Maternal placental and myometrial blood flow in the pregnant rabbit

1. In anaesthetized rabbits 27-29 days pregnant (term is 31 days) uterine blood flow was measured in an extracorporeal loop between a carotid and the central end of an external iliac artery, the descending aorta and its other branches being tied. Mean flow was 45 +/- 2 ml. min(-1), or 105 +/- 4 ml. min(-1) per kg uterus and contents in thirty-four litters.2. The partition of uterine blood flow to placentas ( approximately 60%), myometrium ( approximately 27%) and vagina ( approximately 13%) as estimated by injection of isotopelabelled microspheres of 35 or 50 mu diameter, was similar in intact rabbits and in those with an extracorporeal loop.3. Maternal blood flow was greater to the placentas of larger foetuses both absolutely and per unit placental weight. Flow to the placentas of dead foetuses was much less than to those of live foetuses, but flow to the adjacent myometrium was not decreased.4. Maternal hypoxaemia (P(a, O2) approximately 40 mm Hg) caused vasoconstriction in the uterine vascular bed after 3-4 min. The distribution of blood flow within the uterus was altered, the placental fraction falling to 32%. This was unaffected by carotid denervation.5. These observations suggest that there are large differences in the physiological control of maternal blood flow to the placenta, myometrium and vagina.     

The partition of uterine blood flow in the pregnant rabbit

1. In pregnant rabbits near term, cardiac output and its distribution were measured by injection of isotope-labelled microspheres into the left ventricle. Hypoxaemia (mean P(a,O2) 35 mm Hg) caused a reduction in placental and renal flows, while myometrial flow was unchanged and coronary and cerebral blood flows increased.2. In the lateral (ovarian) end of the uterine horn foetal and placental weight and absolute maternal placental blood flow were greater than in intermediate or medial positions. Placental flow (per 100 g placental tissue) was most in the most lateral placenta and decreased in the intermediate positions, especially when there were many placentas in the same horn.3. Abortions and runts (more than 2 S.D. below the mean weight for their age) occurred most often in the medial end of the uterine horn, while oversize foetuses (more than 2 S.D. above the mean weight) usually occupied the most lateral position.4. Ovarian blood flow (460 ml./100 g. min) was relatively large (e.g. compared with renal flow, 275 ml./100 g.min).     

Toward ambulatory arteriovenous CO2 removal: initial studies and prototype development

Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger. Initially, reinforced Gore-Tex 6 mm (two) and 8 mm (four) grafts were anastomosed to sheep carotid arteries and jugular veins as a loop in parallel to the cranial circulation to determine blood flow capabilities. Blood flow was 100-150 ml/min with a 14 gauge dialysis needle, and transected 6 mm Gore-Tex grafts achieved 500-900 ml blood flow, whereas transected 8 mm grafts achieved up to 2000 ml/min flow. The polytetrafluoroethylene (PTFE) loops were then connected to our newly developed ultra low resistance pumpless gas exchanger for ambulatory AVCO2R. The average pressure gradient across the prototype Ambulatory-AVCO2R gas exchangers (n = 5) was 2.8 +/- 0.8 mm Hg, and mean CO2 removal was 104.8 +/- 14.0 ml/min, with an average blood flow of 900 ml/min. We conclude that an 8 mm Gore-Tex reinforced graft arteriovenous loop supplies ample blood flow for our new ultra low resistance Ambulatory-AVCO2R to achieve near total CO2 removal.     

Fetomaternal transfer of glucose analogues by sheep placenta

The steady-state permeability of the placenta to radiolabeled 3-O-methyl--D-glucopyranose (3MeG), alpha-methyl-D-glucopyranoside (AMG), and D-xylose was measured in chronically catheterized conscious sheep near term. Fetomaternal flux was calculated by application of Fick's principle to the uterine circulation after injection to the fetus. At a fetal glucose concentration of 10.2 +/- 1.25 mM, the permeability of 3MeG was half the maximal value of 59.5 +/- 11.2 ml/min found by extrapolation to zero glucose concentration. The permeability to 3MeG is considerably greater than is compatible with restricted diffusion, which together with the competitive effect of D-glucose suggests a carrier-mediated transfer mechanism. The permeability to AMG was less than 0.1 ml/min. The specificity pattern of sugar transport from the fetal side of the sheep placenta is different from that reported for gut lumen or kidney tubule in other species. D-Xylose is not metabolically inert after its injection into the fetal lamb.     

