The effect of reducing umbilical blood flow on fetal oxygenation.

The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over th...

https://www.physiology.org/doi/pdf/10.1152/physrev.00005.2018

Evolving and Expanding the Roles of Mitophagy as a Homeostatic and Pathogenic Process.

Changes in left ventricular output from fetal to early neonatal life.

We determined the effects of three components of the birth process on central blood flow patterns in fetal sheep. We instrumented 16 fetal sheep at 133.0 +/- 1.2 days gestation, inserting various intravascular catheters, intubating the trachea, and placing an inflatable balloon around the umbilical cord. After 2-3 days, we determined central blood flow patterns using radionuclide-labeled microspheres under control conditions, during positive pressure ventilation without oxygenation, during ventilation with 100% O2, and after umbilical cord occlusion. The foramen ovale right to left shunt was essentially abolished, decreasing from 102 +/- 48 to 66 +/- 40 ml/min/kg with ventilation, and to only 13 +/- 10 ml/min/kg with oxygenation. The ductus arteriosus right to left shunt decreased progressively, from a control level of 224 +/- 64 to 6 +/- 10 ml/min/kg after umbilical cord occlusion. A ductus arteriosus left to right shunt appeared with oxygenation (41 +/- 26 ml/min/kg) and increased to 65 +/- 43 ml/min/kg after cord occlusion. Left ventricular output increased progressively as a percentage of combined ventricular output (from a control value of 34.8 to 59.5% after cord occlusion), and increased absolutely with ventilation (from 134 +/- 44 to 211 +/- 87 ml/min/kg). However, right ventricular output decreased (from a control value of 258 +/- 75 to 144 +/- 36 ml/min/kg after cord occlusion) so that combined ventricular output did not change. Although the transition from the fetal to neonatal circulatory pattern was accomplished by simulating these three components of the birth process, none is alone responsible for the large increase in combined ventricular output normally seen at birth.

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Effects of Birth-Related Events on Central Blood Flow Patterns

To assess the role of the early postnatal surge in plasma thyroid hormone concentrations on cardiovascular and metabolic adaptations, we measured cardiac output, total oxygen consumption, and plasma triiodothyronine (T3) concentrations in three groups of lambs in the first 6 h after delivery. 15 fetal lambs were prepared at gestational ages of 128-129 d by placing catheters in the brachiocephalic artery, descending aorta, distal inferior vena cava, left atrium, and pulmonary artery so that measurements could be made soon after delivery. They were divided into three groups: Group I comprised five control animals; Group II consisted of five fetuses in which thyroidectomy was performed at surgery at 129 d gestation; and Group III consisted of five animals in which thyroidectomy was performed at term gestation during delivery by caesarian section, prior to severing the umbilical cord. The lambs in Group I exhibited a rapid postnatal rise in T3 concentrations, similar to that described previously, reaching a peak value of about 5 ng/ml. Although the postnatal surge in T3 concentration was arrested in Group II and III animals, Group II had no detectable plasma T3, while the Group III animals had T3 concentrations of about 0.8 ng/ml, which were within the range previously reported for term lamb fetuses. The lambs in group II showed 40-50% lower left ventricular outputs (190 vs. 297 ml/kg per min), systemic blood flows (155 vs. 286 ml/kg per min), and oxygen consumptions (9.8 vs. 20.2 ml/kg per min) as compared with Group I animals over the entire 6-h period. The lambs in Group II also had significantly lower heart rates (131 vs. 192 beats/min) and mean systemic arterial pressures (56 vs. 72 torr). However, there were no significant differences for any of these measurements between the Group III and Group I lambs. The reduction in cardiac output in the Group II animals were reflected in a significantly lower blood flow to the peripheral circulation, but there were no significant differences in blood flow to other organs in the three groups. These studies indicate that plasma thyroid concentrations in the 2-3 wk prior to delivery and not the increase in thyroid hormone concentrations which occur after birth are important for postnatal cardiovascular and metabolic adjustments. We speculate that lack of circulating triiodothyronine in late gestation may affect postnatal cardiovascular adaptation by modifying normal beta adrenergic receptor development.

/pdf/role-of-thyroid-hormone-in-postnatal-circulatory-and-ness4laab9.pdf

Role of Thyroid Hormone in Postnatal Circulatory and Metabolic Adjustments

After birth a decrease in hemoglobin concentration occurs while high metabolic demands are imposed on the infant by the extrauterine environment. Using the resting lamb as a model, we studied the mechanisms that are called into play during this period to maintain oxygen delivery. Measurements were made of oxygen consumption, arterial and mixed venous blood oxygen contents, cardiac output, hemoglobin concentration, percent fetal hemoglobin, 2,3-diphosphoglycerate, and hemoglobin oxygen affinity during the first two postnatal months. There was a rapid decrease in hemoglobin concentration after birth and concomitant decrease in hemoglobin oxygen affinity, changes similar to those described in humans. Cardiac output and oxygen consumption were both very high immediately after birth and declined in parallel, so that arteriovenous oxygen content difference was constant. Thus at rest cardiac output varies as a result of the changing need for oxygen. This relationship is independent of hemoglobin concentration or oxygen affinity within the normal range. If, however, oxygen demands were increased, oxygen delivery might be compromised by a limited ability to increase oxygen extraction during the immediate newborn period or when hemoglobin concentration is lowest.

Oxygen delivery in lambs: cardiovascular and hematologic development.

Limits of 0 2 Delivery during Propanolol-Induced Reduction of Cardiac Output in Lambs after Birth: A Longitudinal Study: 67

/pdf/limits-of-02-delivery-during-propanolol-induced-reduction-of-rpyl2zs61s.pdf

G. Lister

Papers

Oxygen delivery in lambs: cardiovascular and hematologic development.

Limits of 02 Delivery during Propanolol-Induced Reduction of Cardiac Output in Lambs after Birth: A Longitudinal Study: 67