Canrenone Restores Vasorelaxation Impaired by Marinobufagenin in Human Preeclampsia.

Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Recently, we demonstrated that (i) MBG induces fibrosis in rat tissues via a mechanism involving Fli1, a negative regulator of collagen-1 synthesis, and (ii) MBG sensitive Na/K-ATPase inhibition is reversed by mineralocorticoid antagonists. We hypothesized that in human PE elevated MBG level is associated with the development of fibrosis of the umbilical arteries and that this fibrosis can be attenuated by canrenone. Fifteen patients with PE (mean BP = 118 ± 4 mmHg; 34 ± 2 years; 38 ± 0.3 weeks gest. age) and twelve gestational age-matched normal pregnant subjects (mean BP = 92 ± 2 mmHg; 34 ± 1 years; 39 ± 0.2 weeks gest. age) were enrolled in the study. PE was associated with a higher plasma MBG level, with a four-fold decrease in Fli1 level and a three-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (p < 0.01). Isolated rings of umbilical arteries from the subjects with PE exhibited impaired responses to the relaxant effect of sodium nitroprusside vs. control vessels (EC50 = 141 nmol/L vs. EC50 = 0.9 nmol/L; p < 0.001). The effects of PE on Fli1 and collagen-1 were blocked by the in vitro treatment of umbilical arteries by 10 µmol/L canrenone. Similar results were obtained for umbilical arteries pretreated with MBG. These data demonstrate that elevated MBG level is implicated in the development of the fibrosis of umbilical arteries in PE, and that this could be blocked by mineralocorticoid antagonists.

Open versus endovascular REBOA control of blood loss during cesarean delivery in the placenta accreta spectrum: A single-center retrospective case control study.

OBJECTIVE: The aim of this study was to compare two vascular control options for blood loss prevention and hysterectomy during cesarean delivery (CD2): endovascular balloon occlusion of the aorta (REBOA3) and open bilateral common iliac artery occlusion (CIAO4) in women with extensive placenta accreta spectrum (PAS5). STUDY DESIGN: This was retrospective comparison of cases of PAS using either CIAO (October 2017 through October 2018) or REBOA (November 2018 through November 2019) to prevent pathologic hemorrhage during scheduled CD. Women with confirmed placenta increta/percreta underwent either CD then intraoperative post-delivery, pre-hysterectomy open vascular control of both CIA6 (CIAO group) or pre-operative, ultrasound-guided, fluoroscopy-free REBOA followed by standard CD and balloon inflation after fetal delivery (REBOA group). Intraoperative blood loss, transfusion volumes, surgical time, blood pressure, maternal and neonatal outcomes, hospitalization length and postoperative complications were compared. RESULTS: The REBOA and CIAO groups included 12 and 16 women, respectively, with similar median age of 35 years and gestational age of 34-35 weeks. All REBOA catheters were successfully placed into aortic zone three under ultrasound guidance. The quantitated median intraoperative blood loss was significantly lower for the REBOA group, (541 [IQR 300-750] mL) compared to the CIAO group (3331 [IQR 1150-4750] mL (P = 0.001). As a result, the total volume of fluid and blood replacement therapy was significantly lower in the REBOA group (P < 0.05). Median surgical time in the REBOA group was less than half as long: 76 [IQR 64-89] minutes compared to 168 [IQR 90-222] minutes in the CIAO group (P = 0.001). None of the women with REBOA required hysterectomy, while 8/16 women in the CIAO group did (P = 0.008). Furthermore, the post-anesthesia recovery and hospital discharge times in the REBOA-group were shorter (P < 0.05). One thromboembolic complication occurred in each group. The only REBOA-associated complication was non-occlusive femoral artery thrombosis, with no surgical management required. No maternal or neonatal deaths occurred in either group. CONCLUSION: Fluoroscopy-free REBOA for women with PAS is associated with improved vascular control, perioperative blood loss, the need for transfusion and hysterectomy and reduces surgical time when compared to bilateral CIAO.