James Metcalfe

Aortic function during normal human pregnancy

Arterial rupture and dissection have been observed in both normal and complicated pregnancies. To understand how arterial mechanical properties might change during pregnancy, we measured aortic root diameter by M-mode echocardiography and obtained simultaneous cuff blood pressures during systole and diastole at rest and during isometric exercise. Measurements were obtained in 19 women at the end of normal gestation and again 3 to 6 months post partum. The aorta is larger and more compliant during normal human pregnancy, and these changes may not revert to prepregnant levels post partum. Increased aortic compliance, combined with decreased vascular resistance, may enhance left ventricular performance in normal pregnancy. Conversely, the presumed structural alterations leading to increased compliance may weaken diseased vessels leading to dissection or rupture during pregnancy.

Oxygen availability and growth of the chick embryo

Two experiments were performed using White Leghorn eggs incubated in 50% humidity, at 38 degrees centigrade, and an average barometric pressure of 747 Torr. In one experiment, eggs in the experimental group were each half covered with a neoprene membrane, reducing the diffusing capacity by approximately 20%, and incubated in 21% O2. In the second experiment, the experimental eggs were incubated (uncovered) in 60% O2. Control eggs were incubated (uncovered in 21% O2 simultaneously with the experimental eggs in each study. A relationship between egg surface area (calculated from weight of the freshly laid egg) and embryo weight at 18 days was confirmed for all three groups. When comparisons were made among the groups, there was significant retardation of embryonic growth in the half-covered eggs; in contrast, embryos from eggs incubated in 60% O2 were significantly heavier at 18 days that control eggs incubated in air. The fact that embryo growth can be accelerated by incubation of the egg in 60% O2 suggests that the oxygen tension in blood leaving the chorioallantoic capillaries normally limits the rate of embryonic growth for the first 18 days of incubation in this species.

Exercise dynamics in late gestation: Effects of physical training

Heart rate and stroke volume were measured serially in subjects at rest in the sitting position and at the onset and end of a 6-minute period of upright bicycle exercise. Twenty-three subjects with normal pregnancy were studied in late gestation and again post partum. Rest and exercise cardiac outputs in late gestation were not different from those in the postpartum period. Heart rate was higher at rest and stroke volume lower during exercise in late gestation than post partum. At the end of exercise, stroke volume fell dramatically in late gestation but not post partum. Ten women prospectively identified as physically fit had responses that were not different from those of the nonfit cohort in late gestation. Post partum, the physically fit women had exercise responses typical of trained persons and different from those of the nonfit cohort. In late gestation, rest and exercise hemodynamics in subjects in the sitting position appeared to be dominated by factors influencing venous return, independent of physical fitness.

Organ growth in chick embryos incubated in 40% or 70% oxygen

Incubation of eggs in 60% oxygen has been shown to enhance growth of the chick embryo. To determine whether oxygen accelerates growth over a range of concentrations, eggs were incubated in 40% or 70% O2. Control eggs, pair-matched by initial weight, were simultaneously incubated in room air (21% O2). Embryo and organ weights from matched pairs of eggs were compared on incubation days 14, 16 and 18 (40% O2) or 10, 12, 14, 16 and 18 (70% O2). Embryos incubated in 40% O2 displayed a pattern of growth enhancement similar to that previously reported for 60% O2. Accelerated embryonic growth was maintained through day 18. The heart showed the greatest percentage increase in weight over control, exceeding that of the whole embryo on days 16 and 18. The brain displayed significant enhancement only on day 16. Weight of the liver was unaffected by hyperoxia. Embryos in 70% O2 exhibited accelerated growth in all of the tissues examined early in incubation. Growth rate of the hyperoxic embryos then declined, so that embryo weight on day 18 did not differ from control. The brain, heart, eye, and proventriculus plus gizzard from 70% O2 embryos weighed significantly less than controls on day 18. Growth inhibition was most striking in the heart; heart/body weight ratio of 70% O2 embryos was significantly less than control throughout the observation period. The results confirm the growth accelerative effect of oxygen and suggest that the degree of growth enhancement is proportional to the ambient oxygen concentration. Accelerated growth cannot be maintained, however, in 70% O2.

Effect of ambient oxygen on organic phosphate concentrations in erythrocytes of the chick embryo

Abstract Remarkable quantitative and qualitative changes occur in the erythrocytic organic phosphates of the developing chicken. We examined the influence of continuous incubation under hyperoxia (70% oxegyn) on this pattern in the 10–21 day embryo. Hyperoxia had no influence on adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) levels on or before day 14. After day 14, hyperoxia attenuated the fall in ATP and eliminated the transient rise in 2,3-DPG concentrations observed in control embryos. Acute exposure of day 17 embryos to 70% oxygen resulted in similar changes; switching day 17 hyperoxic embryos to 21% oxygen showed the reverse. Acute exposure of day 11 or day 13 embryos to hypoxia (15% oxygen) resulted in a decline in ATP and an increase in 2,3-DPG levels. The ATP and 2,3-DPG concentrations were thus influenced by ambient oxygen although not uniformly throughout embryonic development. Oxygen dissociation curves of erythrocyte suspensions from day 18 embryos showed a lower oxygen affinity for hyperoxic embryos than for controls. The organic phosphate analyses and oxygen binding results are consistent with the hypothesis that the chick embryo is relatively hypoxic during the last third of embryonic development. The results also suggest that late in development, erythrocytes of control embryos respond to the oxygen limitation in a manner that facilitates oxygen uptake by the blood at the shell.

