Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PL07

Poster Communications

Hypoxia and uterine contractions: Not too much but not too little

S. Wray1

1. University of Liverpool, Liverpool, United Kingdom.

During labour contractions are of such intensity that blood vessels travelling through the uterus are compressed. The myometrium (and the fetus) experiences this intermittent hypoxia and we have shown in vivo that transient decreases of myometrial pH and ATP are associated with each contraction (1). Prolonged myometrial hypoxia and the fall in pH associated with it, can inhibit or even abolish uterine contractions. We have recently found that lactate can reduce myometrial force, pH and intracellular calcium transients (2). These local changes (myometrial capillary blood) are significantly associated with dysfunctional labour, i.e. those characterized by weak contractions, and which is a major cause of unplanned Caesarean section (3). These changes in amniotic fluid lactate are prognostic for difficult labours (4). A conundrum arises associated with these metabolic changes that are part of normal maternal physiology and labour. How in labour, despite repeated, transient episodes of local ischaemia, hypoxia and acidity, do contractions become progressively stronger, increasing in amplitude, frequency and duration over many hours. The mechanism of this vital increased contractility in the face of deleterious metabolic changes is not understood. We have however recently found that repetitive brief periods of hypoxia produce large and sustained increases in contractility, such as occurs in labour, in samples from pregnant but not non-pregnant uterus (5). These findings suggest that ischemic tolerance is an adaptive response of the term uterus and is initiated when contractions reduce uterine blood flow and produce repeated hypoxic stresses. The released metabolites such as adenosine stimulates contractility via increasing Ca entry and stimulating intracellular pathways especially prostaglandin, suggesting the mechanism may be related to hypoxic preconditioning, which is the most powerful mechanism known for limiting infarct size in the heart. These findings also suggest that in women, whose labours are dysfunctional, this inherent mechanism is not working and thus therapeutic strategies to stimulate it would be of benefit. Further work is first required to determine the mechanism of this hypoxia-induced force increase (HIFI) and also to establish if its premature activation can occur and facilitate preterm delivery.

Where applicable, experiments conform with Society ethical requirements