Evidence of impaired microvascular function in pre-eclampsia: a non-invasive study

Abstract

The clinical presentation of pre-eclampsia suggests that microvascular dysfunction may play a role in the maternal manifestations of the disease. Isovolumetric venous pressure (PVi) is an index of microvascular function, reflecting local plasma colloid osmotic (oncotic) pressure, and is abnormal in clinical conditions with microvascular dysfunction. We hypothesized that, in pre-eclampsia, post-capillary margination of neutrophils would increase post-capillary resistance, and therefore PVi. A small cumulative step strain-gauge plethysmography protocol was used to compare PVi in 18 women with pre-eclampsia, 16 normal pregnant women and 17 non-pregnant controls. Circulating levels of vascular cell-adhesion molecule-1 (VCAM-1), intercellular cell-adhesion molecule-1 (ICAM-1) and E-selectin, and neutrophil elastase, were measured to assess endothelial and neutrophil activation respectively. PVi was significantly greater in the pre-eclampsia group, relative to the normal pregnant and non-pregnant controls (P<0.001, ANOVA, for both comparisons). PVi was significantly lower during normal pregnancy compared with the non-pregnant controls (P = 0.001). Plasma levels of neutrophil elastase, VCAM-1, ICAM-1 and E-selectin (P = 0.001) were significantly greater in the pre-eclamptics than the controls. Significant positive correlations were observed between PVi and neutrophil elastase (r = 0.71, P = 0.001), VCAM-1 (r = 0.52, P = 0.03), ICAM-1 (r = 0.67, P = 0.002), E-selectin (r = 0.69, P = 0.001), uric acid levels (r = 0.54, P = 0.02) and haematocrit (r = 0.64, P = 0.004) in pre-eclampsia. The relationship with the platelet count was negative (r =-0.65, P = 0.003). No significant correlations were observed between PVi and maternal age, gestational age, total protein, albumin, diastolic blood pressures, age, body mass index and infant birth mass in the normal pregnant and non-pregnant controls. These data suggest that microvascular dysfunction occurs in pre-eclampsia, and that it is related to alterations in endothelial cell and neutrophil activation.