The effects of metabolic inhibition on intracellular calcium and contractility of human myometrium

Objective: Hypoxia occurs in the uterus during labour and may contribute to dysfunctional labours. We wanted to establish its effects on pregnant human myometrium and elucidate the mechanisms involved. Design: Scientific study. Setting: University Hospital and laboratories. Population or Sample: Term pregnant women. Methods: We measured contractions and intracellular [Ca ²⁺] ([Ca²⁺]_i), in biopsies from term pregnant women undergoing elective caesarean section, and used cyanide to block oxidative phosphorylation. Main outcome measures: Changes in contractility and calcium. Results: Although basal levels of [Ca²⁺]_i and tone rose, spontaneous and agonist-induced Ca²⁺ transients and phasic contractions were rapidly reduced and abolished by cyanide. Neither stimulation of the uterus with oxytocin nor the Ca channel agonist, Bay K8644, prevented the changes produced by cyanide. The tonic force produced by depolarising the myometrium was also decreased by cyanide, but slowly recovered towards control levels, whereas [Ca²⁺]_i was maintained throughout. Similar data were obtained when nitrogen, rather than cyanide, was applied to the depolarised uterus. Conclusions: Impairment of oxidative phosphorylation is a potent depressor of phasic activity in human myometrium, irrespective of how it is produced, and our data suggest its effects lie at and beyond the surface membrane. Stimulation of the hypoxic uterus was not effective, which may explain the unpredictability of oxytocin application in some dysfunctional labours.