The use of pentaerythrityltetranitrate (PETN), a nitric oxide donor, to improve utero- and fetal-placental perfusion pregnancies with established pathological flow pattern in the Aa. uterinae beyond 20 weeks of gestation

Author(s):  
E Schleußner ◽  
S Bowkalow ◽  
U Schneider ◽  
C Kähler ◽  
T Groten
2014 ◽  
Vol 42 (4) ◽  
Author(s):  
Ekkehard Schleussner ◽  
Thomas Lehmann ◽  
Christiane Kähler ◽  
Uwe Schneider ◽  
Dietmar Schlembach ◽  
...  

AbstractIntrauterine growth restriction (IUGR) and preeclampsia (PE) are associated with impaired placentation. Patients who are at risk of developing both these disorders can be identified by abnormal uterine artery Doppler at mid-trimester pregnancy. Nitric oxide (NO)-donors like pentaerithrityl-tetranitrate (PETN) reduce the impedance in the uteroplacental vessels and possess protecting effects on the endothelium. We tested the effectiveness of the NO-donor PETN for secondary prevention of IUGR, PE, and preterm birth in pregnancies at risk. Some 111 women who presented with abnormal placental perfusion at 19–24 weeks of gestation (w.o.g.) were included into a prospective, randomized, placebo-controlled, double-blinded study. The primary endpoint was IUGR and/or perinatal death. Secondary endpoints were preterm birth, PE, and placental abruption. Pentaerithrityl-tetranitrate significantly decreased the risk for IUGR and/or perinatal death [adjusted relative risk (RR) 0.410; 95% confidence interval, CI, 0.184–0.914] and for IUGR (adjusted RR 0.436; 95% CI 0.196–0.970). Preterm birth before 32 w.o.g. (adjusted RR 0.204; 95% CI 0.052–0.801) was reduced, but not the risk for PE. No placental abruption occurred in the PETN, but five occurred in the placebo group. These results suggest that secondary prophylaxis of adverse pregnancy outcome might be feasible in pregnancies exhibiting abnormal placentation using PETN.


Circulation ◽  
1997 ◽  
Vol 95 (9) ◽  
pp. 2303-2311 ◽  
Author(s):  
Nobuhiko Ito ◽  
Josef Bartunek ◽  
Kenneth W. Spitzer ◽  
Beverly H. Lorell

2019 ◽  
Vol 75 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Odel Soren ◽  
Ardeshir Rineh ◽  
Diogo G Silva ◽  
Yuming Cai ◽  
Robert P Howlin ◽  
...  

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.


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