Using a novel in-line deoxygenating system linked to an in vitro flow-based adhesion assay and video microscopy, we have studied neutrophil recruitment and migration after hypoxia and reoxygenation of cultured human umbilical vein endothelial cells (HUVEC). Unstimulated purified neutrophils were perfused over reoxygenating HUVEC immediately after various periods of endothelial hypoxia. Adhesion to HUVEC was dependent on the duration of hypoxia, with 30, 60, and 100 min of exposure causing graded increments in neutrophil recruitment. The degree of hypoxia also markedly influenced the endothelial response. Severe hypoxia (O2 < 2.5%) induced stationary attachment and then migration of neutrophils, in contrast to rolling adhesion alone under a less intense regime (O2 = 2.5-4.0%). Judged from studies with monoclonal antibodies, P-selectin was essential for adhesion after severe hypoxia, and neutrophil immobilization was attributable to the activation of neutrophil beta 2-integrin. Perfusion of neutrophils with an antibody against interleukin-8 or a platelet-activating factor antagonist reduced levels of adhesion. However, IL-8 appeared to be the dominant agent involved in the immobilization from flow, whereas platelet-activating factor was the more potent agent involved in initiating subendothelial migration. Thus endothelial cells alone can initiate all stages of adhesion and migration of flowing neutrophils after hypoxia and reperfusion.

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As part of the Birmingham Community Aneurysm Screening Project, 3500 men aged 65-75 years from 20 urban general practices were invited for aortic ultrasonographic screening at their own general practitioner's surgery; 2669 (76.3 per cent) attended. Compliance rates varied between catchment areas, from 52.1 per cent for inner-city areas to 89.6 per cent for suburbs. Successful aortic imaging was achieved in 97.3 per cent of scans. Aortic diameter > 29 mm occurred in 219 patients (8.4 per cent) and 79 (3.0 per cent) with a diameter > 40 mm were referred for vascular surgical assessment; 140 patients with an aortic diameter of 29-40 mm are currently undergoing follow-up by serial ultrasonographic examinations at intervals of 3 months at their doctor's surgery. Risk factor analysis revealed ischaemic heart disease in 21.9 per cent of men with aneurysm, compared with 11.6 per cent in those without (P < 0.001); 18.3 per cent of men with aneurysm had had a previous myocardial infarction and 13.2 per cent had peripheral vascular disease, compared with 7.4 per cent (P < 0.001) and 8.0 per cent (P < 0.01) respectively of those without. No association was found between aneurysm and hypertension or diabetes. Community-based aortic screening is an inexpensive, effective method of diagnosis of aneurysm, with high compliance from the at-risk cohort of an urban population. Such screening programmes may help to reduce the mortality rate from aortic aneurysm rupture.

Further studies are needed to determine the effect of long-term exercise training on exercise-induced inflammation in claudication. Early work suggests, in fact, that exercise attenuates this inflammatory response. If this were confirmed then it would support the clinical impression that exercise training is beneficial in terms of symptomatic improvement and cardiovascular health in patients with intermittent claudication.

Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte-endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations.