Nancy D. Binder

Insulin infusion with parenteral nutrition in extremely low birth weight infants with hyperglycemia

From Nov. 7, 1983, to Nov. 6, 1986, all infants with birth weight less than or equal to 1000 gm admitted to Oregon Health Sciences University who had persistent hyperglycemia and glycosuria were treated with graded insulin infusion while energy intake was increased to at least 100 kcal/kg/day (419 kilojoules/kg/day). The records of these infants were reviewed to define the clinical characteristics of infants likely to develop hyperglycemia and to see whether insulin administration would allow goals for energy intake to be met. There were 76 surviving infants; 34 received insulin and 42 did not. Treated infants were smaller (767 +/- 161 vs 872 +/- 98 gm; p = 0.0004), were more immature (26.8 +/- 1.4 vs 27.7 +/- 2.0 weeks; p = 0.0115), and required mechanical ventilation longer (28 +/- 19 vs 17 +/- 15 days; p = 0.0196). There were no significant differences between the groups at 3, 7, 10, or 14 days for intravenously administered glucose or for total nonprotein energy intake at 3, 7, 10, 14, 28, or 56 days. Treated infants achieved an intake of 100 kcal/kg/day (419 kilojoules/kg/day) at 15 +/- 8 vs 17 +/- 11 days and regained birth weight at 12 +/- 6 vs 13 +/- 6 days (NS). There was no difference in percent change from birth weight at 7, 14, 28, or 56 days. Treated infants had a glucose concentration of 195 +/- 60 mg/dl (10.8 +/- 3.3 mmol/L) while receiving 7.9 +/- 3.0 mg/kg/min (43 +/- 17 mumol/kg/min) of glucose at the start of insulin infusion on days 1 to 14. Insulin was given for 1 to 58 days. The initial dose was 40 to 100 mU/gm of dextrose infused (57 to 142 nmol/mol) and then gradually decreased. Less than 0.5% of blood glucose values were 25 to 40 mg/dl (1.4 to 2.2 mmol/L). We conclude that insulin infusion improves glucose tolerance in extremely low birth weight infants and allows hyperglycemic infants to achieve adequate energy intake similar to that of infants who do not become hyperglycemic.

Myoendometrial versus placental uterine arteries: Structural, mechanical, and functional differences in late-pregnant rabbits ☆ ☆☆ ★ ★★

OBJECTIVE This study compared late-pregnant radial uterine arteries that supplied the placenta versus the myoendometrium to evaluate differences in active and passive mechanical properties. STUDY DESIGN Pressurized segments of placental versus myoendometrial radial uterine arteries from late-pregnant (day 28 to 30) New Zealand White rabbits (n = 12) were compared in vitro for differences in luminal diameter, wall thickness, distensibility, and intrinsic tone as a function of transmural pressure. RESULTS Both types of arteries responded to increased transmural pressure with active vasoconstriction; however, the amount of tone present in myoendometrial arteries was significantly greater than in placental arteries (percent tone at 75 mm Hg = 39% +/- 3% for myoendometrial versus 31% +/- 2% for placental arteries, p < 0.01). Measurements of unpressurized, fully relaxed arteries revealed that placental arteries were 38% larger in diameter and had thicker walls than myoendometrial arteries did. However, myoendometrial arteries were significantly more distensible at transmural pressures >5 mm Hg. CONCLUSIONS The increased size and diminished tone of placental compared with adjacent myoendometrial arteries would favor increased blood flow to the placenta; differences in size and passive mechanical properties suggest that a localized factor(s) originating from the fetus or placenta contributes to the gestational enlargement of those arteries that perfuse the placenta.

The transplacental potential difference as distinguished from the maternal-fetal potential difference of the guinea-pig.

1. We measured the differences in electrical potential between mother and fetus in the guinea‐pig. The fetus was 33 +/‐ 2 (S.E. of mean) mV negative with respect to the mother. 2. Salts of bromine, sulphate, rubidium, and lithium were injected into pregnant sows and blood samples were obtained from the sows and their fetuses at various times after injection. The transplacental electrical potentials at which each of these ions would be in electrochemical equilibrium across the placental exchange barrier were calculated from the Nernst equation and the concentrations in maternal and fetal plasmas. 3. The differences in transplacental electrical potential calculated from the steady‐state concentrations of these ions in maternal and fetal plasmas were within 1 mV of zero. 4. These observations are consistent with a very small difference in electrical potential across the placental exchange barrier itself, and the generation of a potential difference between mother and fetus at a site other than the exchange barrier.

