Cardiac two-dimensional imaging and reference values for blood flow velocities in the ovine fetus.

Since the ovine model is the most commonly used for foetal haemodynamic investigation it was felt important 1) to investigate the technical difficulties involved with ultrasound fetal cardiac imaging in this species and 2) to establish normal reference values for ovine cardiac and umbilical blood flow velocity measurements. Both two-dimensional and pulsed Doppler techniques were used for this assessment in 25 unsedated ewes. All morphological features described in human features to identify the ventricular cavities could be found in the ovine fetus with the two-dimensional echocardiogram. Specific differences included a flatten thorax as visualized from the lateral position, the mesocardial position of the heart, and a large left azygos vein behind the left atrium draining blood into a dilated coronary sinus. The mean peak velocities (cm/sec) of the early diastolic wave (E) and the atrial wave (A), along with their calculated ratio, were not statistically different between the two atrio-ventricular valves (E: 30.6 +/- 6.6, 31.2 +/- 6.1; A: 43.0 +/- 8.3, 41.6 +/- 8.0; E/A: .72, .76 for mitral and tricuspid valves respectively). A significant difference was observed between the acceleration times of the blood ejected into the aorta and the pulmonary artery, with the time interval being shorter in the pulmonary artery (Aorta: 0.052 +/- 0.011; Pulmonary artery: 0.037 +/- 0.009 s). A mean pulsatility index of the umbilical artery of 0.89 was recorded. The data recorded in this study should serve as a reference base for further non-invasive studies of the ovine foetal circulatory system using the ultrasound technique.     

Local blood flow velocities in the carotid body of fetal sheep and newborn lambs

Summary Elastically-suspended microelectrodes were used in the vascularly isolated blood-perfused carotid body of fetal and newborn lambs as well as of 6–7-day-old lambs to measure local blood flow velocities by means of hydrogen clearance. Fetal sheep (n=9) carotid bodies elicited mean local blood velocity values between 0.008 and 0.11 cm·s^–1, whereas newborn lamb carotid bodies (n=7) showed values between 0.008 and 0.067 cm·s^–1 at a perfusion pressure range between 30 and 150 mmHg. The 6–7-day-old lamb carotid bodies (n=5) were characterized by values of 0.003 and 0.049 cm·s^–1 over the same perfusion pressure range. Fetal carotid body values were statistically significantly higher than the values of the 6–7-day-old lamb carotid bodies, whereas the newborn carotid body values showed no significant difference to both other groups. The flow velocity/perfusion pressure relationship peaked at perfusion pressure values between 100 and 150 mmHg in all groups with a reduced steepness in the lamb carotid body. It is concluded that local blood flow velocities in the carotid body are similar to that in other organs, and that after birth local blood flow velocities in the carotid body decrease during the first week of life, probably induced by vasoconstriction, changed blood gas values, and/or increasing shunt flow.Abbreviations significance level - D diffusion coefficient - i.v. intravenous - n number of experiments - PCO ₂ carbon dioxide partial pressure - pH negative logarithm of hydrogen ion concentration - PH ₂ hydrogen partial pressure - Po PH₂ with perfusion - P PH₂ without perfusion - PO ₂ oxygen partial pressure - PP perfusion pressure - r radius     

Cardiorespiratory responses to graded reductions of uterine blood flow in the sheep fetus

Pregnant sheep were chronically instrumented with fetal and maternal catheters and an inflatable occluder and electromagnetic flow transducer were placed on the uterine artery. Uterine blood flow was reduced for approximately 15 minutes to 25 percent, 50 percent, or 75 percent of control uterine blood flow. Fetal blood gases, arterial blood pressure, heart rate and regional distribution of blood flow (by radioactive microspheres) were measured. With progressive reduction of uterine blood flow there was an increasing degree of fetal asphyxia, as measured by blood gases and acid base state. At moderate degrees of asphyxia the fetus responded by redistribution of blood flow to certain organs, namely heart, brain, and adrenal gland, thus preserving oxygenation of these organs. During the most severe degree of asphyxia induced by reduction of uterine blood flow to 25 percent of control there is a reduction of fetal blood flow due to generalized vasoconstriction of essentially all organs. We hypothesize that this is due to the inability of the vasodilator mechanisms to sufficiently oppose the vasoconstrictor mechanisms. Also, because the oxygen consumption of the "vital" organs would be decreased this can be described as the stage of decompensation.     

