Ming-Neng Yeh

Reduced uterine blood flow and fetal hypoxemia with acute maternal stress: Experimental observation in the pregnant baboon

The effects of maternal hyperexcitability on the fetus were studied in 17 baboons. In the period of agitation, induced by stressful stimulus such as exposure to bright light or by clamping of the toe, the mother exhibited an increase in arterial blood pressure and, in some instances, arrhythmia. These changes were accompanied by an increased uterine activity and reduced uterine blood flow, and resulted in a decrease in heart rate and arterial oxygenation in all fetuses. Fetal recovery was prompt after maternal agitation was terminated, either by removal of the stimulus or by sedation with pentobarbital or nitrous oxide. This sedation also prevented a decrease in uterine blood flow when stress was repeated.

Pulsatile administration of gonadotropin-releasing hormone for induction of ovulation

Chronic pulsatile administration of gonadotropin-releasing hormone (GnRH) was used to induce ovulation in 12 women with various ovulatory disorders. In the first group of eight patients with normal to low baseline levels of gonadotropin, seven responded favorably to the treatment. Follicular maturation was observed in 57% of the treated cycles, and normal ovulatory cycles were induced in 24% of the patients. Two patients became pregnant. The intravenous route of administration was more effective than the subcutaneous one, possibly in response to the GnRH profile after each pulse. (The amplitude of GnRH peaks after an intravenous pulse was four times that seen after a subcutaneous one.) In contrast, follicular maturation and ovulation could not be induced in four women of a second group of patients with normal baseline levels of follicle-stimulating hormone but with high and frequent pulses of luteinizing hormone. The conclusion reached was that pulsatile administration of GnRH can be a new therapeutic tool in the treatment of ovulatory disorders in women who have an insufficient endogenous release of GnRH.

Umbilical vein occlusion and transient acceleration of the fetal heart rate. Experimental observations in subhuman primates.

Transient acceleration of the fetal heart rate is commonly seen in the cardiotachometer tracing of the human fetus during labor. A likely cause appeared to be partial occlusion of the umbilical cord. On the basis of this hypothesis, fetal cardiovascular responses to partial occlusion of the umbilical cord or isolated intra-abdominal portion of umbilical vein were studied in near-term pregnant baboons and rhesus monkeys prior to and following sympathetic blockade with dibenzyline and propranolol. The responses were of two types. In the well-oxygenated fetus, partial occlusion resulted in transient acceleration of heart rate and a decrease in pulse pressure. This response was abolished with dibenzyline or propranolol. In the hypoxic fetus, partial occlusion resulted in either bradycardia and hypotension or hypotension with no alteration in heart rate. Thus, transient acceleration of the fetal heart rate can be explained on the basis of a sympathetic response to diminished venous return. It would appear to be an early sign of a potential cord complication. This response will not be seen if the fetus becomes asphyxiated and hypoxic.

Renal response of fetal lamb to complete occlusion of umbilical cord

The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure.

Myocardial conduction defects in association with compression of the umbilical cord. Experimental observations on fetal baboons.

Experiments have been performed in 16 pregnant baboons to study in greater detail the fetal hemodynamics, heart rate, and acid-base changes during occlusion of the umbilical cord. A total of 32 observations were made during which the umbilical cord was completely occluded with the fetus intact in utero; 11 were made after the intravenous administration of atropine, 0.01 to 0.02 mg. per kilogram, to fetus. Various degrees of conduction defects occurred in 17 of 21 observations before atropine. Complete atrioventricular block with extrasystoles was seen six times. Upon release of cord occlusion, there was a rapid recovery of myocardial conduction. Atropine prevented myocardial conduction defects; bradycardia was less and the onset was delayed. These observations suggest that myocardial conduction defects which occur during the course of cord occlusion are due to parasynpathetic stimulation. They could also be due to an increased sensitivity of the fetal myocardium to acetylcholine under hypoxic conditions. No recommendation can be made at the present time with regard to the administration of atropine to the fetus when cord compression is suspected on clinical grounds.

Renal response of the lamb fetus to partial occlusion of the umbilical cord

The role of the fetal kidney during impairment of placental exchange was studied in eight fetal lambs, intact in utero; a standard asphyxial insult for a period of 1 hour was produced by occluding the umbilical cord sufficiently to lower the fetal heart rate by 35 +/- 5 beats/min and the pH by 0.15 units. This asphyxial stress caused a fall in urine output from a control of 0.17 to 0.03 ml/kg/min and of glomerular filtration rate from 1.2 to 0.3 ml/min; release of the occlusion was followed by mild diuresis. The fall in urine output was accompanied by a rise in total primary solutes including concentrations of electrolytes; this rise continued for 1 to 2 hours following the release of the occlusion. Because of the low urinary output during the period of occlusion, there was a fall in excretion of electrolyte; an increase in net acid excretion occurred only after the release of the cord. These experiments show that, although the fetal kidney is capable of contributing to elimination of acid following compression of the cord, there may be an associated net loss of water and electrolytes.

Effect of hypoxemia and acidemia on the fetal cardiac response to acetylcholine: experimental observations in fetal baboons.

The effect of hypoxemia and acidemia on the fetal cardiac response to acetylcholine (ACh) was studied in 24 baboon fetuses in utero. A bolus injection of ACh was given intravenously to the fetus at a dose that ranged from 5 to 160 micrograms/kg of estimated fetal weight. The responses were divided into two groups according to fetal oxygenation and acid-base state. Fetuses in group I were well oxygenated (PaO2, 31 +/- 1.4 mm Hg; pHa, 7.32 +/- 0.154; only five atrioventricular (A-V) heart blocks were induced with 50 +/- 3.3 micrograms/kg of ACh. Fetuses in Group II were hypoxemic (PaO2, 18 +/- 1.2 mm Hg) and acidemic (pHa, 7.05 +/- 0.048); ten A-V heart blocks were induced with a comparable dose of ACH (45 +/- 6.8 micrograms/kg). Dose response relationship is noted in individual fetuses with multiple dosage injections. These findings suggest that the fetal cardiac response to ACh is both dose related and more profound when the fetus is hypoxemic and acidemic, and indicate that the hypoxic and acidotic fetus is at a greater risk from strong stimulation of the parasympathetic nervous system. Atropine prevented myocardial conduction defect induced by intravenous injection of ACh even in the severely hypoxemic baboon fetus. This observation suggests that judicious use of atropine could be a life-saving measure when a prolonged severe degree of cord occlusion is suspected.