In vivo Bioimaging as a Novel Strategy to Detect Doxorubicin-Induced Damage to Gonadal Blood Vessels

INTRODUCTION: Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice. METHODS: Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio). RESULTS: Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect. CONCLUSION: We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury

Uterine rupture during pregnancy: The URIDA (uterine rupture international data acquisition) study

Objective: To describe the characteristics and peripartum outcomes of patients diagnosed with uterine rupture (UR) by an observational cohort retrospective study on 270 patients. Methods: Demographic information, surgical history, symptoms, and postoperative outcome of women and neonates after UR were collected in a large database. The statistical analysis searched for correlation between UR, previous uterine interventions, fibroids, and the successive perinatal outcomes in women with previous UR. Results: Uterine rupture was significantly associated with previous uterine surgery, occurring, on average, at 36&nbsp;weeks of pregnancy in women also without previous uterine surgery. UR did not rise exponentially with an increasing number of uterine operations. Fibroids were related to UR. The earliest UR occurred at 159&nbsp;days after hysteroscopic myomectomy, followed by laparoscopic myomectomy (251&nbsp;days) and laparotomic myomectomy (253&nbsp;days). Fertility preservation was feasible in several women. Gestational age and birth weight seemed not to be affected in the subsequent pregnancy. Conclusion: Data analysis showed that previous laparoscopic and abdominal myomectomies were associated with UR in pregnancy, and hysteroscopic myomectomy was associated at earlier gestational ages. UR did not increase exponentially with an increasing number of previous scars. UR should not be considered a contraindication to future pregnancies