Circulatory responses to acute asphyxia are not affected by the glutamate antagonist lubeluzole in fetal sheep near term.
OBJECTIVE
Asphyxia is one of the main causes of perinatal brain damage that can result in psychomotor deficits during later development. Recently lubeluzole, a new glutamate antagonist, was shown to improve clinical outcome considerably without any safety concerns in adults who had acute ischemic stroke. However, our preliminary experiments showed transient alterations in heart rate as well as arterial hypertension after intravenous application of this compound in fetal sheep. The aim of the present study was to examine in detail whether lubeluzole affects circulatory responses to acute asphyxia in fetal sheep near term.


METHODS
Eleven fetal sheep were chronically instrumented at a mean gestational age of 133 +/- 2 days (term is at 147 days). The fetuses in the study group (n = 6) received three bolus injections of lubeluzole at 30-minute intervals (3 x 0.11 mg/kg estimated body weight), and five controls received solvent. Organ blood flows and physiologic variables were measured before, during, and after arrest of uterine blood flow for 2 minutes (ie, at 0, 1, 2, 3, 4, and 30 minutes).


RESULTS
Before asphyxia, distribution of combined ventricular output and physiologic variables in fetuses from the control group were in the normal range for chronically prepared fetal sheep near term. During acute asphyxia there was a redistribution of cardiac output toward the central organs accompanied by pronounced bradycardia and progressive increase in arterial blood pressure. There were nearly no differences between groups in the time course of physiologic and cardiovascular variables measured before, during, and after acute intrauterine asphyxia.


CONCLUSIONS
Lubeluzole did not affect circulatory responses to acute asphyxia in fetal sheep near term.
Berger
R
R
Department of Obsetrics and Gynecology, University of Bochum, Bochum, Germany. richard.berger@ruhr-uni-bochum.de
Garnier
Y
Y
Löbbert
T
T
Pfeiffer
D
D
Jensen
A
A
D000818:Animals; D001237:Asphyxia / Q000503:physiopathology*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002302:Cardiac Output; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005315:Fetal Diseases / Q000503:physiopathology*; D005865:Gestational Age; D006340:Heart Rate, Fetal; D006439:Hemodynamics; D010880:Piperidines / Q000494:pharmacology*; D011247:Pregnancy; D012756:Sheep; D013844:Thiazoles / Q000494:pharmacology*; D014599:Uterus / Q000098:blood supply
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D013844:Thiazoles; C097722:lubeluzole