Nerve growth factor (NGF) and NGF mRNA change in rat uterus during pregnancy

During pregnancy, the uterus undergoes a profound sympathetic denervation. To explore whether this is associated with changes in neurotrophic factors, we assayed nerve growth factor (NGF) and NGF mRNA in the uterus of non-pregnant and pregnant rats. In the uterine horn, the concentration of NGF and its mRNA decreased during middle and late pregnancy. However, when values were corrected for the increase of uterine weight and total RNA yield during pregnancy, NGF content and mRNA per horn increased during middle and late pregnancy. Similar, but less pronounced, changes were observed in the cervix. By seven days postpartum, both parameters returned to near normal.     

Preferential vascular-based transfer from vagina to the corpus but not to the tubal part of the uterus in postmenopausal women.

BACKGROUND: Vaginal administration of progesterone during infertility treatment has therapeutic advantages over oral administration. However, the reasons for this are poorly defined. To demonstrate a preferential vagina-to-uterus distribution of substances, we investigated cold distribution from vagina to the uterus and rectum. METHOD: In 10 postmenopausal women, thermoprobes were inserted into the uterine cavity and in the rectum at <9 cm or at >9 cm from the anus; temperatures were subsequently measured during 10 min flushing of vagina with cold saline. RESULTS: After 10 min, temperature decreased as follows: uterus, tubal angle: -0.22 +/- 0.07 degrees C, 10 (mean +/- SEM, n); uterus, middle cavity: -1.26 +/- 0.34 degrees C, 9; rectum, <9 cm insertion: -3.69 +/- 0.68 degrees C, 3; rectum, >9 cm insertion: -0.51 +/- 0.19 degrees C, 6. CONCLUSIONS: Despite obviously different distances to the vagina of the uterine and the low rectal probes (<9 cm) the temperature decrease occurred at the same time. Cold transfer from vagina to the uterus and rectum is probably not the result of simple diffusion but of a vascular counter-current transfer. Differential cooling of corpus and tubal angles suggests a different arterial supply; while uterine corpus is supplied from the uterine artery, the tubal angles seem to be mainly supplied from the ovarian artery via the tubal arcade.     

Uterine blood flow: periodic fluctuations of its rate during pregnancy

Daily measurements of the rate of uterine blood flow (ml/min) during the last half of pregnancy of four normal sheep reflected a 17-day cyclic fluctuation (range, 9.5-42 days) superimposed on a linear increase over time. The cyclic increase was not detected in two (of 7) intact ewes or in four pregnant ewes that had been ovariectomized. The cyclic pattern of increase may be related to ovarian activity.     

Relationships between maternal hormones and weight of newborn sheep

Intact and ovariectomized mixed-breed sheep were studied in chronic experiments during the last weeks of pregnancy. Measurements were made of the rate of uterine blood flow (ml/min and ml X min-1 X kg-1, combined weight of fetus, uterus, and placenta) and of arterial and uterine venous concentrations of progestagens, estrone, and estradiol. The birth weight of the lamb was directly related to mean maternal concentrations of estrone and estradiol and to the rate of progestagen release by the uterus and its contents (ng X ml-1 X kg-1), calculated by taking the product of the rate of blood flow and the arteriovenous progestagen difference. Ovariectomy altered the relationship between birth weight and progestagen release. Data suggest that rates of progestagen release both by the fetoplacental unit and by the ovary are proportional to the birth weight of the lamb.     

Uteroplacental blood flow during alkalosis in the sheep.

Uteroplacental blood flow was measured by the radioactive-microsphere technique in eight near-term pregnant ewes during a normal control period and during maternal metabolic alkalosis. All measurements were made on awake, unanesthetized animals. Alkalosis, defined for this study as an arterial pH of 7.60 or greater, was produced by the oral administration of sodium bicarbonate, 3 g/kg body wt. The rise in pH thus produced was unaccompanied by significant changes in systemic arterial blood pressure and cardiac output, while maternal arterial Pco2 rose slightly from control levels. Cotyledonary blood flow declined from a control value of 1,177 ml/min to 1,025 ml/min during alkalosis. This decline of 13 percent in cotyledonary blood flow is significant (P smaller than 0.002). Blood flow to the remaining uterine tissue, or noncotyledonary uterus, did not change with alkalosis, being maintained at approximately 195 ml/min. It is concluded that maternal alkalosis, unaccompained by major changes in Pco2 and systemic arterial pressure, causes a small increase in the resistance of the uteroplacental circulation.     