Stimulatory and persistent effect of acute hyperoxia on respiratory gas exchange of the chick embryo

The hypothesis that oxygen availability limits growth of the normal chick embryo late in development predicts that an increase in oxygen availability would accelerate the rate of growth and, therefore, metabolism. We tested the prediction concerning metabolism by comparing the oxygen consumption (VO2) and carbon dioxide production (VCO2) of 14-18 day embryos acutely exposed to either 50% or 100% O2 with those of normoxic (21% O2) controls. Two hours of hyperoxia produced increases in both VO2 and VCO2; however, repeated measurements over time in normoxia also demonstrated a significant increase in gas exchange, presumably due to normal growth of the embryos. After correcting for the increase in VO2 due to growth, there was no effect of 60% O2 on day 14. Thereafter the stimulatory effect of 60% O2 increased gradually, reaching 6.1% on day 18. VCO2 was 4 to 6% higher in embryos acutely exposed to 60% O2 than in normoxic controls throughout the observation period, although the difference was significant only on day 18. The VO2 of embryos acutely exposed to 100% O2 was not significantly different from that observed in 60% O2, and was still significantly elevated 3 h after the eggs were returned to 21% O2. We conclude that acute hyperoxia late in incubation elicits an increase in embryonic VO2 and VCO2, with little or no effect on the respiratory exchange ratio, and that the stimulation of gas exchange by 100% O2 persists after the embryo is returned to normoxic conditions. These findings support the hypothesis that oxygen availability limits growth and metabolism of the normoxic chick embryo late in development.

Respiratory characteristics of maternal and fetal blood in cyanotic congenital heart disease

Abstract Cyanotic congenital heart disease in the pregnant woman is associated with high incidences of maternal and perinatal morbidity and mortality. In the presence of maternal arterial hypoxemia, an elevation in the oxygen-carrying capacity of the blood together with displacemmt to the right of the whole blood oxyhemoglobin dissociation curve facilitates oxygen delivery to the fetus. Although cord blood studies at delivery gave no evidence of intrauterine asphyxia, the presence of chronically limited oxygen supply is suggested by an elevation of hemoglobin concentration in cord blood and the low weight for gestational age of th ese infants at birth.

The effect of oxygen on growth and development of the chick embryo

When eggs are incubated in 60% O2; the weight of the 18-day embryo is greater than that of the control incubated in 21% O2,. Conversely, when O2 availability is reduced by covering part of the eggshell, embryonic growth is retarded. The weight of the embryo at day 18 correlates with the surface area of its egg, as does the diffusing capacity for O2 and the calculated chorioallantoic capillary surface area. Furthermore, during the last few days of chorioallantoic respiration in 21% O2, the embryo becomes hypoxemic and its rate of growth slows. We propose that the O2 tension in blood leaving the chorioallantoic capillaries limits the rate of growth of the chick embryo until the onset of pulmonary respiration.

Stimulation of growth of the chick embryo by acute hyperoxia

We have previously demonstrated that continuous incubation in elevated concentrations of ambient oxygen leads to accelerated growth of the chick embryo. We now report that a similar growth response is elicited by acute (72 h) exposure beginning on the 16th day of incubation. White Leghorn eggs were paired by initial weight and incubated in air for 15 days in forced-draft incubators. Embryos were sampled on days 11, 13 and 15 (experiments 1, 2, 3) or 13, 14 and 15 (experiment 4), freed of all extra-embryonic membranes and weighed. On day 16 the experimental group was switched to 60% O2. The control group was maintained in air. A portion of the remaining eggs from each group was opened on days 16, 17 and 18 (experiment 4), or alternatively all the remaining eggs were opened at the end of the 18th day of incubation (experiments 1, 2, 3). Linear regression analysis of growth curves obtained by plotting log wet embryo weight (g) vs log incubation age (d) showed a significantly greater rate of growth (slope) for days 15-18 in embryos exposed to 60% O2. These results support the hypothesis that growth of the chick embryo is normally limited by the availability of oxygen.

Congenital arteriovenous fistula and pregnancy: Report of three cases

Abstract 1. Three instances of congenital pelvic fistulas complicating pregnancy with pertinent medical studies and obstetrical and surgical procedures are reviewed. 2. The limited number of observations of this condition recorded in the literature make all conclusions tentative. Nevertheless, it appears that a congenital pelvic arteriovenous fistula is a nonhereditary nonfamilial lesion, not as rare as the few reports suggest. 3. The size and symptomatology may increase with age and repeated advanced pregnancies. It may be the cause of antepartum bleeding, postpartum hemorrhage, and premature labor but not fetal anomalies. 4. Arteriovenous aneurysm is a justification for contraception or even sterilization in multiparas, and, in the presence of pregnancy, a possible indication for therapeutic abortion or delivery by cesarean section. 5. The condition is often best palliated until serious symptomatology threatens; whereupon radical surgical correction under the best auspices should be arranged. It is generally not amenable to operation during pregnancy, although interruption of the lymphogastric vasculature may prevent excessive blood loss.