Foetal placental blood flow in the lamb

1. Fifteen sheep foetuses of 1.5-5.2 kg body weight were prepared with indwelling arterial and venous catheters for experimentation one to six days later.2. Unanaesthetized foetuses were found to have mean arterial and central venous blood pressures of 40 +/- 1.5 (S.E. of mean) and 2.0 +/- 0.3 (S.E. of mean) mm Hg respectively, compared to intra-uterine pressure. Intra-uterine pressure was 16 +/- 0.8 (S.E. of mean) mm Hg with respect to atmospheric pressure at mid-uterine level.3. Mean placental blood flow of the foetuses was 199 +/- 20 (S.E. of mean) ml./(min.kg body wt.). Mean cardiac output in eleven of the foetuses was 658 +/- 102 (S.E. of mean) ml./(min.kg).4. Mean foetal and maternal colloid osmotic pressures were 17.5 +/- 0.7 (S.E. of mean) and 20.5 +/- 0.6 (S.E. of mean) mm Hg respectively at 38 degrees C.5. Intravenous infusions into six ewes of 1.8 mole of mannitol and 0.4 mole of NaCl resulted in significant increases in foetal plasma osmolarity, sodium, potassium, and haemoglobin concentrations, without detectable transfer of mannitol to the foetal circulation.6. In the sheep placenta there is osmotic and hydrostatic equilibration of water. As a consequence, there should be an interaction between foetal placental blood flow and foetal water exchange with the maternal circulation. It was concluded that this interaction tends to stabilize foetal placental blood flow.     

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.     

Evidence for altered placental blood flow and vascularity in compromised pregnancies

The placenta is the organ that transports nutrients, respiratory gases, and wastes between the maternal and fetal systems. Consequently, placental blood flow and vascular development are essential components of normal placental function and are critical to fetal growth and development. Normal fetal growth and development are important to ensure optimum health of offspring throughout their subsequent life course. In numerous sheep models of compromised pregnancy, in which fetal or placental growth, or both, are impaired, utero-placental blood flows are reduced. In the models that have been evaluated, placental vascular development also is altered. Recent studies found that treatments designed to increase placental blood flow can 'rescue' fetal growth that was reduced due to low maternal dietary intake. Placental blood flow and vascular development are thus potential therapeutic targets in compromised pregnancies.     

The effect of hyperventilation on maternal placental blood flow in pregnant rabbits

1. In anaesthetized pregnant rabbits near term, cardiac output and its distribution were measured by injection of isotope-labelled microspheres. Hypocapnia (mean arterial P(CO) (2) 18 mm Hg), induced by intermittent positive pressure hyperventilation, caused a 43% reduction in maternal placental blood flow, attributed mainly to vasoconstriction. Myometrial flow was not significantly changed.2. Moderate hypercapnia (mean arterial P(CO) (2) 46 mm Hg) caused no change in placental flow, compared with observations made while breathing air spontaneously (P(CO) (2) 31 mm Hg).3. Intravenous infusions of adrenaline or noradrenaline 1 mug/kg. min caused maternal placental vasoconstriction.4. During the especially warm summer of 1969, there was a mean 46% reduction in maternal placental blood flow in pregnant rabbits near term, breathing room air spontaneously with normal blood gas values and rectal temperatures. This was associated with an increase in the number of runts and dead foetuses.     

Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure

The aim was to measure changes in the oxygen tension within the human placenta associated with onset of the maternal arterial circulation at the end of the first trimester of pregnancy, and the impact on placental tissues. Using a multiparameter probe we established that the oxygen tension rises steeply from <20 mmHg at 8 weeks of gestation to >50 mmHg at 12 weeks. This rise coincides with morphological changes in the uterine arteries that allow free flow of maternal blood into the placenta, and is associated with increases in the mRNA concentrations and activities of the antioxidant enzymes catalase, glutathione peroxidase, and manganese and copper/zinc superoxide dismutase within placental tissues. Between 8 to 9 weeks there is a sharp peak of expression of the inducible form of heat shock protein 70, formation of nitrotyrosine residues, and derangement of the mitochondrial cristae within the syncytiotrophoblast. We conclude that a burst of oxidative stress occurs in the normal placenta as the maternal circulation is established. We speculate that this may serve a physiological role in stimulating normal placental differentiation, but may also be a factor in the pathogenesis of pre-eclampsia and early pregnancy failure if antioxidant defenses are depleted.     

