Basic studies on the theophylline therapy for IUGR pregnacy.
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Utero placental blood flow (UPBF) and placental function is important for fetal growth.In an attempt to accelerate UPBF and placental function of IUGR pregnant rat model, I tried theophylline administration as a new therapy.Rat IUGR model was made by actinomycin-D (AcD) method (AcD 0.07μg/g was injected intraperitoneally to pregnant rats on 14th day of gestation) or made by microspheres (Msp) method (Msp was injected into abdominal aorta to decrease placental blood flow on the 18th day of gestation).Then, at the 16-20th day or 18-20th day of gestation, the IUGR model rats were administered twice a day with 2.5mg of Th (AcD+Th group or Msp+Th group) or 2.5ml of saline (AcD+saline group or Msp+saline group).The following result was obtained:1) At the 20th day of gestation the fetal weight was significantly lower in AcD+saline group or in Msp+saline group than control group (control 4.42g, AcD+saline group 3.91g, Msp+saline group 3.21g), and markedly recovered by Th administration (AcD+Th group 4.41g, Msp+Th group 3.66g).2) Compaired weth controls, IUGR rats had a poor placental blood flow (control 0.89 ml/min, AcD+saline group 0.63 ml/min, Msp+saline group 0.38 ml/min, P<0.001), and had the significant recoveries of that blood flow by Th administration (AcD+Th group 0.99ml/ min, Msp+Th group 0.53ml/min, P<0.001).3) Placental c-AMP was significantly lower (P<0.05) in AcD+saline group (204±53p moles/mg protein) compaired with normal pregnancy (316±68p moles) and recovered to 255±34p moles in AcD+Th group.4) Spontaneous uteine contraction was inhibited at the5×10-3mg/ml or more of Thadministration.5) Via placental maternal transport of 3H-glucose and 14C-α-aminoisobutyric acid (AIB) was lower in AcD+saline group (19.1%, 21.5%) than normal control group.Recovery rates of these transport in Th series were 13.5%, 16.5% in AcD+Th group.6) Aminophylline (250mg, 10minutes) was infused venously to 6 pregnant women at 3rd trimester, and 7 women at delivery. Fetal heart function was increased in rate and in varia bility but maternal heart rate and blood pressure had no change.These data suggested that Th is useful drug for the treatment of IUGR pregnancy.
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