Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model

J. B. Craft, N. H. Goldberg, M. Lim, E. Landsberger, P. Mazel, F. P. Abramson, A. L. Stolte, M. E. Braswell, J. P. Farina

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Using the chronic maternal-fetal sheep preparation, nine pregnant ewes were studied to determine the effects of intravenous dantrolene sodium on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Two doses of dantrolene sodium were studied: 1.2 mg/kg and 2.4 mg/kg. After 2.4 mg/kg, maternal cardiac output increased 29% (P < 0.05) after 1 min and returned to normal after 30 min. Maternal mean arterial pressure increased 13% after 1 min and remained significantly elevated (P < 0.01) for 3 h. No significant changes (P > 0.05) were observed in maternal heart rate, uterine artery blood flow, or central venous pressure. Maternal arterial fetal arterial pressure remained unchanged (P > 0.05). Fetal arterial pH declined from 7.42 to 7.39 (P < 0.01) after 1 min and returned to baseline values after 10 min. Fetal heart rate decreased 24% (P < 0.01) after 3 min and returned to normal after 10 min; the mean fetal arterial pressure remained unchanged (P > 0.05). Fetal arterial pH declined from 7.29 to 7.27 (P < 0.05) after 1 min and remained significantly decreased for 120 min. Similar changes of lesser magnitude and shorter duration were seen following the 1.2 mg/kg dose. Maternal levels of dantrolene were less than 3 μg/ml. Although an equilibrium between maternal and fetal plasma dantrolene concentrations was apparent at 5 min, the fetal levels of dantrolene were approximately 10% of the mother's. The results indicate that the administration of intravenous dantrolene at 1.2 mg/kg or 2.4 mg/kg has no clinically significant adverse effect on mother or fetus in the sheep model.

Original languageEnglish (US)
Pages (from-to)68-72
Number of pages5
JournalAnesthesiology
Volume68
Issue number1
StatePublished - 1988
Externally publishedYes

Fingerprint

Dantrolene
Sheep
Mothers
Uterine Artery
Central Venous Pressure
Intravenous Administration
Cardiac Output
Arterial Pressure
Fetus
Heart Rate

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Craft, J. B., Goldberg, N. H., Lim, M., Landsberger, E., Mazel, P., Abramson, F. P., ... Farina, J. P. (1988). Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model. Anesthesiology, 68(1), 68-72.

Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model. / Craft, J. B.; Goldberg, N. H.; Lim, M.; Landsberger, E.; Mazel, P.; Abramson, F. P.; Stolte, A. L.; Braswell, M. E.; Farina, J. P.

In: Anesthesiology, Vol. 68, No. 1, 1988, p. 68-72.

Research output: Contribution to journalArticle

Craft, JB, Goldberg, NH, Lim, M, Landsberger, E, Mazel, P, Abramson, FP, Stolte, AL, Braswell, ME & Farina, JP 1988, 'Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model', Anesthesiology, vol. 68, no. 1, pp. 68-72.
Craft JB, Goldberg NH, Lim M, Landsberger E, Mazel P, Abramson FP et al. Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model. Anesthesiology. 1988;68(1):68-72.
Craft, J. B. ; Goldberg, N. H. ; Lim, M. ; Landsberger, E. ; Mazel, P. ; Abramson, F. P. ; Stolte, A. L. ; Braswell, M. E. ; Farina, J. P. / Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model. In: Anesthesiology. 1988 ; Vol. 68, No. 1. pp. 68-72.
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abstract = "Using the chronic maternal-fetal sheep preparation, nine pregnant ewes were studied to determine the effects of intravenous dantrolene sodium on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Two doses of dantrolene sodium were studied: 1.2 mg/kg and 2.4 mg/kg. After 2.4 mg/kg, maternal cardiac output increased 29{\%} (P < 0.05) after 1 min and returned to normal after 30 min. Maternal mean arterial pressure increased 13{\%} after 1 min and remained significantly elevated (P < 0.01) for 3 h. No significant changes (P > 0.05) were observed in maternal heart rate, uterine artery blood flow, or central venous pressure. Maternal arterial fetal arterial pressure remained unchanged (P > 0.05). Fetal arterial pH declined from 7.42 to 7.39 (P < 0.01) after 1 min and returned to baseline values after 10 min. Fetal heart rate decreased 24{\%} (P < 0.01) after 3 min and returned to normal after 10 min; the mean fetal arterial pressure remained unchanged (P > 0.05). Fetal arterial pH declined from 7.29 to 7.27 (P < 0.05) after 1 min and remained significantly decreased for 120 min. Similar changes of lesser magnitude and shorter duration were seen following the 1.2 mg/kg dose. Maternal levels of dantrolene were less than 3 μg/ml. Although an equilibrium between maternal and fetal plasma dantrolene concentrations was apparent at 5 min, the fetal levels of dantrolene were approximately 10{\%} of the mother's. The results indicate that the administration of intravenous dantrolene at 1.2 mg/kg or 2.4 mg/kg has no clinically significant adverse effect on mother or fetus in the sheep model.",
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