During this investigation, a model of tourniquet-induced forearm ischaemia-reperfusion injury is employed to investigate the role of leucocytes in damage to the vascular endothelium during ischaemia-reperfusion injury. Leucocyte entrapment is investigated by measuring the concentration of leucocytes in venous blood leaving the arm. Neutrophil and monocyte leucocyte subpopulations are isolated by density gradient centrifugation techniques. Cell surface expression of CD11b and the intracellular production of hydrogen peroxide are measured via flow cytometry. Plasma concentrations of elastase and von Willebrand factor (vWF) are measured using enzyme-linked immunosorbemt assay (ELISA) techniques. During ischaemia-reperfusion, there was an increase in CD11b cell surface expression on neutrophils (P=0.040) and monocytes (P=0.049), and a decrease in peripheral blood leucocytes (P=0.019). There was an increase in the intracellular production of hydrogen peroxide by leucocyte subpopulations (P=0.027 [neutrophils], P=0.091 [monocytes]) and in the plasma elastase concentration (P=0.05). There was also a trend to increasing plasma concentration of vWF (P=0.0562), which was measured as a marker of endothelial damage. Ischaemia-reperfusion results in increased adhesiveness, entrapment and activation of leucocytes. Even following a mild ischaemic insult, this leucocyte response was followed immediately by evidence of endothelial damage. These results may have important implications for understanding the development of chronic diseases that involve mild ischaemic episodes.

The technique involving filtration of diluted blood enables the separate analysis of the flow properties of different cell subpopulations. This study was designed to assess the changes occurring in the flow properties and function of blood cells in stored bank blood and salvaged blood compared to patient blood in a given clinical situation. We measured hydrogen peroxide production by neutrophils and the filterability, through 5 microm Nucleopore filters, of isolated red blood cells and of diluted blood. Samples were obtained from patients undergoing aortic surgery and blood intended for transfusion: either salvaged during surgery or stored bank blood. Both salvaged and bank blood were much less filterable than patient blood, with reduced deformability of both red and white blood cells. However, salvaged blood contained highly activated neutrophils with a prolonged transit time of the 'fast-flowing' cells in the analysis compared to bank blood. Bank blood contained significantly more particles which acted as pore-blockers. Cells in bank and salvaged blood therefore have markedly abnormal flow and biochemical properties compared to patient blood.

Hypertension, decreased glucose tolerance, adverse lipid profiles and low physical activity levels are associated with increased type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) risk. High intensity interval training (HIIT), a low volume, reduced time, high intensity programme, may be a useful alternative to current government guidelines which specify a minimum of 150 minutes of physical activity per week. We describe a personalised programme of high intensity exercise which provides significant improvements in CVD risk markers. Healthy volunteers undertook 6 weeks of HIIT. T2DM and CVD risk predictors including glucose tolerance, VO2max, blood pressure (BP), and lipids were measured before and after HIIT. HIIT training was associated with beneficial changes in a range of predictors of blood flow and cardiovascular risk. There was a heterogeneous response to HIIT, with some subjects responding with favourable changes and others being non-responders to HIIT. In responders, HIIT was associated with a statistically significant (p = 0.023) increase in VO2max, from 45.4 (38.4,52.5) to 56.9 (51.2,65.7) (median (interquartile range)(ml/min/kg)). In responders HIIT resulted in a decrease in systolic BP from 127 (126,129) to 116 (106,122) (mmHg) with p = 0.026 and a decrease is diastolic blood pressure from 72 (69,74) to 57 (56,66) with p = 0.026. There was also some evidence of a beneficial change in blood lipid and glucose concentrations with HIIT. In conclusion, personalised HIIT has potential as an intervention to improve blood flow and cardiovascular health.

Increased exposure to pollution has been implicated in cardiovascular malfunction, and although studies show a relationship between PM10 and mortality, the exact biological causes are unclear. This study investigated how compromised lungs respond to instillation of nanoparticles, and the links between exposure to nanoparticles and the subsequent effects on the blood. Instillation of diesel exhaust particles and Cabosil caused significant permeability and inflammatory changes in both bleomycin-treated and control lungs, as shown by increased lung surface protein and lung:body weight ratio. This was true in edematous and maximally repairing lungs, but without significant hematological alterations. Plasma viscosity, a renowned marker for cardiovascular disease, correlated strongly statistically with free cell numbers, type I cell marker rT140, and lung acellular protein. These correlations are a new and novel insight into the mechanisms linking air pollution to cardiovascular mortality.

Our data support the hypothesis that release of elastase from activated neutrophils relates to endothelial cell damage. This may contribute to hypoxia and may result in the deterioration in clinically assessed atherosclerosis.