Electrophysiology of extrafetal membranes

This paper reviews some of the equations that apply to the electrophysiology of the extrafetal membranes, and stresses the limitations that may apply to the use of these equations. A literature review of experimental data on potential differences between the fetus, the extrafetal fluid compartments and the mother leads to the conclusion that the transplacental potential difference is no more than a few millivolts and that, in some species, there is an electrical generator outside the placenta.

Maternal Placental Blood Flow Is Reduced in Proportion to Reduction in Uterine Driving Pressure

ABSTRACT: The relationship between uterine driving pressure and maternal placental blood flow was studied after inflation of an aortic occluder previously placed between the renal and ovarian arteries in 10 conscious pregnant rabbits at 28 ± 1 (mean ± SEM) d of a 30− to 31-d gestation to test the hypothesis that there is autoregulation of maternal placental blood flow. After control measurements, the femoral artery pressure was reduced 22 ± 3% from 83 ± 5 mm Hg and clamped at 65 ± 4 mm Hg (p < 0.001) for 54 ± 4 min by servo control. Carotid artery pressure increased from 86 ± 5 to 98 ± 6 mm Hg (p < 0.01). There was no change in cardiac output (839 ± 78 vs 814 ± 64 mL/min; NS), upper-body flow (651 ± 62 vs 671 ± 55 mL/min; NS), or renal flow (111 ± 14 vs 104 ± 8 mL/min; NS). Blood flow to tissues below the occluder decreased from 188 ± 18 to 143 ± 14 mL/min for the lower body (p < 0.05), 153 ± 15 to 116 ± 11 mL/min for the hindquarters (p < 0.05), and 17.7 ± 1.9 to 12.9 ± 1.4 mL/min for 13 pregnant uterine horns (p < 0.05). Placental flow to live fetuses per horn decreased from 13.0 ± 1.9 to 8.9 ± 1.2 mL/min (p < 0.01), whereas there was no significant change in myoendometrial flow (4.0 ± 0.3 vs 3.5 ± 0.5 mL/min; NS). Uterine oxygen consumption was unchanged (1.15 ± 0.16 vs 1.06 ± 0.13 mL/min; NS). There was no change in the circulating arterial concentration of angioten sin I (2.95 ± 1.07 vs 1.46 ± 0.59 ng · mL−1) or active plasma renin activity (8.83 ± 3.72 vs 10.70 ± 5.56 ng · mL−1 · h−1), but trypsin-activated total plasma renin activity increased from 20.24 ± 2.39 to 27.34 ± 5.33 ng · mL−1 · h−1 (p < 0.05). There was neither a uterine venoarterious difference nor a net uterine release of angiotensin I or active plasma renin activity at any time, but the net uterine release of total plasma renin activity increased from 31.66 ±24.08 to 72.32 ± 19.46 (ng · mL−1 · h−1)-(mL # min−1) (p < 0.05). We conclude that there is no significant autoregulation of placental blood flow in the first hour after reduction in uterine driving pressure in the conscious pregnant rabbit. Uterine hypotension is associated with an increase in arterial pressure above the occluder and with the release of an inactive form of renin from the uterus. The significance of the latter two findings remains conjectural.

Mild hypoxaemia does not alter red blood cell production in fetal sheep.

1. Fetal sheep at 120 days gestation were fitted with upper and lower body arterial and venous catheters in addition to a flow sensor and occluder placed around the aorta below the renal arteries. 2. After 7 days of recovery, the occluder was partially inflated to reduce aortic blood flow to 70% of control. Blood flow reduction was maintained at this level for the remainder of the experiment. 3. Blood samples were taken after 60 min of blood flow reduction and again after 3 or more days of blood flow reduction. 4. There was no change in upper body arterial or venous blood pressure. Lower body arterial blood pressure decreased, as expected. Arterial PO2 decreased while packed cell volume and haemoglobin concentration increased. There was no change in plasma erythropoietin concentrations or plasma renin activity. 5. While both red cell mass and haemoglobin mass increased during the period of the study, the rate of increase was no different from the rate of blood volume increase.

