| Co-Investigator(Kenkyū-buntansha) |
MORITA Shigeki Kyushu University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (70243938)
NISHIDA Takahiro Kyushu University, Kyushu University Hospital, Research Associate, 大学病院, 助手 (50284500)
TOKUNAGA Shigehiko Kyushu University, Kyushu University Hospital, Research Associate, 大学病院, 助手 (80346775)
TANOUE Yoshihisa Kyushu University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 助手 (40372742)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Background : Previously, endothelial dysfunction of the umbilical artery due to fetal cardiac bypass has been reported. Here, the effect ofendothelin receptor blocker on the endothelialfunction of the umbilical artery and the placental function was investigated. Methods : Twenty one fetal lambs were divided into a control group (Group C;n=7), apump group (Group P;n=7) and a pump with endothelin blocker group (Group E;n=7). In group P and group E, cardiac bypass was maintained for 30 minutes using a low priming circuit with a centrifugal pump. In group E, endothelin-1 receptor blocker, TKA-044 (3 mg/hour) was administered to the fetus during the experiment. Hemodynamic measurements and blood gas analyses were performed before, during, and 30 and 60 minutes after the bypass in the pump group. The umbilical artery was harvested 60 minutes after cessation of the bypass. Endothelium-dependent relaxation (bradykinin(BK), calcium ionophore (A231I87)) and endothelium-independent relaxation (so
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dium nitroprusside) were measured after smooth muscle contraction by 60 mM potassium or serotonin and compared between the two groups. Results : Endothelium-dependent relaxation was impaired in group P compared with group C either by BK (60 mM K : group C;42.7±3.7%, group P;23.0±3.6%, p=0.0023; -HT : group C;43.6±6.4%, group P;18.9±2.5%, p=0.0022) or by A23187 (60 mM K:group C;53.8±6.9%, group P;20.9±3.6%, p=0.0011;5-HT : group C;37.8±1.5%, group P;19.6±3.9%, p=0.0093). Endothelin receptor blocker attenuated this impairment (BK:60 mK;41.6±8.6%,5-HT;46.3±4.1%, A23187:60 mK;37.0±8.3%,5-HT;35.4±7.3%). Meanwhile, endothelium-independent relaxation was preserved in all groups. The umbilical artery flow and aortic pressure of the fetus were similarly decreased at 30 and 60 minutes after the bypass in group P and group E.Hypoxia, hypercapnia and metabolic acidosis progressed during and after the bypass independent of endothelialfunction. Conclusions : Fetal cardiac bypass certainly caused endothelial dysfunction of the umbilical artery and hemodynamic deterioration due to metabolic acidosis. Endothelin-1 receptor blocker prevented endothelial dysfunction but not placental dysfunction. Endothelial dysfunction of the umbilical artery afterfetal cardiac bypass did not play an important role of placental dysfunction Less
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