Plasma CD59 concentrations are increased in preeclampsia with severe features and correlate with laboratory measures of end-organ injury.

OBJECTIVES: Dysregulation of CD59 may lead to increased complement-mediated end-organ injury in preeclampsia. We sought to determine if soluble CD59 concentrations are altered in preeclampsia with severe features. STUDY DESIGN: Observational case-control study, which enrolled subjects prospectively from six centers in Colombia from 2015 to 2016. Cases had preeclampsia with severe features and controls were either healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. Trained coordinators collected clinical data, blood and urine. Analyses were by test of medians and Spearman's correlation. MAIN OUTCOME MEASURES: Soluble CD59 concentration in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 352 subjects were enrolled (104 cases; 248 controls). Compared to healthy women or those with other hypertensive disorders of pregnancy, women with preeclampsia with severe features had increased concentration of CD59 in plasma (P < 0.001) and decreased CD59 in urine (P = 0.01). In sub-group analyses, plasma CD59 concentrations were increased in preeclampsia with severe features compared to healthy controls (P < 0.001) or controls with either chronic hypertension (P = 0.002) or gestational hypertension (P = 0.02). Increased plasma CD59 concentrations correlated with decreased platelet count and increased lactate dehydrogenase, creatinine, aspartate transaminase, urine protein/creatinine ratio, systolic blood pressure and diastolic blood pressure (P < 0.01, all correlations). CONCLUSION: In women with preeclampsia with severe features, soluble CD59 concentrations were increased in plasma and decreased in urine, and plasma levels correlated with increased blood pressure and end-organ injury. Soluble CD59 concentrations may help identify a subset of women with preeclampsia that have altered regulation of terminal complement proteins.

Fetal sheep left ventricle is more sensitive than right ventricle to progressively worsening hypoxemia and acidemia.

OBJECTIVE: In a sheep model we tested the hypothesis that the fetal left ventricle is less tolerant to worsening acidemia than the right ventricle. STUDY DESIGN: At 106-124/145 days of gestation, 12 fetuses were instrumented. After a 4-day recovery, placental vascular resistance was increased by fetal angiotensin (AT) II infusion. After a 2h ATII infusion, to further deteriorate fetal oxygenation, maternal hypoxemia was induced. Fetal cardiac function and hemodynamics were assessed by tissue Doppler imaging (TDI) and pulsed Doppler imaging. Ultrasonography was performed at baseline, at 1 and 2h after the beginning of ATII infusion and during the ATII+hypoxemia phase. RESULTS: Fetal pH and pO2 decreased significantly and progressively during the experiment. Left ventricular TDI-derived isovolumic relaxation velocity (IVRV) was lower during ATII 2h and ATII+hypoxemia phases than at baseline. The IVRV deceleration was significantly less during the ATII+hypoxemia phase than at baseline. Right ventricular IVRV was significantly lower during the ATII+hypoxemia phase than at baseline. IVRV deceleration did not change. Only left ventricular IVRV deceleration correlated with fetal pO2 (R=0.36, p<0.05). Fetal right and left ventricular cardiac outputs, as well as umbilical artery, aortic isthmus and ductus venosus pulsatility indices remained unchanged during the experiment. CONCLUSION: Our results show that signs of cardiac dysfunction develop earlier in the left ventricle than in the right ventricle. The fetal left ventricle seems to be more sensitive to progressively worsening hypoxemia and acidemia than the right ventricle.