There is evidence that tissue blood flow is regulated by retrograde transmission of signals initiated at capillary and post-capillary sites, and transmitted via the endothelium to modulate pre-capillary resistance. We have used pre-eclampsia as a model to test the hypothesis that normal endothelium is required to enable adjustment of blood flow to match tissue requirements. Integrity of the endothelial pathway was assessed by measuring calf blood flow at increasing venous pressures, using an established small cumulative-step venous-congestion plethysmography protocol in ten women with pre-eclampsia, 17 normal pregnant controls and ten non-pregnant women. Endothelial cell activation was assessed by measuring plasma levels of the cell adhesion molecules, intercellular cell-adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1) and E-selectin. Baseline calf blood flow was significantly lower in pre-eclampsia than in the other two groups ( P <0.0001; ANOVA). In the pre-eclampsia group, there was a fall in blood flow as venous congestion pressure was raised ( P <0.0001; ANOVA). No such change was observed in the other two groups. A significant inverse correlation was observed between the reduction in blood flow in pre-eclampsia and the levels of E-selectin ( r =-0.92, P =0.0002), VCAM-1 ( r =-0.93, P =0.0008) and ICAM-1 ( r =-0.86, P =0.001). The differences between the pre-eclamptic women and the other two groups support the notion that the failure to sustain blood flow during a cumulative pressure step protocol in the pre-eclamptic group might be influenced by interference with the retrograde transmission of signals via the endothelium in these patients.
The clinical presentation of pre-eclampsia suggests that microvascular dysfunction may play a role in the maternal manifestations of the disease. Isovolumetric venous pressure ( P V i ) 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 P V i . A small cumulative step strain-gauge plethysmography protocol was used to compare P V i 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. P V i was significantly greater in the pre-eclampsia group, relative to the normal pregnant and non-pregnant controls ( P <0.001, ANOVA, for both comparisons). P V i 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 P V i 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 P V i 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.
Multiple organ dysfunction followed by end organ failure occurs in pre-eclampsia. While one would intuitively reason that one of the factors contributing to the end organ failure is poor nutritional blood flow, this has yet to be demonstrated. The aim of the present study was to determine whether changes in resting nutritional blood flow occur in pre-eclampsia. We used strain-gauge plethysmography to study calf blood flow in 19 women with pre-eclampsia, 13 normal pregnant women and 17 non-pregnant controls. We reasoned that, since the calf comprises mostly skeletal muscle, without anastomotic channels, blood flowing through this region would primarily reflect nutritive flow. Calf blood flow was significantly reduced in women with pre-eclampsia (1.95±0.9 ml·min -1 ·100 ml -1 ) compared with normal pregnant (3.9±1.4 ml·min -1 ·100 ml -1 ) and non-pregnant (3.8±1.0 ml·min -1 ·100 ml -1 ) women ( P = 0.0004 and P = 0.0005 respectively; ANOVA). Blood flow in pre-eclampsia was also correlated significantly with platelet count as an index of disease severity. In addition, there was a significant negative correlation between blood flow and systolic blood pressure ( r = -0.69, P = 0.004) in the women with pre-eclampsia. These findings support the hypothesis that nutritional blood flow is reduced in pre-eclampsia. We suggest that measurement of resting calf blood flow could give a non-invasive index of deterioration of nutritive blood flow to vital organs in pre-eclampsia.