Tags

Type your tag names separated by a space and hit enter

Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity.
Teratology. 1992 Nov; 46(5):485-97.T

Abstract

The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h. After 8 h, vascular disruption occurred with hemorrhages. At 24-48 h after dosing, mesenchymal necrosis and, on some occasions, amputation of digits was observed. In the craniofacial region, well-defined superficial hemorrhage was seen in the frontal and nasal region at 8 h. Histologically, subectodermal hemorrhage caused by vascular disruption and microfocal mesenchymal necrosis was observed. At 48 h, some fetuses showed severe diffuse intracranial and superficial hemorrhage, resulting in massive tissue damage, also in the central nervous system (CNS). Maternal heart rate, blood pressure, PO2, and PCO2 were also measured in awake pregnant rabbits 6 h after the last dose on day 16 after daily administration with 150 mg/kg during gestational days 14-16. An attempt was also made to measure fetal heart rate in anesthetized rabbits. The maternal heart rate and blood pressure decreased with about 15% in phenytoin-treated animals, resulting in a decrease in PO2 (approximately 15%) and an increase in PCO2 (approximately 15%). A decrease in fetal heart rate was also registered. The results thus indicate that phenytoin exerts its teratogenic effects by inducing fetal hypoxia, leading to vascular disrupture and necrosis of existing and developing structures.

Authors+Show Affiliations

AB Astra, Södertälje, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1462253

Citation

Danielson, M K., et al. "Histopathological and Hemodynamic Studies Supporting Hypoxia and Vascular Disruption as Explanation to Phenytoin Teratogenicity." Teratology, vol. 46, no. 5, 1992, pp. 485-97.
Danielson MK, Danielsson BR, Marchner H, et al. Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity. Teratology. 1992;46(5):485-97.
Danielson, M. K., Danielsson, B. R., Marchner, H., Lundin, M., Rundqvist, E., & Reiland, S. (1992). Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity. Teratology, 46(5), 485-97.
Danielson MK, et al. Histopathological and Hemodynamic Studies Supporting Hypoxia and Vascular Disruption as Explanation to Phenytoin Teratogenicity. Teratology. 1992;46(5):485-97. PubMed PMID: 1462253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity. AU - Danielson,M K, AU - Danielsson,B R, AU - Marchner,H, AU - Lundin,M, AU - Rundqvist,E, AU - Reiland,S, PY - 1992/11/1/pubmed PY - 1992/11/1/medline PY - 1992/11/1/entrez SP - 485 EP - 97 JF - Teratology JO - Teratology VL - 46 IS - 5 N2 - The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h. After 8 h, vascular disruption occurred with hemorrhages. At 24-48 h after dosing, mesenchymal necrosis and, on some occasions, amputation of digits was observed. In the craniofacial region, well-defined superficial hemorrhage was seen in the frontal and nasal region at 8 h. Histologically, subectodermal hemorrhage caused by vascular disruption and microfocal mesenchymal necrosis was observed. At 48 h, some fetuses showed severe diffuse intracranial and superficial hemorrhage, resulting in massive tissue damage, also in the central nervous system (CNS). Maternal heart rate, blood pressure, PO2, and PCO2 were also measured in awake pregnant rabbits 6 h after the last dose on day 16 after daily administration with 150 mg/kg during gestational days 14-16. An attempt was also made to measure fetal heart rate in anesthetized rabbits. The maternal heart rate and blood pressure decreased with about 15% in phenytoin-treated animals, resulting in a decrease in PO2 (approximately 15%) and an increase in PCO2 (approximately 15%). A decrease in fetal heart rate was also registered. The results thus indicate that phenytoin exerts its teratogenic effects by inducing fetal hypoxia, leading to vascular disrupture and necrosis of existing and developing structures. SN - 0040-3709 UR - https://www.unboundmedicine.com/medline/citation/1462253/Histopathological_and_hemodynamic_studies_supporting_hypoxia_and_vascular_disruption_as_explanation_to_phenytoin_teratogenicity_ L2 - https://doi.org/10.1002/tera.1420460513 DB - PRIME DP - Unbound Medicine ER -