HOSHI Nobuhiko Hokkaido Univ., School of Medicine, Instructor, 医学部, 助手 (10209223)
MATUMOTO Yoshinori Hokkaido Univ.Hospital, Instructor, 医学部附属病院, 助手 (40241335)
OKUYAMA Kazuhiko Hokkaido Univ.Hospital, Instructor, 医学部附属病院, 助手 (40214085)
|Budget Amount *help
¥7,100,000 (Direct Cost : ¥7,100,000)
Fiscal Year 1997 : ¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1996 : ¥3,900,000 (Direct Cost : ¥3,900,000)
In order investigate the mechanisms of initiation of periventricular leukomalacia (PVL), total number sheep fetuses at 110 days of gestation were catheterized in utero and were subjected to chronic in utero preparation experiment. At 113 days of gestation, corresponding to 30 weeks of human pregnancy, hypotension (minimum mean arterial blood pressure ; 25 mmHg) was introduced to fetus by blood extraction (35%) from fetal femoral arrery. Pathological examination of fetal central nervous system (CNS), 72 hours after the systemic hypotension loading, revealed the occurrence of PVL like lesion exactly at periventricular white matter area, exhibiting swelling of axon, focal necrosis, and refractory infiltration of microglia or macrophage cells (6 out of 8 experiments). Immunohistochemistry also disclosed beta-amyloid precursor protein, characteristic feature of PVL.However, there was no macroscopic-nor mictoscopic-evidence of CNS lesion when only anemic insult was loaded to fetuses (control
) experiments, N=3). Because our experiment was designed to avoid fetal hypoxemia and acidosis, we concluded that acute systemic hypotension of fetus at certain gestational stage would lead to fetal CNS hypoperfusion resulting in PVL formation.
Hormonal investigation suggested the possible invplvement of transient elevation of arginine vasopressin (AVP) in the very early stage of PVL formation. We are now trying to elucidate the relationship between hormonal changes and characteristic patterns of fetal heart beat monitoring by means of frequency analysis so that we could prove the dectease of fetal CNS blood flow a ter the hypotension loading and could find the way to predict or detect the dangerous fetal condition to PVL initiation in clinical managements.