European Journal of Clinical Investigation (2006) 36, 133–140 © 2006 Blackwell Publishing Ltd Blackwell Publishing Ltd Hypoxic inhibition of human myometrial contractions in vitro: implications for the regulation of parturition G. J. Bugg, M. J. Riley, T. A. Johnston, P. N. Baker and M. J. Taggart St Mary’s Hospital, University of Manchester, Manchester, UK Abstract Background Insufficient tissue oxygenation is a likely contribution to weak, inco-ordinate human uterine contractile activity characteristic of prolonged, dysfunctional labour. However, the direct effects of hypoxia on human myometrial contractility has, surprisingly, not yet been detailed. Therefore, we report the influence of hypoxia on spontaneous and agonist-induced carbachol, prostaglandin (PGF2α), and oxytocin contractions of myometria from nonpregnant and pregnant women. Materials and methods Uterine biopsies were obtained from pregnant women at term undergoing elective Caesarean section and nonpregnant women undergoing hysterectomy. Myometrial strips were equilibrated at 37 °C in normoxic physiological salt solution (95% air/5% CO 2 ) and the influence of hypoxia (95% N 2 /5% CO 2 ) on contractility was investigated. Results Hypoxia resulted in a significant reduction in spontaneous contractile function; nonpregnant tissue was less resistant to the deleterious effects of hypoxia. Agonist-induced contractions, while being more resistant to hypoxia than spontaneous contractions, were also significantly inhibited. In myometria of pregnant women the PGF2α- or oxytocin-induced contractility was more resistant to hypoxia than carbachol. Finally, the inhibitory actions of hypoxia were exacerbated with repeated oxytocin administration with a more severe effect on contractile integral than on initial phasic contraction amplitude. Conclusions We detail, for the first time, the effects of hypoxia on contractility of human myometria from nonpregnant and pregnant women. Physiologically important uterotonic agents are more resistant to the effects of hypoxia than spontaneous contractions although repeated stimulation with oxytocin during hypoxia results in progressively less force. The results indicate that if significant hypoxia occurs in vivo then it is a likely contributory factor to the pathways underlying prolonged dysfunctional labour. Keywords Dysfunctional labour, human myometrium, hypoxia. Eur J Clin Invest 2006; 36 (2): 133–140 Introduction During pregnancy the smooth muscle of the uterus (the myometrium) undergoes extensive changes designed to attain the requisite uterine contractile ability for safe child- birth. Such myometrial contractile effort during parturition can only be maintained if the circulatory supply of oxygen and nutrients to the uterus is sufficient to meet metabolic demands. However, in the last 40 years, a number of in vivo studies, each employing different experimental techniques, have suggested that there is an inverse relationship between uterine contractions at term and blood flow through the organ [1–4]. The strength of uterine contractions may indeed be powerful enough to occlude localized blood sup- ply as well as influence levels of fetal cerebral oxygenation. These findings are complimented by analogous in vivo studies in the rat, whereby partial occlusion of the uterine artery, to invoke a situation of reduced perfusion of nutrients and oxygen to the uterine organ, resulted in diminished spon- taneous uterine contractions [5,6]. The inescapable conclusion from the above data is that uterine blood flow during parturition is highly dynamic and that such fluctuations are highly likely to give rise to episodes Maternal & Fetal Health Research Centre, St Mary’s Hospital, University of Manchester, Manchester, UK (G. J. Bugg, M. J. Riley, T. A. Johnston, P. N. Baker, M. J. Taggart). Correspondence to: Dr George J Bugg, C Floor, East Block, Queens Medical Centre, Nottingham, NG7 2UH, UK. Tel.: +44 (0)115 9249924; e-mail: george.bugg@qmc.nhs.uk Received 16 June 2005; accepted 11 December 2005