Uterine dystocia is characterised by weak, unco-ordinated contractions and a prolongation of labour; it is the commonest cause of Caesarean sections (CS). As hypoxia may be one of the causes of dystocia, we investigate in this study the effects of metabolic inhibition on contractions of human myometrium, with and without agonists.
Human myometrial biopsies were obtained with informed consent and ethical committee approval, from non-labouring women at term undergoing elective CS. Longitudinal muscle strips were dissected, loaded with indo-1 for Ca2+ measurement and attached to a pressure transducer. Tissues were superfused with physiological saline, pH 7.4 at 35 °C, and cyanide (2 mM) applied.
Spontaneous contractions of the myometrium, and their associated intracellular Ca2+ transients were rapidly (5 min) abolished by cyanide (n = 7); basal Ca2+, however, was elevated. A significant (P < 0.05, paired t test) reduction in force production also occurred when agonists were used to stimulate the myometrium (oxytocin, 100 nM, n = 9, or carbachol, 100 mM, n = 7), although basal Ca2+ was markedly elevated. In all cases Ca2+ quickly returned to control levels and contractile activity recovered within 5Ð15 min upon removal of cyanide.
These data indicate that metabolic inhibition and hence hypoxia rapidly and profoundly reduces the ability of the uterus to contract, even when agonists are applied. As such these data support a role for hypoxia in dystocic labours. The mechanism of the contractile dysfunction is not entirely explained by changes in [Ca2+], but also point to altered sensitivity of the contractile proteins to Ca2+, possibly as a result of acidosis. The cause of the persistent elevation of basal Ca2+ is not clear, but could be due to impaired mitochondrial Ca2+ handling or Ca2+ efflux mechanisms.
We are grateful to all staff and patients at the Liverpool Women’s Hospital.
All procedures accord with current local guidelines.