Permeability of the sheep placenta to unmetabolized polar non-electrolytes.

1. The rate of appearance in uterine venous blood of radioactively labelled, polar, non-electrolytes has been measured following their injection into the foetal circulation in the chronically catheterized sheep near term. Uterine blood flow was measured by an antipyrine technique. 2. Estimates of a placental permeability constant not corrected for area were 61-2 +/- 5-5 ml. min-1 (mean +/- S.E. of mean) for [14C] urea, 1-85 +/- 0-16 for [14C]erythritol and 0-21 +/- 0-03 for [3H]mannitol. Results are also presented for [14C]ethylene glycol, [14C]L-glucose, [14C]mannitol, [51Cr] EDTA and [3H] and [14C]sucrose. 3. In four sheep, permeability measurements for several solutes were made and the results were analysed in terms of restricted diffusion via cylindrical, water-filled pores. Calculation of pore radius was made by a minimum variance method and values ranging from 0-43 to 0-45 nm were obtained. 4. Stability and absence of protein binding of probe molecules was investigated by gel permeation on Sephadex columns.     

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.     

Development of ambulatory arterio-venous carbon dioxide removal (AVCO2R): the downsized gas exchanger prototype for ambulation removes enough CO2 with low blood resistance

We are developing an ultra compact gas exchanger to allow ambulation during arterial-venous CO2 removal (AVCO2R). The ambulatory AVCO2R gas exchanger (135 ml prime volume and 1.3 M2 gas exchange surface area) is made of polymethylpentene hollow fibers. The gas exchanger was attached to sheep carotid artery (12F) and jugular vein (14F) by percutaneous cannulae for 6 hours (n = 5). Device CO2 removal was measured and calculated at a constant blood flow rate of 1 L/min coupled with varying sweep gas from 1 to 15 L/min, and at constant sweep gas flow of 2 L/min coupled with varying blood flow from 0.5 to 1.25 L/min to determine capacity of CO2 removal at Pa CO2 = 40-50 mm Hg. Blood gases, CO2 removal and hemodynamics were recorded at 0, 3, and 6 hours. CO2 removal increased with sweep gas flow rate and with increase of device blood flow. Hemodynamics remained unchanged throughout study. Gas exchanger resistance remained stable at 2.3 +/- 0.53 mm Hg/L/min. CO2 removal with 1 L/min blood flow and 2 L/min sweep gas was 110 +/- 12 then stabilized at 85 +/- 14 mL/min to 6 hours. The compact ambulatory AVCO2R gas exchanger achieves stable, near total CO2 removal for at least 6 hours with a simple arteriovenous shunt.     

Equine uteroplacental metabolism at mid- and late gestation

Uptakes of oxygen, glucose and lactate by the gravid uterus, fetus and uteroplacental tissues were measured in chronically catheterized pregnant ponies and their fetuses at mid- and late gestation (term 335 days). Rates of O2 uptake by the gravid uterus, fetus and uteroplacental tissues were significant at both gestational ages and were 2- to 3-fold higher in late gestation than the mid-gestation values of 3338+/-794, 1352+/-258 and 2035 +/- 602 micromol min(-1), respectively (n = 4). Similarly, there were significant uptakes of glucose by the gravid uterus, fetus and uteroplacental tissues at both mid- and late gestation. However, unlike O2 uptake, glucose uptake by the uterus and uteroplacental tissues did not increase between mid- and late gestation. No significant uptakes or outputs of lactate were observed by the uterus or uteroplacental tissues at either gestational age, although there was a significant umbilical uptake of lactate in late but not mid-gestation. There was no change in the distribution of uterine O2 uptake between the fetus and uteroplacental tissues with increasing gestational age. The uteroplacental tissues accounted for about 50 % of the uterine O2 uptake at both gestational ages. In contrast, the proportion of the uterine glucose uptake used by the uteroplacental tissues decreased from 73.2+/-2.1 % (n = 5) at mid-gestation to 61.1+/-1.9 % (n = 4, P<0.02) in late gestation. The gestational changes in uteroplacental carbohydrate metabolism in the mare differ from those seen in the ewe and may have important consequences for the duration and outcome of pregnancy in the mare.     