Short-term saralasin blockade of renal hypertension in fetal lambs.

1. In the fetal lamb, suprarenal aortic blood flow reduction is known to lead to an upper body hypertension. The dependency of this hypertension on the renin‐angiotensin system was investigated. 2. Intravenous infusions of saralasin or saline vehicle were begun before suprarenal aortic blood flow reduction and continued for 24 h. 3. In those fetuses receiving saline, upper body arterial blood pressure was significantly elevated both 60 min (P < 0.05) and 24 h (P < 0.05) after blood flow reduction. In those fetuses receiving an infusion of saralasin, upper body arterial blood pressure failed to rise after 60 min of blood flow reduction. However, 24 h later, blood pressure was elevated (P < 0.05), though the increase was not as great as that seen in the saline infused fetuses (P < 0.05). 4. From these results, we conclude that the initial increase in upper body arterial blood pressure seen after suprarenal aortic blood flow reduction is dependent upon the renin‐angiotensin system. However, as early as 1 day later, some other mechanism is responsible for sustaining the hypertension.

Normal Arterial Blood Pressure in the Nephrectomized Fetal Lamb

Arterial blood pressures in 18 lambs who had been nephrectomized 3–24 days before were not significantly different from those of 26 control fetuses or from those of control fetuses in the literature.

Long Term Infusion of Subpressor Doses of Angiotensin II Causes a Delayed Vasoconstriction in the Fetal Placental Circulation of the Sheep |[dagger]| 949

The kidney plays a pivotal role in long term regulation of arterial blood pressure (BP) in the postnatal mammal. Fetal BP may also be controlled by the kidney through a mechanism that alters the rate of net transplacental water acquisition. Prolonged angiotensin (Ang) infusion at a rate that does not change in BP in the short term, causes a slow but substantial rise in BP in both intact and nephrectomized fetal lambs. Angiotensin infusion at the same rate also increases water transfer from mother to conceptus, resulting in polyhydramnios or hydrops fetalis. The present studies were conducted to test the hypothesis that a crucial regulatory role for Ang II in the process of transplacental water acquisition is to cause precapillary vasoconstriction of the placental circulation. This would decrease fetal placental blood flow and the hydrostatic pressure in the fetal placental capillaries, thereby promoting filtration of water towards the fetus. Two intact and 4 bilaterally nephrectomized fetuses at 117-125 d of gestation were instrumented with flow sensor (Transonics), and arterial and venous cathethers. After 2 days of recovery, 5 days of control measurements demonstrated stable BP and umbilical flow. A continuous fetal infusion of Ang II (132 ± μg/d per kg autopsy weight, mean ± SD) was given for 5 days. Ang II rose from 17± 3 pg/ml to 244 ± 51 pg/ml, and did not change over the 5 days. Control BP was 41.5 ± 5 mm Hg. One h after start of infusion BP was 44.5 ± 5 mm Hg, a nonsignificant change. BP then rose at a rate of 3.8 mm Hg per day. One h after stopping Ang II infusion, BP fell by 17.6 ± 3.8 mm Hg, but it remained 8.3 ± 3.0 mm Hg above control, p<0.025. Also, 1 h after starting Ang II infusion, umbilical flow was not significantly decreased. There was no later change in mean flow despite the large increase in BP. After 1 hr of infusion, fetal placental resistance was only 9% greater than control, NS; but after 5 days of Ang II infusion, resistance had almost tripled. This increased resistance was not dependent on circulating Ang II; 1 h after infusion, 69% of the increase in resistance remained. Ang II, continuously infused at a rate that causes a negligible immediate increase in fetal BP and resistance, results in a very slow, but very large increase in fetal placental resistance that is not due to a direct action of circulating Ang II. This result is compatible with a structural alteration of the umbilical vascular bed with long term exposure to a high physiological concentration of Ang II.

Serum Insulin-Like Growth Factor (IGF)-I, IGF-II and IGF Binding Protein -3 Are Not Correlated With Weight of Fetal Rabbits † 907

Serum Insulin-Like Growth Factor (IGF)-I, IGF-II and IGF Binding Protein -3 Are Not Correlated With Weight of Fetal Rabbits † 907