Our experiments demonstrated that 4.4 µg/kg phenylephrine (equal to a single shot of 100 µg phenylephrine to a parturient of 70 kg) and 0.22 mg/kg ephedrine (equal to a single shot of 5 mg ephedrine to a parturient of 70 kg) resulted in a similar degree of increase in peripheral vascular resistance. However, the contraction effect on the uterine artery was weaker in ephedrine, particularly at 5 min and 10 min after i.v. injection. Although uterine arteries were still contracted under challenge with ephedrine after 15 min, compared with the control group, there was no statistical significance between the phenylephrine and ephedrine groups. These results suggest that compared with phenylephrine, ephedrine can provide the same degree of increase in peripheral vascular resistance while inducing a weaker uterine artery contraction effect, which makes it a better choice for treating hypotension during perioperative obstetric surgery.
Hypotension remains a frequent complication during perioperative obstetric surgery, often leading to placental hypoperfusion that endangers the life of the fetus[21-24]. Common clinical strategies for preventing and treating this hypotension include fluid therapy, posture adjustment, and the use of vasoconstrictors[5-7], in which vasoconstrictors are the most preferred therapy due to their fast action and effectiveness. The vasopressors ephedrine and phenylephrine are the two most commonly used drugs in the clinic. However, which one is the better choice for providing enough peripheral resistance vessel contraction while imposing the least effect on uterine placental perfusion remains elusive. Due to ethical reasons and limits of research methods and equipments, previous researchers prefer to study indirect indicators as vital signs of the mothers, blood gas analysis and Apgar score of the infants to reflect the effect of vasopressors on uterine placental perfusion. Therefore, the research conclusions remain controversial[22,25-28].
Doppler ultrasonography is routinely employed as a convenient and safe method for evaluating placental circulation and fetal safety during gestation period examination. Ultrasound Doppler flow imaging technology reflects blood flow through color blood flow signals, monitors the vascular resistance index, and indirectly reflects placental perfusion[29-31]. However, ultrasonography cannot accurately reflect the diameter of the uterine artery due to color expansion, and the angle of the ultrasonic probe and equipment has a great influence on measurement accuracy. Therefore, choosing a suitable measurement method to evaluate the impact of vasopressors on placental perfusion via an animal model is of great significance.
Placental perfusion depends on maternal uterine perfusion: Uterine blood flow = uterine perfusion pressure/uterine vascular resistance. In other words, in efforts to ensure uterine perfusion pressure, vascular resistance can accurately reflect uterine blood flow. According to Ohm's law, Q=ΔP/R; Q: Blood flow, R: Resistance of blood flow. Because most blood flows in a laminar manner, its resistance according to Poiseuille theorem is R=8ηl/πr4; L: Length of the blood vessel, η: Blood viscosity, R: Resistance of the vascular lumen. In most cases, the blood viscosity and vessel length do not change significantly, and the vascular diameter is changed through the relaxation and contraction of vascular smooth muscle to adjust the regulation of blood flow resistance. Therefore, the change in uterine placental flow can be directly reflected by the change in the diameter of the uterine artery.
As shown in previous studies, CT angiography is a good exam for visualizing the different branches of arteries and studying the anatomic variations in their origin, especially in the case of uterine arteries[14,32]. CT demonstrates good penetration, can clearly show certain organs and arteries, has great potential for exploring smaller branches of blood vessels, and can be used to diagnose vascular diseases such as stenosis and occlusion[33-34]. Therefore, in this study, we used CT imaging to observe changes in the diameter of the uterine and peripheral arteries to evaluate changes in placental perfusion and peripheral resistance.
Studies have shown that compared with ephedrine, phenylephrine is more likely to cause uterine artery contraction and increase vascular resistance, reduce uterine placental perfusion, and adversely affect the fetus[10,35]. In our study, both phenylephrine and ephedrine induced the same degree of peripheral vasoconstriction; however, the vasoconstriction effect on the uterine artery was different. In short, phenylephrine elicited a strong but short duration vasoconstriction effect, while ephedrine triggered a mild but long-lasting duration vasoconstriction effect, which was consistent with the aforementioned studies.
There are several limitations of our study that must be considered. First, the anatomical structure of the placenta is different in pregnant rabbits than in parturients. Accordingly, differences in the placental transfer of vasopressors may exist. In addition, human and rabbit responses to vasopressors may vary because there are species-specific differences in α- and β-adrenergic receptor distribution. Second, the drug doses used in this study are commonly used clinical single doses, and we did not carry out research using other doses of each drug. Third, the anesthesia method used for pregnant rabbits is general anesthesia, which is different from the intraspinal anesthesia used in clinical practice. The effect of intraspinal anesthesia on uterine artery diameter in pregnant rabbits needs further study. This study comprised only observation of the phenomenon and did not study the underlying mechanism.