The physiology and pharmacology of oxytocin during human pregnancy

A placental enzyme, oxytocinase, rapidly degrades oxytocin (OT) in vitro. This has led to spurious results in measurement of the hormone, making it difficult to elucidate its role in pregnancy. Utilising techniques for complete oxytocinase inhibition, plasma oxytocin concentration (pOT) has been determined at induction of labour by amniotomy, during spontaneous labour and at delivery. In addition, the metabolic clearance rate (MCR) has been determined during pregnancy when oxytocinase activity is high and in the same women post-partum. In separate studies pOT has been determined (i) each minute for 30 min prior to, during and following amniotomy (n= 8) or sham amniotomy (n= 8), (ii) each minute for 15 min in the early and late first stage (< 5cm and > 5cm cervical dilation respectively; n= 8), (iii) each minute throughout the second stage (n= 8), and (iv), every 30 seconds for 15 minutes during the third stage of labour in patients managed with (n= 10) and without (n= 15) Syntometrine (5iu oxytocin & 500μg ergometrine). MCR was measured during labour and 8 weeks post-partum in the same women (n= 10) utilising 2 infusion rates (17.9 & 35.7 ng/min during pregnancy and 4.3 & 8.5 ng/min post partum). The pOT was not increased by amniotomy and remained low throughout the first and second stage of labour in most patients. During the second stage, however, an increase from 5.2 to 28 pmol/l occurred in 2 patients immediately prior to fetal delivery (taken at the mean of 4 samples at the beginning and end of the second stage respectively). All patients managed with Syntometrine demonstrated an increase in pOT following fetal delivery as did 6 of those managed without. The mean (SE) MCR of OT was significantly greater in labour than post-partum at the lower (5.7 (0.6) and 1.3 (0.1) 1/min respectively; p< 0.001) and higher (7.1 (1.9) and 1.4 (0.1) 1/min respectively; p< 0.01) OT infusion rates. In conclusion, (i) the progress of labour is not related to changes in pOT, (ii) a marked increase in pOT occurs in a minority of patients immediately prior to, or following fetal delivery, and (iii) the MCR is increased in labour at a time when oxytocinase activity is high. (DX86897)