Evidence of impaired microvascular function in pre-eclampsia: a non-invasive study.
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.
Anim-Nyame
N
N
Department of Maternal and Fetal Medicine, Imperial College School of Medicine at Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, U.K. n.anim@ic.ac.uk
Gamble
J
J
Sooranna
S R
SR
Johnson
M R
MR
Sullivan
M H
MH
Steer
P J
PJ
D000328:Adult; D016022:Case-Control Studies; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006400:Hematocrit; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D019272:Leukocyte Elastase / Q000097:blood; D008833:Microcirculation; D018375:Neutrophil Activation; D021041:Placental Circulation; D010991:Plethysmography; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D011247:Pregnancy; D012044:Regression Analysis; D014527:Uric Acid / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014690:Venous Pressure
D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014527:Uric Acid; D019272:Leukocyte Elastase