Relationship between fetal electrocorticographic changes and umbilical blood flow in the near-term sheep fetus

Local blood flow was measured with radioactive microspheres in 9 near-term ewes 2 min into successive high and low voltage electrocortical activity states. In an additional 8 animals the umbilical blood flow was measured using an electromagnetic flow-probe on the common umbilical vein. The microsphere data indicated that the blood flow during low and high voltage electrocortical activity was 185 +/- 22 ml/min per kg of fetus (SEM) and 165 +/- 22 ml/min per kg of fetus (P less than 0.01) respectively. Using the electromagnetic flowprobe the average flow during low and high voltage electrocortical activity was 203 +/- 14 ml/min per kg of fetus and 196 +/- 13 ml/min per kg of fetus (P less than 0.05) respectively. We observed that the decrease in the umbilical blood flow preceded the change from low to high voltage electrocortical activity by approximately 1 min. In that time the flow is significantly lower than it was during the preceding measurements taken during the low voltage electrocortical activity periods. This depression was still significantly lower at 3 min into the high voltage electrocortical activity whereas at 5 min into the high voltage state it was elevated to near average values. We conclude that the umbilical blood flow, on the average, is lower in high voltage states than it is in low voltage states and that this change precedes the switch from low to high voltage electrocortical activity.     

Effects of severe reduction in maternal placental blood flow on blood flow distribution in the sheep fetus

To test the hypothesis that fetal lambs are able to maintain oxygen delivery to myocardial, brain and adrenal tissues during reduction in uterine blood flow to 25% of control, we performed experiments on five ewes and their fetuses. A snare occluder was placed around the maternal common hypogastric artery and catheters were placed for measurement of blood pressures, flows, blood gas tensions, pH and oxygen content. After a five day recovery period, control measurements were made. The snare occluder was then closed until the artery was fully occluded. The arterial occlusion caused uteroplacental blood flow to fall to 32 +/- 4% and maternal placental blood flow to fall to 25 +/- 3% of control values. This level of asphyxia was maintained for 19 +/- 3 minutes, when maternal and fetal blood flows were measured again. In response to occlusion, fetal ascending aortic PO2 fell from 21 +/- 2 (SEM) to 13 +/- 2 mmHg (P less than or equal to 0.01), oxygen content from 4.3 +/- 0.3 to 1.4 +/- 0.2 mM (P less than or equal to 0.01) and pH from 7.37 +/- 0.01 to 7.21 +/- 0.05 (P less than or equal to 0.01). PCO2 rose from 48 +/- 1 to 62 +/- 3 mmHg (P less than or equal to 0.01). Fetal arterial blood pressure increased from 51 +/- 3 to 61 +/- 3 mmHg (P less than or equal to 0.001) and heart rate decreased from 172 +/- 10 to 104 +/- 4 beats.min-1 (P less than or equal to 0.01). The heart, brain and adrenals showed vasodilation in response to the asphyxic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic blood flow to the lung after bronchial artery occlusion in anesthetized sheep.

To compare the effectiveness of different embolizing agents in reducing or redistributing bronchial arterial blood flow, we measured systemic blood flow to the right lung and trachea in anesthetized sheep by use of the radioactive microsphere method before and 1 h after occlusion of the bronchoesophageal artery (BEA) as follows: injection of 4 ml ethanol (ETOH) into BEA (group 1, n = 5), injection of approximately 0.5 g polyvinyl alcohol particles (PVA) into BEA (group 2, n = 5), or ligation of BEA (group 3, n = 5). After occlusion, angiography showed complete obstruction of the bronchial vessels. There were no changes in tracheal blood flow in any of the groups. Injection of ETOH produced a 75 +/- 14% (SD) reduction in flow to the middle lobe (P less than 0.02) and a 75 +/- 13% reduction to the caudal lobe (P less than 0.01), whereas injection of PVA produced a smaller reduction in flow to these two lobes (41 +/- 66 and 51 +/- 54%, respectively). After BEA ligation there was a 52 +/- 29% reduction in flow to the middle lobe and a 53 +/- 38% reduction to the caudal lobe (P less than 0.05). This study has significant implications both clinically and experimentally; it illustrates the importance of airway collateral circulation, in that apparently complete radiological obstruction of the BEA does not necessarily mean complete obstruction of systemic blood flow. We also conclude that, in experimental studies in which the role of the bronchial circulation in airway pathophysiology is examined, ETOH is the agent of choice.     

Effects of prolonged reduction in blood flow on submandibular secretory function in anesthetized sheep.

Submandibular vascular and secretory responses to parasympathetic chorda-lingual (C-L) stimulation were investigated in anesthetized sheep before, during, and after an intracarotid (ic) infusion of endothelin-1 (ET-1). Stimulation of the peripheral end of the C-L nerve at 4 and 8 Hz produced a frequency-dependent reduction in submandibular vascular resistance (SVR) associated with a frequency-dependent increase in submandibular blood flow, salivary flow, and Na+, K+, and protein output from the gland. During stimulation at 4 Hz, ic ET-1 significantly increased SVR (P < 0.01), without significantly affecting either the aortic blood pressure or heart rate. Submandibular blood flow (SBF) was reduced by 48 +/- 4% and the flow of saliva by 50 +/- 1%. The effect on blood and salivary flow persisted for at least 30 min after the infusion of ET-1. The reduction in SBF was associated with a diminution in the output of Na+,K+, and protein in the saliva (P < 0.01). These effects persisted for 30 min after the infusion of ET-1 had been discontinued and were linearly related to the flow of plasma throughout.     