体外反搏对犬血流脉动性和血管阻力的影响

为了评价体外反搏是否具有扩张血管和增加血流脉动性的作用 ,制造了犬急性心肌梗塞模型 ,并使犬存活 6周。麻醉后 ,测定左侧颈总动脉血流量和右侧颈总动脉血压。计算反搏前和反搏中脉压差、血压脉动指数、血压的标准差、流量差、流量脉动指数、流量标准差和平均血管阻力。结果显示脉压差、血压脉动指数和血压标准差三个血压脉动性指标分别由反搏前的 30± 9mm Hg、1.2 6± 0 .0 5、8.7± 2 .5 mm Hg升高到反搏中的 4 3± 8mm Hg(P<0 .0 5 )、1.5 4± 0 .13、12 .4± 2 .0 mm Hg (P<0 .0 5 )。流量差、流量脉动指数和流量标准差三个血流脉动性指标分别由反搏前的 317± 4 8ml/ min、2 .85± 0 .2 1、96± 2 1ml/ min升高到反搏中的 4 4 7± 88m l/ min、4 .5 6± 0 .90、131±39m l/ m in,P值均于小 0 .0 5。平均血管阻力由反搏前的 5 78± 72 Wood单位降低到反搏中的 4 76± 85 Wood单位(P<0 .0 5 )。这表明体外反搏可使血管阻力下降 ,血压和血流脉动性增强。     

Carbon dioxide and liver blood flow.

This study was designed to determine blood flow to the liver during hypercapnia and combined hypercapnia-hypoxia with the portal vein and hepatic artery intact except for placement of an electromagnetic flow probe around these vessels. Twenty mongrel dogs weighing 30-45 kg were anesthetized with pentobarbital and flow probes and occluders were surgically implanted. Ten of these dogs were subjected to hypercapnia alone. During inspiration of 6% CO2 in room air, portal vein flow increased from 588 +/- 73 ml/min to 731 +/- 113 ml/min (p less than .05), while hepatic artery flow did not change significantly from its control mean of 221 +/- 38 ml/min. In the remaining dogs, inhalation of 6% O2 resulted in a reduction of portal blood flow within 30 min from 527 +/- 55 ml/min to 381 +/- 41 ml/min (p less than .01). Again, mean hepatic artery flow did not increase significantly above its control of 273 +/- 43 ml/min. Subsequent inhalation of 6% CO2 plus 6% O2 (combined hypercapniahypoxia) for 30 min in these same animals resulted in a significant increase of portal vein blood flow from 514 +/- 46 ml/min to 716 +/- 116 ml/min (p less than .05). Thus, hypercapnia alone increases total liver blood flow, primarily by an increase in portal vein flow. Hypoxia results in a decrease in portal vein flow. The superimposition of hypercapnia on hypoxia restores blood flow to a level close to that found with hypercapnia alone. Hypercapnia in the range of 63 +/- 4 mmHg PCO2 overwhelms the tendency toward a reduction of portal vein blood flow induced by an arterial PO2 of 42 +/- 5 mmHg in the presence of mild hypocapnia (PCO2 : 30.2 +/- 1 mmHg).     

Local versus systemic control of numbers of endometrial T cells during pregnancy in sheep

Pregnancy in sheep is associated with changes in numbers of specific T-lymphocyte populations in the uterine endometrium. These changes probably contribute to evasion by the conceptus of maternal immunological rejection and indicate a possible role for T cells in placental growth, parturition and post-parturient uterine defence against infection. The purpose of the present experiment was to evaluate the relative importance of systemic signals (i.e. those present throughout the uterus or from the circulation, including conceptus hormones secreted into the maternal blood) versus locally acting conceptus signals for regulating changes in numbers of endometrial lymphocytes during pregnancy. The approach taken was to surgically confine pregnancy to one uterine horn and compare differences in lymphocyte numbers between the two uterine horns as well as between both horns of pregnant ewes with those of ovariectomized ewes. As compared with ovariectomized ewes, there was a decline in numbers of CD45R+ lymphocytes within glandular epithelium and an increase in gammadelta T-cell number within the luminal epithelium. These changes occurred in both the pregnant and non-pregnant uterine horns of unilaterally pregnant ewes. Moreover, there were no significant differences in lymphocyte numbers between the two uterine horns of unilaterally pregnant ewes. Expression of CD25 was absent in tissues from both uterine horns. In conclusion, changes in numbers of endometrial lymphocytes during pregnancy, rather than due to locally acting signals of conceptus origin, are the result of hormonal signals of maternal or conceptus origin that either act directly on endometrial lymphocytes or stimulate the uterine endometrium to induce synthesis of regulatory molecules that affect lymphocyte dynamics.     

