Abstract
BackgroundUterine blood flow is an important factor in uterine viability, but the number of blood vessels required to maintain viability is uncertain. In this study, indocyanine green (ICG) fluorescence imaging was used to examine uterine hemodynamics and vessels associated with uterine blood flow in cynomolgus macaque.MethodsThe uterus of a female cynomolgus macaque was cut from the vaginal canal to mimic a situation during trachelectomy or uterine transplantation surgery in which uterine perfusion is maintained only with uterine and ovarian vessels. Intraoperative uterine hemodynamics was observed using ICG fluorescence imaging under conditions in which various nutrient vessels were selected by clamping of blood vessels. A time-intensity curve was plotted using imaging analysis software to measure the Tmax of uterine perfusion for selected blood vessel patterns. Open surgery was performed with the uterus receiving nutritional support only from uterine vessels on one side. The size of the uterus after surgery was monitored using transabdominal ultrasonography.ResultsThe resulting time-intensity curves displayed the average intensity in the regions of the uterine corpus and uterine cervix, and in the entire uterus. Analyses of the uterine hemodynamics in the cynomolgus macaque showed that uterine vessels were significantly related to uterine perfusion (P = 0.008), whereas ovarian vessels did not have a significant relationship (P = 0.588). When uterine vessels were clamped, ovarian vessels prolonged the time needed to reach perfusion maximum. Postoperative transabdominal ultrasonography showed that the size of the uterus was not changed 2 months after surgery, with recovery of periodic menstruation. The cynomolgus macaque has got pregnant with favorable fetus well-being.ConclusionUterine vessels may be responsible for uterine blood flow, and even one uterine vessel may be sufficient to maintain uterine viability in cynomolgus macaque. Our results show that ICG fluorescence imaging is useful for evaluation of uterine blood flow since this method allows real-time observation of uterine hemodynamics.
Highlights
The uterine artery and the ovarian/vaginal arteries, which connect with branches of the uterine artery, contribute to blood supply to the uterus, and many studies on the dominant regions of the arteries have been performed [1,2,3,4]
Radical trachelectomy is performed for young women with early cervical cancer for preservation of fertility [5] and uterine blood flow is an important factor in maintenance of uterine function in this procedure
Intraoperative indocyanine green (ICG) Fluorescent Angiography ICG fluorescence imaging with a PDE enabled intraoperative real-time observation of uterine hemodynamics
Summary
The uterine artery and the ovarian/vaginal arteries, which connect with branches of the uterine artery, contribute to blood supply to the uterus, and many studies on the dominant regions of the arteries have been performed [1,2,3,4]. Uterine transplantation has been studied in mouse [18,19,20], rat [21,22,23], pig [24,25], sheep [26,27], cynomolgus macaque [28,29], and baboon [30], but pregnancy in non-human primates after transplantation has not been achieved, including after autotransplantation. This may be due to the complicated surgical techniques, ischemic reperfusion injury, and the need for ischemic preservation. Indocyanine green (ICG) fluorescence imaging was used to examine uterine hemodynamics and vessels associated with uterine blood flow in cynomolgus macaque
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