title: Possible neuroprotective properties of flunarizine infused after asphyxia in fetal lambs are not explained by effects on cerebral blood flow or systemic blood pressure.
abstract: Neuroprotective properties of the calcium channel blocker flunarizine have been reported after hypoxic-ischemic insults in immature, infant, and adult rats. However, its effect on fetal regional cerebral blood flow (rCBF) and systemic blood pressure after severe asphyxia is not known. In 15 fetal lambs (3 to 5 d after surgery; gestational age at the experiment, 123.2 +/- 2.5 d), arterial oxygen content was progressively reduced to 30% by restriction of uterine blood flow with an inflatable balloon occluder around the maternal common internal iliac artery. The rCBF was measured with radioactive microspheres at baseline condition, after 1 h of severe asphyxia, and at 30 and 120 min in the recovery phase. Immediately after the end of the occlusion period, fetuses randomly received either flunarizine or its solvent (0.5 mg/kg estimated fetal weight). No differences in rCBF changes between groups were observed during and after asphyxia. Changes in arterial blood pressure or fetal heart rate due to flunarizine could not be demonstrated either. Only five fetuses (33%) survived this degree of asphyxia longer than 24 h: four of the flunarizine-treated group and one of the control group. It is unlikely that this possible protective property of the drug is caused by its influence on rCBF, arterial blood pressure, or fetal heart rate in the phase immediately after asphyxia.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital, Maastricht, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: de Haan
authors.forename: J L
authors.initials: JL
authors.lastname: Van Reempts
authors.forename: M
authors.initials: M
authors.lastname: Borgers
authors.forename: J
authors.initials: J
authors.lastname: de Haan
authors.forename: J S
authors.initials: JS
authors.lastname: Vles
authors.forename: T H
authors.initials: TH
authors.lastname: Hasaart
mesh_terms: D000137:Acid-Base Imbalance / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D001794:Blood Pressure; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications / Q000188:drug therapy*; D005444:Flunarizine / Q000494:pharmacology / Q000627:therapeutic use*; D005865:Gestational Age; D011247:Pregnancy; D012756:Sheep
chemical_list: D005444:Flunarizine