± 0.01, respectively; P < 0.05). MCP-1, TNF-α and IL-1 mRNA expressions were lower at PRp, Rp-10' and Rp-30' (control vs. IP group, P < 0.05) when IP was carried out. Lipid peroxidation metabolites and myeloperoxidase activity increase in lung tissue were prevented by IP. Conclusions: In this model, LIRI induced the expression of MCP-1 and the proinflammatory proteins TNF-α and IL-1 in control lungs. IP significantly reduced the expression of these chemokines and cytokines. These features may explain the reduction of oxidative stress observed with IP.Instituto Salud Carlos IIISociedad Española de Neuomologia y Cirugía ToracicaDepto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpu

The effects of anesthetic preconditioning with sevoflurane in an experimental lung autotransplant model in pigs

Background: Ischemia-reperfusion lung injury is doubly important in thoracic surgery because of the associated ventilation damage to 1 lung. In this study we evaluated the cytoprotective effects of sevoflurane in a pulmonary autotransplant model in pigs. Methods: Twenty Large White pigs undergoing pneumonectomy plus lung autotransplant were divided into 2 10-member groups on the basis of the anesthetic received (propofol or sevoflurane). Proinflammatory mediators, oxidative stress, nitric oxide metabolism, and hemodynamic and blood variables were measured at 5 different time points. Results: There was an increase of oxidative stress markers and proinflammatory mediators in the propofol group, whereas the hemodynamic variables were similar in both groups. Conclusions: We demonstrated that sevoflurane decreased the inflammatory response and oxidative stress in a live ischemia-reperfusion lung model.Instituto de Salud Carlos IIILABORATORIOS ABBOTSOCIEDAD ESPAÑOLA NEUMOLOGÍA Y CIRUGÍA TORÁCICADepto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpu