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Biomedical subjects

L D Longo

Publications and source records attributed to L D Longo.

At least 127 records · Page 7Linked to original sources

Exercise responses in pregnant sheep: oxygen consumption, uterine blood flow, and blood volume.

In an attempt to explore the acute maternal responses to exercise we measured oxygen consumption, uterine blood flow, and blood volume in 13 chronically catheterized pregnant sheep at rest and while exercising on a treadmill. With maximal exercise O2 consumption increased 5.6 times, from a resting value of 5.8 +/- 0.3 (SE) to 32.1 +/- 2.8 ml X min -1 X kg -1, cardiac output increased 2.7 times, from 149 +/- 8 to 404 +/- 32 ml X min -1 X kg -1, and arteriovenous oxygen content difference increased 2.1 times, from 3.9 +/- 0.2 to 8.0 +/- 0.4 ml X dl -1. Total uterine blood flow decreased from a mean resting value of 292 +/- 6 to 222 +/- 19 ml X min -1 X kg fetus -1 near exhaustion during prolonged (40 min) exercise at 70% maximal oxygen consumption. Maternal blood volume decreased 14% (P less than 0.01) from 67.5 +/- 3.7 to 57.8 +/- 3.6 ml X kg -1 during this exercise period, with a 20% decrease in plasma volume without a change in red cell volume. We conclude that uterine blood flow decreases during maternal exercise. However, hemoconcentration helps to maintain a relatively constant oxygen delivery to the uterus.

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Exercise responses in pregnant sheep: blood gases, temperatures, and fetal cardiovascular system.

In an effort to examine the effects of maternal exercise on the fetus we measured maternal and fetal temperatures and blood gases and calculated uterine O2 consumption in response to three different treadmill exercise regimens in 12 chronically catheterized near-term sheep. We also measured fetal catecholamine concentrations, heart rate, blood pressure, cardiac output, blood flow distribution, blood volume, and placental diffusing capacity. Maternal and fetal temperatures increased a mean maximum of 1.5 +/- 0.5 (SE) and 1.3 +/- 0.1 degrees C, respectively. We corrected maternal and fetal blood gas values for the temperatures in vivo. Maternal arterial partial pressure of O2 (PO2), near exhaustion during prolonged (40 min) exercise at 70% maximal O2 consumption, increased 13% to a maximum of 116.7 +/- 4.0 Torr, whereas partial pressure of CO2 (PCO2) decreased by 28% to 27.6 +/- 2.2 Torr. Fetal arterial PO2 decreased 11% to a minimum of 23.2 +/- 1.6 Torr, O2 content by 26% to 4.3 +/- 0.6 ml X dl -1, PCO2 by 8% to 49.6 +/- 3.2 Torr, but pH did not change significantly. Recovery was virtually complete within 20 min. During exercise total uterine O2 consumption was maintained despite the reduction in uterine blood flow because of hemoconcentration and increased O2 extraction. The decrease of 3 Torr in fetal arterial PO2 and 1.5 ml X dl -1 in O2 content did not result in major cardiovascular changes or catecholamine release. These findings suggest that maternal exercise does not represent a major stressful or hypoxic event to the fetus.

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Fetal growth and placental diffusing capacity in guinea pigs following long-term maternal exercise.

To determine the critical level of maternal exercise which produces effects on fetal weight and placental diffusing capacity, we measured the relationship between increasing levels of exercise and its effect on the fetus. Hartley guinea pigs with dated pregnancies were exercised on a treadmill (9.7 m/min at a 6.5% gradient) at one of five exercise levels (0, 15, 30, 45, and 60 min/day). We measured placental diffusing capacity for carbon monoxide (DPCO) fetal body and organ weights, placental weight, and maternal body and heart weights near term (63-64 days). Fetal body weight, kidney weight, and placental weight decreased as a function of increasing exercise level, decreasing 13, 13, and 21% respectively at 60 min/day exercise. DPCO1 decreased from a control value of 2.92 +/- 0.23 to 2.33 +/- 0.10 ml. min-1 torr-1 kg fetal wt in the 15 min/day exercise group, 2.17 +/- 0.08 in the 30 min/day group 2.16 +/- 0.11 in the 45 min/day group, and 2.65 +/- 0.31 in the 60 min/day exercise group. The decrease in placental weight along with the decrease in DPCO per kg of fetal weight suggests that with progressive maternal exercise the fetus is compromised by a smaller than normal placenta with less diffusing capacity.

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Placental exchange area in guinea pigs following long-term maternal exercise: a stereological analysis.

We have used stereological techniques to measure the peripheral labyrinth exchange area of the guinea pig placenta in groups of animals which were exercised 0, 15, 30, 45, or 60 min daily throughout pregnancy. The surface area of the maternal lacunae in the peripheral labyrinth decreased linearly as a function of exercise duration, and the maternal volumes of each exercised group were consistently lower, but not linearly. Placental diffusing capacity for carbon monoxide decreased as a function of exercise duration (r = - 0.88, P less than 0.05). Placental CO diffusing capacity was directly proportional to both maternal surface area of a given volume of peripheral labyrinth (mm2/mm3) (r = 0.43, P less than 0.01), and to the total surface area of the placenta (mm2 . g/mm3) (r = 0.53, P less than 0.001). In addition, diffusing capacity correlated to the total fetal surface area (mm2 . g/mm3), (r = 0.53, P less than 0.001). Average fetal and placental weights did not change significantly in the different exercise groups. Individual fetal weights were proportional to placental diffusing capacity and to both the total maternal and fetal placental exchange area. These results demonstrate for the first time that diffusing capacity of the guinea pig placenta is a function of the surface area of the placenta.

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Patterns of fetal lamb regional cerebral blood flow during and after prolonged hypoxia: studies during the posthypoxic recovery period.

In an effort to determine to what extent cerebral blood flow (CBF) varies in different parts of the brain after prolonged fetal hypoxia, we measured flow to 34 regions. In seven chronically catheterized fetal lambs at 130 to 140 days' gestation, flow was measured by means of radioactive labeled microspheres during a control period, during hypoxia, and at 4, 24, and 48 hours after hypoxia. Control blood flow to cortical, subcortical, and brain stem structures respectively equaled 221, 237 and 275 ml . min-1 . 100 gm-1. After 90 minutes of hypoxia, flows respectively increased 67%, 93%, and 160% to these areas, suggesting preferential shunting of flow to critical brain stem regions. By 4, 24, and 48 hours after hypoxia the regional flows ahd returned to values not significantly different from control values. We conclude that: (1) significant fetal regional cerebral blood flow differences occurred in utero, with brain stem and subcortical flows being greater than flows to other regions of the brain; (2) during prolonged intrauterine hypoxia, total cerebral blood flow increased about 95%, with evidence of preferential shunting to critical brain stem regions; (3) during the posthypoxic recovery period at 4, 24, and 48 hours, flows returned to normal, indicating no evidence of a post-ischemic hypoperfusion syndrome or impairment of the microcirculation.

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Environmental pollution and pregnancy: risks and uncertainties for the fetus and infant.

Numerous environmental contaminants can affect the developing embryo, fetus, or infant. This essay explores such questions as these: What is the importance in mutagenesis and teratogenesis of macroenvironmental pollutants such as the heavy metals, dioxin derivatives, polychlorinated diphenyl compounds, and pesticides? What is the significance of microenvironmental pollutants (or social environmental factors) such as tobacco smoke, alcohol, and pharmacologic agents over which exposed individuals have considerable control? What are some of the ethical and legal implications of these toxins of which clinicians should be aware?

Air Pollutants, Radioactive↗

Clinical and physiologic implications of increased fetal oxygen consumption.

In an effect to determine if placental diffusion reserves exceed fetal oxygen requirements we artificially increased fetal O2 consumption by infusing norepinephrine (NE) or triiodothyronine (T3) into 24 chronically catheterized fetal lambs. After 50 minutes of NE infusion, fetal O2 consumption rose 25%; after 5 days of T3 infusion, it increased 28%. In both instances there was a redistribution of organ blood flows, but placental diffusing capacity and the fetal venous and arterial blood gas values remained essentially unchanged. We concluded that both NE and T3 infusion can result in an increased rate of fetal metabolism with increased oxygen consumption and that the placental reserve for O2 diffusion exceeds normal oxygen requirements.

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Fetal cardiac output measured by four-way thermodilution.

To measure fetal cardiac output by thermodilution, we injected 2.5 ml of iced 5% glucose rapidly into the superior vena cava and recorded areas of temperature-time curves in the brachiocephalic artery (AS) and descending aorta (BS). One minute later we repeated the injection into the inferior vena cava and recorded areas under two curves (AI and BI). Cardiac output was calculated as Qco = H (AS + BI - AI - BS) (ASBI - AIBS), where H is the change in caloric content of the blood. In a mechanical model we found thermal results correlated well with timed collections (r = 0.98) with a slope of 0.995. In 7 acutely prepared fetal lambs, electromagnetic flow probe measurements of total cardiac output (descending aorta + brachiocephalic artery) correlated well (0.90) with thermal measurements. The slope (1.16) was significantly greater than 1.0, reflecting the inclusion of coronary and pulmonary flows in thermal, but not in flow probe, measurements. In 11 acutely and chronically prepared fetal lambs, the correlation between microsphere and thermal measurements was 0.81 with a slope of 1.09, not significantly different from 1.0. Hence, thermodilution gives results comparable to other methods and is convenient, indefinitely repeatable, inexpensive, and nonradioactive.

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Induced fetal hyperthyroidism: cardiac output and oxygen consumption.

In 13 chronically catheterized fetal lambs, we inserted a subcutaneous osmotic minipump that released triiodothyronine (T3) at a rate of 5.9 microgram x h-1. Five days postoperatively, fetal plasma T3 concentration had increased 10-fold from a control value of 18.4 ng x dl-1; reverse T3 and thyroxine had decreased 83 and 61% from control values of 524 ng x dl-1, and 9.5 microgram x dl-1, respectively. Fetal heart rate increased 29% to 210 from 163 beats x min-1, and blood pressure remained constant. Cardiac output measured with radioactive-labeled microspheres increased 22% to 678 +/- 33 from a control value obtained from another group of animals of 554 +/- 16 ml x min-1 x kg-1. Umbilical blood flow also increased 22%, while coronary flow increased 35%, and pulmonary flow increased 90%. In contrast, flow to the thyroid gland decreased 52%. Fetal oxygen consumption increased 28% to 10.5 +/- 0.5 from 8.2 +/- 1.1 ml x min-1 x kg-1. Placental carbon monoxide diffusing capacity and venous and arterial blood gas values remained unchanged. We conclude that 1) sustained fetal T3 infusion is one of the few factors that can increase fetal cardiac output, and may play a role in increasing cardiac output in the newborn infant, 2) T3 infusion results in an increased rate of metabolism with increased oxygen consumption, and 3) placental reserve for oxygen diffusion exceeds normal oxygen requirements.

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Norepinephrine elevation in the fetal lamb: oxygen consumption and cardiac output.

In an effort to determine if placental diffusion reserves exceed fetal O2 requirements, we increased fetal O2 consumption (VO2) by infusing 1.7-11.5 microgram of norepinephrine (NE) . min-1. After 50 min of infusion VO2 rose 25% to 10.2 from 8.2 ml . min-1 . kg fetal wt-1. Placental CO diffusing capacity remained essentially unchanged from control, 0.49 +/- 0.05 (SE) ml . min-1. Torr-1 . kg-1, During the first 5 min of NE infusion fetal arterial blood pressure increased 29%, while heart rate decreased 15%. In addition, coronary, pulmonary, and umbilical blood flow, expressed per kilogram of fetal weight as determined by use of labeled microspheres, increased 50, 162, and 25%, respectively (P less than 0.05), although fetal cardiac output remained constant at 538 +/- 23 (SE) ml . min-1 . kg-1. Finally, we determined the NE-blood pressure dose-response relations for the fetus; Blood pressure increased with doses up to 1 microgram . min-1 . kg-1, but failed to rise further with higher doses. We conclude that 1) fetal VO2 increases with NE infusion 2) the placental reserve for O2 diffusion exceeds normal requirements, and 3) NE infusion is associated with increased blood pressure, bradycardia, and a redistribution of blood flows to the heart, lungs, and placenta despite a constant cardiac output.

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Patterns of fetal lamb regional cerebral blood flow during and after prolonged hypoxia.

In an effort to determine to what extent cerebral blood flow (CBF) varies in different parts of the brain during prolonged fetal hypoxia, we measured flow to 34 regions in 12 chronically catheterized fetal lambs 130 to 140 days gestation. Control values of PO2, PCO2 pH, heart rate, and blood pressure were obtained, and CBF was measured by use of radioactive labeled microspheres during a control period, during (15-, 30-, and 90-min) reduction of maternal inspired O2 concentration (fetal arterial PO2 was maintained at 12 to 15 torr), and 60 min after returning the ewe to room air. control blood flow to cortical, subcortical, and brainstem structures equaled 134, 186, and 254 ml x min-1 x 100 g-1, respectively. During hypoxia, CBF increased 92%, and 60 min after fetal oxygenation was restored, it remained 50% above control values. We noted a similar response in regional CBF to the cortex, subcortex, and brainstem during and after hypoxia. Blood flow to smaller areas within the three major regions were quite homogenous and had a similar pattern of response to hypoxia. We conclude that: (1) significant fetal regional CBF differences occurred in utero with brainstem and subcortical flows being substantially greater than flows to other regions of the brain; (2) during prolonged intrauterine hypoxia, total regional CBF increased 92%; (3) 1 hr after fetal oxygenation was restored, CBF still remained 50% above control values; and finally, (4) there was no significant preferential shunting of regional CBF during prolonged hypoxia in utero.

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Dynamics of maternal-fetal nutrient transfer.

Several mechanisms account for transfer of substances across the placenta, including passive diffusion, facilitated diffusion, active transport, solute drag, and pinocytosis. The rates at which these processes occur and the rates of equilibration of various substances between maternal and fetal circulation vary widely. In general, gases and some ions equilibrate rapidly while large molecules such as proteins exchange slowly. Some nutrients such as amino acids, calcium, iron, and possibly some vitamins are transported against a concentration gradient. This report compares equilibration rates for various nutrients and discusses the use of mathematical modeling to quantitate certain aspects of the processes, and to gain a better understanding of factors determining placental exchange.

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