Abstract
Preeclampsia is a complication of pregnancy characterised by gestational hypertension, proteinuria and/or end organ disease. The reduced uteroplacental perfusion (RUPP) model, via partial occlusion of the lower abdominal aorta, mimics insufficient placental perfusion as a primary causal characteristic of preeclampsia. However, a major limitation of the RUPP model is that perfusion is reduced to the entire hindquarters of the rat resulting in hindlimb ischemia. We hypothesised that clipping the uterine and ovarian arteries in the selective (s)RUPP model would provoke signs of preeclampsia while avoiding systemic ischemia. Sham, RUPP or sRUPP procedures were performed in pregnant Sprague Dawley rats on gestational day (GD)14. On GD21 uterine blood flow was significantly reduced in both the RUPP and sRUPP models while aortic flow was reduced only in RUPP. Both models resulted in increased MAP, increased vascular oxidative stress (superoxide generation), increased pro-inflammatory (RANTES) and reduced pro-angiogenic (endoglin) mediators. Vascular compliance and constriction were unaltered in either RUPP or sRUPP groups. In summary, refinements to the RUPP model simultaneously maintain the characteristic phenotype of preeclampsia and avoid peripheral ischemia; providing a useful tool which may be used to increase our knowledge and bring us closer to a solution for women affected by preeclampsia.
Highlights
IntroductionSeveral animal models have been developed which mimic signs of preeclampsia
Through the years, several animal models have been developed which mimic signs of preeclampsia
To further characterize the sRUPP model and expand on this work, we hypothesised that restriction of blood flow to the uteroplacental units – via clipping of the uterine and ovarian arteries – would induce the signs of preeclampsia in this model while avoiding potentially confounding effects caused by systemic ischemia
Summary
Several animal models have been developed which mimic signs of preeclampsia. Due to restriction of the abdominal aorta in this model, a common complication of the RUPP procedure is hindlimb ischemia which can progress to complete paraplegia and exclusion of test animals from the study (~8% of RUPP surgeries) This outcome is indicative of the fact that aortic compression, by design, occludes blood flow to the uteroplacental units and to the entire hindquarters of the animal. This raises concerns that the preeclamptic signs observed in this model, such as hypertension, are not specific to insufficient uteroplacental perfusion but may be caused by toxemia induced by systemically hypoxic tissues. To further characterize the sRUPP model and expand on this work, we hypothesised that restriction of blood flow to the uteroplacental units – via clipping of the uterine and ovarian arteries – would induce the signs of preeclampsia in this model while avoiding potentially confounding effects caused by systemic ischemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
