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Biomedical subjects

M J Novy

Publications and source records attributed to M J Novy.

At least 91 records · Page 5Linked to original sources

Placental diffusing capacity and its relation to fetal growth.

The placental diffusing capacity for carbon monoxide was measured in unanaesthetized monkeys (M. Mulatta). Maternal and fetal blood was sampled from chronically placed catheters while the mother breathed 50 or 100 parts per million of CO. Diffusing was calculated from the amount of CO taken up by the fetus divided by the partial pressure difference across the placenta, it averaged 0.646 plus or minus 0.062 (SEM) ml x min(-1) x torr(-1) x kg(-1) of fetal weight. The significance of this index of respiratory gas exchange in the monkey placenta is discussed with respect to previous measurements in other species and with respect to fetal growth.

Animals↗

Endocrine and pharmacological factors which influence the onset of labour in rhesus monkeys.

Indomethacin administration in late pregnancy prolonged gestation in caged rhesus monkeys and inhibited premature labour and postponed delivery in chronically catheterized monkey fetuses. Chronic indomethacin treatment was associated with a reduction in the urinary excretion of a prostaglandin metabolite, a potent inhibitory effect on myometrial cyclic AMP phosphodiesterase, and severe oligohydramnios in pre-term and post-term fetuses. Experimental anencephaly (functional hypophysectomy) of the rhesus fetus results in lowered concentrations of maternal oestradiol and loss of the precise control of gestational length, with 40% of fetuses delivering beyond term. Corticotropin (ACTH) infused into the fetus results in raised concentrations of fetal and maternal cortisol, progesterone and oestrogens. Progesterone concentrations in peripheral blood apparently have little bearing on uterine quiescence in the rhesus monkey, since the concentrations of progesterone in maternal and fetal blood vary directly with uterine activity. The results of chronic infusion of corticotropin in the fetal monkey support the theory that in the monkey parturition is mediated by increased oestrogen production by the fetoplacental unit and by a rise in the concentrations of oestrone and prostaglandin in the amniotic fluid.

Adrenocorticotropic Hormone↗

Effect of Indomethacin on cyclic AMP phosphodiesterase activity in myometrium from pregnant rhesus monkeys.

Our results indicate that indomethacin inhibits cyclic AMP phosphodiesterase in the myometrium of the pregnant rhesus monkey under in vitro as well as in vivo conditions. Kinetic data on extracts of myometrium from pregnant rhesus monkeys indicated two cyclic AMP phosphodiesterase activities. The apparent Km value for the high affinity enzyme averaged 3.9 muM and for the low affinity enzyme 23 muM; the Vmax values averaged 0.56 and 1.4 nmoles cyclic AMP hydrolized per mg protein min-1 respectively. When indomethacin was added to the myometrial extracts, the activity of the high Km phosphodiesterase was competitively inhibited, with an average Ki of 200 muM; the low Km enzyme was noncompetitively inhibited with an average Ki of 110 muM. Experiments on myometrial slices demonstrated that 10 muM indomethsacin potentiated the effect of PGE1 and epinephrine on cyclic AMP levels, presumably by inhibiting the phophodiesterase activity. The uterine relaxing effect of indomethacin is generally attributed to the inhibition of prostaglandin synthetase activity. However, treatment of pregnant rhesus monkeys with therapeutic doses of indomethacin resulted in a significant inhibition of myometrial cyclic AMP phosphodiesterase activity in association with uterine relaxation and prolongation of gestation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of indomethacin on corpus luteum function and pregnancy in rhesus monkeys.

Indomethacin was administered during the luteal phase of the menstrual cycle and during late pregnancy in rhesus monkeys. The plasma indomethacin concentrations achieved were within the ranges effective in inhibiting the microsomal prostaglandin synthetase, even when allowances were made for 90% binding to plasma proteins. There were no significant differences in duration of the luteal phase of menses or in luteal phase progesterone concentrations with indomethacin treatment. Our findings do not support the hypothesis that endogenous prostaglandins are important luteolysins in primates. They provide indirect evidence that administration of prostaglandin synthetase inhibitors would have no therapeutic benefit in treatment of the "short luteal phase" syndrome in women. Indomethacin administration in late pregnancy had a significant effect in prolonging gestation. Uteri of treated animals remained flaccid and distended after fundal hysterotomy and removal of fetuses. Maternal plasma concentrations of unconjugated estradiol, estrone, and progesterone during indomethacin treatment were within the expected ranges for late pregnancy in rhesus monkey, although in two animals we found transient, unexplained, high concentrations of estrone in maternal plasma. Chronic indomethacin administration was associated with continuing fetal and placental growth, a 50% fetal mortality rate, oligohydramnios, and meconium staining, and maternal anemia but normal bleeding times. Severe oligohydramnios was noted in preterm as well as post-term fetuses, indicating that indomethacin per se alters regulation of amniotic fluid volume.

Amniotic Fluid↗

Uterine contractility and regional blood flow responses to oxytocin and prostaglandin E2 in pregnant rhesus monkeys.

The effects of oxytocin and prostaglandin E2 (PGE2) infusions on regional blood flow (measured by radioactive microspheres) and myometrial contractility were studied in 18 pregnant rhesus monkeys near term. We observed no significant differences between PGE2 and oxytocin in cardiac output, hemodynamics, or uterine activity. Their effects on the regional distribution of systemic blood flow were similar although the gastrointestinal tract received an increased percentage of cardiac output after PGE2. A relative placental ischemia, together with a myometrial hyperemia, was observed during labor. Uterine contraction produced a large reduction (average 73 per cent) in placental blood flow whereas myometrial blood flow was maintained or sometimes increased. A significant negative correlation was observed between intra-amniotic pressure and placental blood flow. During uterine relaxation, placental flow partially recovered whereas myometrial flow nearly doubled the prelabor values. We conclude that (1) in the dose ranges studied, oxytocin and PGE2 produce similar effects on myometrial contractility and uteroplacental blood flow, and (2) the vascular beds of the placenta and myometrium respond differently to labor of moderate intensity.

Amniotic Fluid↗