Ultrasonic transit-time measurement of blood flow in the umbilical arteries and veins in the bovine fetus during stage II of labor

The vitality of the bovine fetus during parturition depends on an intact umbilical circulation to supply adequate amounts of oxygen and nutrients to the fetus. The goal of the present study was to measure the blood flow in the umbilical vessels during stage II of labor and to determine when blood flow ceases in the umbilical cord. In 20 cows, ultrasonographic transducers were placed on one umbilical vein and one umbilical artery after rupture of the allantochorionic sac, and the blood flow volume per unit time was measured. At the same time, a pressure transducer was placed into the uterus to measure uterine pressure. Parturition was spontaneous in all 20 cows. In 20 live calves born, pH, base excess and lactate concentration were measured in the blood immediately after birth. During the last 90 min before birth the mean total umbilical blood flow (artery and vein combined) was 1.186+/-0.028 L/min. Calves with a blood pH> or =7.2 (n=13) had a higher mean total blood flow than calves with a pH<7.2 (n=7; 1.243+/-0.038 versus 1.095+/-0.038 L/min). In calves with a blood pH<7.2, the mean total blood flow decreased from 1.178+/-0.134 at 20 min before birth to 0.959+/-0.126 L/min at the end of stage II of labor. During this time period, the arterial blood flow did not differ between calves with a blood pH> or =7.2 and<7.2, but venous blood flow decreased significantly in calves with a blood pH<7.2. During uterine contractions, the total umbilical blood flow decreased significantly by 0.22 L/min. The blood flow in the umbilical artery and vein ceased before the calves were completely born.     

Androgen level in the sheep fetus during gestation.

The androgen content of amniotic fluid, plasma, and gonads from 107 fetal lambs was determined by radioimmunoassay in an attempt to understand the ontogeny of gonadal function. Testosterone (T) was too low to be reliably measured in the amniotic fluid from fetuses of either sex. Ovaries were without T activity at any of the stages of gestation studied. Testicular T-5alpha-dihydrotestosterone (T-DHT) concentration steadily decreased from 1.4/ml near term. It is suggested that nongonadal testosterone production increases during fetal life and that T secretion by the fetal testis may contribute steadily less to the plasma pool of T as gestation proceeds.     

Direct injury to the bronchial vasculature in anesthetized sheep.

Injury to the bronchial vasculature may contribute to liquid and solute leakage into the lung during noncardiac pulmonary edema. The purpose of this study was to measure changes in hemodynamics, pulmonary mechanics, extravascular lung water, and lung morphometry after selectively injuring the bronchial vasculature in anesthetized sheep. In two groups of seven sheep, we injected oleic acid (0.1 ml/kg) or normal saline directly into the bronchoesophageal artery. We measured systemic and pulmonary arterial pressures, cardiac output, oxygen saturation, pulmonary resistance and compliance, and lung volumes before and 1 and 4 h after injection. The lungs were removed for measurement of extravascular water, histology, and morphometry. Four hours after injection of oleic acid, cardiac output decreased but pulmonary arterial pressure did not change. In addition, pulmonary resistance increased and dynamic compliance and vital capacity decreased. Extravascular lung water was slightly but significantly greater in the oleic acid group. Histological examination showed interstitial edema and leukocytes in airway walls and sloughing of bronchial epithelium but little or no alveolar edema. Morphometric analysis showed significant thickening of airway walls. We conclude that direct injury to the bronchial vasculature increases lung resistance, decreases dynamic compliance, and increases extravascular lung water by the accumulation of an inflammatory infiltrate in airway walls.     

GABA-mediated inhibition of breathing in the late gestation sheep fetus

The effects of the GABA antagonist picrotoxin, and the GABA agonist muscimol, have been studied in chronically instrumented unanaesthetized fetal sheep of 115-132 days gestation. Picrotoxin (300-400 micrograms/kg intravenous bolus injection) induced a period of stimulated breathing (40-112 min) which was associated with high voltage electrocortical activity, but inhibited by hypoxia. Muscimol (4 mg infused) had the opposite effect and caused a prolonged period of apnoea (85-418 mins) which was followed by a rebound period of increased breathing. These observations suggest that the GABA-ergic system may be involved in the apnoea of high voltage sleep states in the late gestation fetal sheep, but not in the apnoea associated with hypoxaemia in the fetus.