Pregnancy-induced alterations in the turnover rate of 3H-noradrenaline formed from 3H-tyrosine in guinea-pig uterus.

The rate of noradrenaline (NA) turnover in the non-pregnant and pregnant guinea-pig uterus was determined after the administration of the labelled precursor, tyrosine. Endogenous NA was determined fluorimetrically. In non-pregnant animals the turnover of 3H-NA was slower in the uterine horns (t1/2 = 10 h) and cervix (t1/2 = 9 h) than in the reference organ, heart (t1/2 = 6 h). During pregnancy (60-65 days post coitum) endogenous NA in the heart increased in pace with tissue weight gain; yet, in the uterus there was a drastic reduction, down to zero levels. 3H-NA turnover increased significantly in the cervix, no 3H-NA formation remained in the uterine horn (a situation resembling that following 6-hydroxydopamine induced sympathectomy of non-pregnant animals), and the turnover was unaltered in the heart. The observations confirm the general idea, illustrated by the results in the heart, of a functional adaptation with a constant neuron-target relationship during increased physiological demands. They also confirm that a very peculiar and complex neuron-target relationship develops in the uterus during pregnancy--involving functional and structural denervation of the adrenergic nerve plexus in the uterine horn, whereas an increased activation might explain the changes in neuronal NA and its turnover in the cervix.     

The blood pressure in arteries entering the placentae of guinea pigs,rats, rabbits,and sheep

Summary The blood pressure in arteries entering the placenta-the preplacental pressure-was measured in guinea pigs, rats and rabbits which have hemochorial placentae and in sheep which have an epitheliochorial placenta.It was found that in pregnant guinea pigs, pregnant rats and pregnant rabbits the preplacental blood pressure was 12 (SD=3), 14 (SD=1) and 8 (SD=2) Torr respectively. In pregnant sheep, however, the preplacental blood pressure was 84 (SD=9) Torr.The central arterial pressure was 65 (SD=5), 131 (SD=9), 101 (SD=12) and 107 (SD=21) Torr in pregnant guinea pigs, rats, rabbits and sheep respectively.It was concluded that in the studied animals with a hemochorial placenta the vascular resistance which limits the maternal placental flow lies in the arteries outside the placenta. In opposite of this, in pregnant sheep with the epitheliochorial placenta the main resistance lies inside the placenta. This striking difference may be related to the anatomical differences of the maternal vascular bed in the hemochorial placenta and that in the epitheliochorial planceta.     

小鼠附植前胚在子宫内的迁移能力

目的观察小鼠附植前胚在子宫内的迁移能力。方法将CD-1小鼠受精卵、2-细胞胚、桑椹胚、囊胚、四倍体胚、孤雌活化胚等6种胚共1042枚单侧（右侧）移植CD-1假孕母鼠的输卵管或者子宫,观察移植胚在两侧子宫角内的附植情况。结果共得到45只妊娠鼠,在这45只鼠的右侧子宫角都有不同数目的着床胚,而仅在6只鼠的左侧子宫角发现了6枚着床胚。结论小鼠胚在子宫内的迁移能力非常有限,单侧移植的多个胚很少的机率迁移到另一侧子宫角内着床,不能进行胚均匀分布。     

Interdigestive gastric blood flow: the relation to motor and secretory activities in conscious dogs.

Blood flow in the left gastric artery was measured with an electromagnetic flowmeter in nine conscious beagle dogs. In the fasting state gastric motility and secretion exhibited periodical changes with an average cycle interval of 115.4 +/- 9.7 min. During a quiescent period, when gastric motility and secretion were minimal, the mean blood flow was stable at 33.9 +/- 3.8 ml/min. During the contracting phase each peristaltic contraction was coupled with a rapid fall and rise in blood flow (from 10.5 +/- 1.9 ml/min below to 21.2 +/- 3.8 ml/min above the precontraction levels) in 20-30 s. In addition there was a sustained elevation in blood flow (58.6 +/- 6.4 ml/min at the peak) lasting for 29.1 +/- 2.8 min. The onset of sustained blood flow elevation was preceded by that of motility in 63% of the cycles. In 23% of the cycles blood flow started to rise before the contracting phase began. Pepsin peaks coincided with blood flow peaks in two dogs and preceded the latter in the others. Feeding abolished periodic increases in motility and blood flow. It is concluded that left gastric arterial blood flow is not steady but exhibits dynamic changes in phase with periodic motor and secretory activities of the stomach in fasting conscious dogs.