Gianni D Angelini

Interactions of cardiopulmonary bypass and erythrocyte transfusion in the pathogenesis of pulmonary dysfunction in Swine.

Background:Allogeneic erythrocyte transfusion in cardiac surgical patients is associated with a fourfold increase in pulmonary complications. Our understanding of the processes underlying these observations is poor and there is no experimental model of transfusion-related acute lung injury that shows homology to cardiac surgical patients. Our objective was to develop a novel swine recovery model to determine how two clinical risk factors, allogenic erythrocyte transfusion and cardiopulmonary bypass, interact in the genesis of postcardiac surgery acute lung injury. Methods:Thirty-six pigs were infused with allogeneic 14- or 42-day-old erythrocytes or they underwent cardiopulmonary bypass with or without transfusion of 42-day erythrocyte. Controls received saline. All pigs were recovered and assessed for pulmonary dysfunction, inflammation, and endothelial activation at 24 h. Results:Transfusion of stored allogeneic erythrocytes in pigs compared with sham caused pulmonary dysfunction characterized by reduced lung compliance (mean difference −3.36 [95% CI, −5.31 to −1.42] ml/cm H2O), an increase in protein levels in bronchoalveolar lavage fluid, histological lung injury inflammation, and endothelial activation. Transfusion of blood stored for up to 42 days resulted in greater protein levels in bronchoalveolar lavage fluid, macrophage infiltration, platelet activation, and depletion of T-lymphocytes in recipient lungs versus 14-day-old blood. Transfusion interacted with cardiopulmonary bypass to increase lung injury in the absence of platelet activation. Conclusions:In this novel large animal model of allogeneic erythrocyte transfusion, pulmonary dysfunction occurs in the absence of any priming event, is increased when combined with other inflammatory stimuli, and is mediated by monocyte activation and T-lymphocyte depletion.

Consumption of Broccoli Sprouts AttenuatesIntracellular P38 Map Kinase and ReactiveOxygen Species Pro-Inflammatory Activationin Human Leukocytes: A Randomised-Controlled Trial

Dietary consumption of green vegetables has a protective association with reduction in cardiovascular diseases. The thiocyanate compound sulforaphane, which is obtained from green vegetables, induces antioxidant genes and can protect against pro-inflammatory cellular activation. Our objective was to investigate the influence of sulforaphane on leukocyte pro-inflammatory activation and assess the impact of a sulforaphane-rich diet on leukocyte activation in vivo. Healthy human volunteers were randomised to consume either broccoli sprout homogenates (BSH) rich in sulforaphane or alfalfa sprout homogenates (ASH) as controls in a double-blind crossover trial. Blood was sampled prior to and then at 1 h, 6 h and 24 h post-homogenate consumption and analysed by flow cytometry for intracellular markers of leukocyte activation, reactive oxygen species (ROS), p38 mitogen activated protein (MAP) kinase phosphorylation and p65 nuclear factor kappa B (NF-κB) phosphorylation. Plasma levels of sulforaphane were determined by LC-MS methods. Six participants were recruited into the study. Plasma concentrations of sulforaphane were 30 ng/ml at one hour following BSH and undetectable following ASH consumption. In the control ASH group, ROS activation and p38 MAP kinase phosphorylation were enhanced one hour following consumption. This increase was attenuated in the BSH group (ROS, p<0.02: p38, p<0.001 comparison between groups). We conclude that ingestion of sulforaphane-rich homogenate can protect against pro-inflammatory activation in circulating leukocytes by attenuation of constitutive ROS and p38 MAP kinase.