Inefficient uterine activity leads to prolongation of labour and causes increased morbidity and mortality to both mother and child. During each contraction the reduction in blood flow produces localised hypoxia and stimulation of anaerobic metabolism, resulting in alteration of metabolites such as ATP and P_i and a decrease in pH. Hypoxia and acidification reduce the spontaneous contractile activity of rat myometrium but there is only very limited data on their effects on human myometrium, e.g. changes in [Ca²⁺]_i, the main determinant of uterine force, are unknown. We have therefore investigated the effects of both hypoxia and acidification on contractions and calcium in human myometrium.

Human, non-labouring myometrium, obtained with ethical approval and informed consent, from elective cesarean sections at term, was dissected into strips and loaded with indo-1. Hypoxic conditions were simulated with cyanide (2 mM) and changes in pH_i produced by iso-osmotic substitution (40 mM) of NaCl with weak acid, sodium butyrate. Statistical analysis was performed on paired data using Student’s t test (95 % confidence). Values represent means ± S.E.M., and n is the number of samples.

Spontaneous intracellular calcium transients and contractions were significantly reduced and ultimately abolished, by both hypoxia (n = 7) and acidification (n = 4), although both conditions caused basal calcium to rise significantly (hypoxia, 133 % ± 11; acidification, 112 % ± 1).

Oxytocin was used to assess whether agonist-induced contractions are more resistant to the effects of acidification (n = 6) or hypoxia (n = 8); the data were similar to those found during spontaneous activity, i.e. force and Ca²⁺ transients were abolished. Basal Ca²⁺ was increased significantly in all cases (hypoxia, 187 ± 29% acidification, 108.7 ± 0.67 % compared to control (100 %)).

Clinically, oxytocin is used to augment labour, so we investigated whether the application of oxytocin to hypoxic or acidic myometrium could restore tone and [Ca²⁺]_i. No significant effect was seen with hypoxia or acidification although 1/7 under acidic conditions showed some recovery.

Both hypoxia and acidification are found to be potent inhibitors of human myometrial contraction. Although experimentally acidification was faster acting, both were very similar in their effects. The reduction in the Ca²⁺ transient also suggests a shared mechanism of action, i.e. inhibition of L-type Ca²⁺ entry. The basal calcium rise may be due to release from intracellular organelles. Oxytocin is unable to augment contractions in tissues with underlying hypoxaemia or acidosis. Possibly, the anaerobic metabolism occurring during prolonged labours, underlies the clinical finding that oxytocin is not always efficacious in slow labours.

S.J.P. is supported by an Action Research Clinical Training Fellowship, E.M.-B. is supported by the Libyan Government.