Abstract:
Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116-117 days\' gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120-123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15-75 min (TAD 1) and ∼75-135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation-\'DECIDE\' technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal D O 2 ${D_{{{\\mathrm{O}}_2}}}$ and V ̇ O 2 ${\\dot V_{{{\\mathrm{O}}_2}}}$ were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal-placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA D O 2 ${D_{{{\\mathrm{O}}_2}}}$ .
摘要:
增加胎盘灌注(PP)可以改善生长受限胎儿的结局。增加PP的一种方法可能是使用磷酸二酯酶(PDE)-5抑制剂,引起血管床的血管舒张。我们使用了临床相关磁共振成像(MRI)技术的组合来表征他达拉非输注对产妇的影响,胎盘和胎儿循环。胎龄116-117天(dGA;足月,150天),怀孕的母羊(n=6)接受了胎儿导尿手术。在120-123dGA麻醉母羊,并在三个采集窗口中进行MRI扫描:基础状态,然后在母体给药(24mg;静脉推注)后〜15-75分钟(TAD1)和〜75-135分钟(TAD2)他达拉非。相衬MRI和T2血氧饱和度用于测量血流量和氧输送。使用扩散-松弛联合成像对胎盘进行详细评估-“DECIDE”技术评估胎盘扩散和PP。在两个TAD时期,当标准化为母体左心室心输出量(LVCO)时,子宫动脉(UtA)血流量均减少。DECIDE成像发现他达拉非对胎盘扩散率或胎盘血体积分数无影响。在TAD2期,母体-胎盘血液体积分数增加。胎儿DO2${D_{{\\mathrm{O}}_2}}$和V^O2${\\dotV_{{{\\mathrm{O}}_2}}$不受母体他达拉非给药的影响。母体给药他达拉非不会增加UtA血流量,因此在UtAs水平上可能不是有效的血管扩张剂。母体-胎盘血体积分数的增加可能表明母体绒毛间隙的局部血管扩张,这可能已经补偿了UtADO2${D_{{\\mathrm{O}}_2}}}$的减少比例。