In vivo dilatation of the ductus arteriosus by Rho kinase inhibition in the XXXX .

@entity35 @entity8232 @entity1576
BACKGROUND: @entity8232 , a Rho kinase inhibitor, was reported to dilate the constricted ductus arteriosus in vitro, and was suggested as a neonatal bridge to heart surgery. OBJECTIVES: To clarify the in vivo effectiveness of @entity8232 to dilate the neonatal ductus arteriosus, and its usefulness as a bridge to heart surgery. METHODS: We studied the dose and timing of administration of @entity8232 in the neonatal @entity35 . Postnatal ductal closure was studied on the 21st gestational day following cesarean section and incubation for 30-480 min in room air at 33 degrees C, with a rapid whole-body freezing method. In control @entity35 , the ductus closed rapidly after birth, and the ductal diameter was 0.80 and 0.12 mm at 0 and 30 min after birth. @entity8232 was injected peritoneally into the neonate, and the ductus was studied 30 min after injection and 60 min after birth. RESULTS: @entity8232 , 10 mg/kg, injected within 5 min after birth, dilated the ductus completely to 0.8 mm, and the dose used clinically, 1 mg/kg, dilated the ductus to 0.4 mm. The ductus-dilating effect of @entity8232 decreased rapidly as the neonatal ductus constricted. @entity8232 , 100 mg/kg, dilated the ductus completely, but induced severe @entity1576 and frequent death in 1-hour-old @entity35 . CONCLUSIONS: @entity8232 dilates the neonatal ductus arteriosus dose-dependently in the @entity35 . @entity8232 in large doses dilates the neonatal ductus completely, but is associated with fatal side effects, including @entity1576 .
