Extracellular Calcium's Role in Carbetocin-Mediated Human Myometrial Contractility Hypothesized to Optimize Uterine Tone

Postpartum hemorrhage (PPH), primarily due to uterine atony, remains a leading cause of maternal morbidity and mortality globally. Current pharmacological management relies on uterotonics like carbetocin, a long-acting oxytocin analog, recommended for PPH prophylaxis. However, calcium, a critical factor for myometrial contractions, can fluctuate at term, with both hypo- and hypercalcemia potentially impairing uterine tone. While oxytocin's efficacy is known to be influenced by calcium levels, the specific role of extracellular calcium in carbetocin-induced contractility remains unexplored, representing a significant gap in optimizing PPH management.

This study is designed as the first ex vivo investigation to assess the impact of extracellular calcium levels on carbetocin-induced contractility in human myometrium. Researchers plan to test myometrial tissue samples under varying extracellular calcium conditions (hypocalcemia, normocalcemia, hypercalcemia). The study will evaluate contractility in both naive myometrium and tissue pretreated with oxytocin to simulate clinical scenarios of desensitization. The primary endpoint will be the measurement of uterine tone and contractility in response to carbetocin across these different calcium environments, utilizing organ bath techniques to quantify force generation.

This abstract describes a study hypothesis and design; therefore, specific results are not yet available. The investigators hypothesize that extracellular normocalcemia will provide superior carbetocin-mediated contractility in both naive and oxytocin-pretreated human myometrium compared to either hypercalcemia or hypocalcemia. The findings, once available, are expected to provide evidence for optimizing carbetocin use in clinical practice.