Laser Doppler assessment of human colonic blood flow

We have used laser Doppler flowmetry to assess human colonic blood flow in patients with healthy mucosa and in those with active proctitis. We report a significant correlation between colonic serosal laser Doppler flux readings and serosal tissue oxygen tension (n = 45: r = 0.671: p = 0.001). Mucosal blood flow was measured using the PF309 probe of a Perimed Pf2b set on 12 kHz frequency shift. There was no significant difference throughout the colon in healthy patients. The flow in rectal mucosa was significantly higher in patients with proctocolitis than in normal mucosa.     

Method of measuring human pulmonary capillary blood flow

Pulmonary capillary blood flow Q_c was measured in resting adult subjects by a capacitancel nitrous-oxide-uptake method. A sensitive capacitance respirometer was used to determine changes in pulmonary gas volume. The amount of N₂O absorbed from the lungs V_{N 2}O was obtained by subtracting the slope representing the respiratory gas exchange during air breath holding with a closed glottis from the slope representing the volume change during breath holding following inhalation of a 20–80% mixture of O₂ and N₂O. Alveolar N₂O concentrations before and after breath holding were analyzed by gas chromatography and pulmonary capillary blood flow calculated using Bornstein's modification of the Fick principle. This noninvasive method requires little subject training and minimises psychological influences while allowing Q_c determinations at regular intervals with no discomfort to the patient. 120 Q_c determinations were made on 12 normal subjects. These values were compared to predicted cardiac outputs based upon Fick and dye dilution techniques. The mean pulmonary capillary blood flow per square meter body surface area for the 12 individuals, ages 25–39, weighing 63·5 to 127 Kg, was 3·60±0·38 litres/min/m².     

Laser Doppler assessment of human colonic blood flow

We have used laser Doppler flowmetry to assess human colonic blood flow in patients with healthy mucosa and in those with active proctitis. We report a significant correlation between colonic serosal laser Doppler flux readings and serosal tissue oxygen tension (n = 45: r = 0–671: p = 0–001). Mucosal blood flow was measured using the PF309 probe of a Perimed Pf2b set on 12 kHz frequency shift. There was no significant difference throughout the colon in healthy patients. The flow in rectal mucosa was significantly higher in patients with proctocolitis than in normal mucosa.     

Pregnancy hypertension, placental evidences of low uteroplacental blood flow, and spontaneous premature delivery

This study was undertaken to determine if preeclampsia and low uteroplacental blood flow cause spontaneous preterm births. No non-invasive methods are currently available to accurately measure uteroplacental blood flow, so surrogates that are known to be associated with low uteroplacental flow were used. These are preeclampsia, placental infarcts, abnormally small placental villi, and excessive syncytial knots. Preeclampsia was associated with a frequency of spontaneous preterm births that was 41% greater than expected (P less than .001). Normotensive gestations with placental findings of low uteroplacental blood flow ended preterm 147% more frequently than expected, and when a woman had two such pregnancies in succession, the second had a particularly high frequency of spontaneous preterm delivery (64%). Overall, preeclampsia and placental findings of low uteroplacental blood flow were associated with 26% of the spontaneous preterm deliveries in this study. Preeclampsia and low uteroplacental blood flow may be major causes of preterm birth.     

Fetal cerebral, cardiovascular and metabolic reactions to intermittent occlusion of ovine maternal placental blood flow

In 10 mature, acutely exteriorized fetal sheep cardiovascular, cerebral and metabolic reactions were followed during intermittent occlusions of maternal placenta blood flow. The response was analysed from blood pressure, heart rate, myocardial contractility, combined cardiac output, ST waveform analysis of the fetal ECG, and from the evoked EEG response. The metabolic response was judged from blood gases, pH, lactate and circulating catecholamines. Basal values were within the range seen in the 'chronic' fetal lamb preparation. During moderate asphyxia, achieved by 10 1 min occlusions separated by 2 min periods of free maternal aorta blood flow, cardiovascular performance was increased with a substantial catecholamine surge but minor effects on cerebral and metabolic functions. During the marked asphyxia, achieved by five 2 min occlusions, marked metabolic changes occurred together with abolition of cerebral function. Forty-five minutes after asphyxia, 9/10 of the fetuses had regained cerebral, metabolic and cardiovascular functions.