BJOG : an international journal of obstetrics and gynaecology · 2025
Propranolol and Oxytocin-Induced Contractility in Gravid Human Myometrium: An Ex Vivo Laboratory Study.
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Balki Mrinalini, Miller Lauren M, Caliaperumal Jayalakshmi, Wang Stella, Huszti Ella, Kingdom John C
Аннотация
OBJECTIVE: To determine the effect of propranolol on myometrial contractions induced by low dose and high dose oxytocin.
DESIGN: Prospective ex vivo laboratory study.
SETTING: Mount Sinai Hospital, Toronto.
POPULATION: Full-term parturients who underwent elective caesarean deliveries (CD).
METHODS: Two models were developed in the organ bath chamber using myometrial samples obtained during CDs: (i) Labor induction-augmentation model with low-dose oxytocin consisting of 3 groups with the administration of propranolol before and during simulated labor, and a control group. (ii) Postpartum haemorrhage (PPH) model with high-dose oxytocin consisting of 4 groups with the administration of propranolol during and/or after augmented labor (desensitised with oxytocin), and a control group.
MAIN OUTCOME MEASURES: Myometrial contractility was recorded using force transducers.
RESULTS: In the labor induction-augmentation model, propranolol pre-treatment produced a higher area under the curve (AUC) of myometrial contractility induced by low-dose oxytocin (relative percentage difference [diff]: 20.4%; 95% CI [1.4%, 43.2%], p = 0.035) compared to control; however, no difference was observed when propranolol was given after the initiation of labor. In the oxytocin-desensitised PPH model, the AUC of myometrial contractility induced by high-dose oxytocin was improved with propranolol pre-treatment (diff 25.4% [0.2%, 56.8%], p = 0.048), co-treatment (diff 26.7% [3.7%, 54.7%], p = 0.02), and both pre- and co-treatment (diff 28.4% [7.0%, 54.1%], p = 0.007) when compared to the control group.
CONCLUSIONS: Our ex vivo study suggests that propranolol can augment uterine activity by approximately 20%-25% when administered early during labor induction and augmentation. Clinical studies are warranted to determine the relevance of these findings in vivo.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03434444; https://clinicaltrials.gov/.
DESIGN: Prospective ex vivo laboratory study.
SETTING: Mount Sinai Hospital, Toronto.
POPULATION: Full-term parturients who underwent elective caesarean deliveries (CD).
METHODS: Two models were developed in the organ bath chamber using myometrial samples obtained during CDs: (i) Labor induction-augmentation model with low-dose oxytocin consisting of 3 groups with the administration of propranolol before and during simulated labor, and a control group. (ii) Postpartum haemorrhage (PPH) model with high-dose oxytocin consisting of 4 groups with the administration of propranolol during and/or after augmented labor (desensitised with oxytocin), and a control group.
MAIN OUTCOME MEASURES: Myometrial contractility was recorded using force transducers.
RESULTS: In the labor induction-augmentation model, propranolol pre-treatment produced a higher area under the curve (AUC) of myometrial contractility induced by low-dose oxytocin (relative percentage difference [diff]: 20.4%; 95% CI [1.4%, 43.2%], p = 0.035) compared to control; however, no difference was observed when propranolol was given after the initiation of labor. In the oxytocin-desensitised PPH model, the AUC of myometrial contractility induced by high-dose oxytocin was improved with propranolol pre-treatment (diff 25.4% [0.2%, 56.8%], p = 0.048), co-treatment (diff 26.7% [3.7%, 54.7%], p = 0.02), and both pre- and co-treatment (diff 28.4% [7.0%, 54.1%], p = 0.007) when compared to the control group.
CONCLUSIONS: Our ex vivo study suggests that propranolol can augment uterine activity by approximately 20%-25% when administered early during labor induction and augmentation. Clinical studies are warranted to determine the relevance of these findings in vivo.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03434444; https://clinicaltrials.gov/.