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Neural and Endocrine Regulation of Circulation in the Fetus and Newborn

Joan C. Mott, David W. Walker

10.1002/cphy.cp020323

Source: Supplement 8: Handbook of Physiology, The Cardiovascular System, Peripheral Circulation and Organ Blood Flow

Originally published: 1983

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Measurement of Blood Flow
2 Umbilical Circulation
2.1 Umbilical Cord
2.2 Placental and Fetal Membranes
2.3 Vasoactive Agents
3 Regional Circulations
3.1 Brain
3.2 Heart
3.3 Kidneys
3.4 Gastrointestinal Tract and Liver
3.5 Adrenal Gland
3.6 Thyroid Gland
3.7 Brown Adipose Tissue
3.8 Skin, Skeleton, and Skeletal Muscle
4 Pulmonary Circulation
4.1 Nervous Control of Pulmonary Vasculature
4.2 Vasoactive Substances
4.3 Intracranial Pressure
5 Vascular Shunts and Redistribution
5.1 Ductus Venosus
5.2 Foramen Ovale
5.3 Ductus Arteriosus
5.4 Redistribution of Blood Flow
5.5 Growth Retardation
5.6 Cold
6 Vasoactive Substances
6.1 Angiotensin and Aldosterone
6.2 Prostaglandins
6.3 Catecholamines
6.4 Vasopressin
7 Neural Mechanisms
7.1 Baroreceptor Reflexes
7.2 Chemoreceptor Reflexes
7.3 J Receptors
7.4 Central Nervous System
8 Postnatal Changes
8.1 Blood, Plasma, and Interstitial Volumes
8.2 Vascular Development
Figure 1. Figure 1.

Vascular conductance (% control) in umbilical (filled bars) and systemic (open bars) circuits in various experimental circumstances. T3, triiodothyronine.

Data from Table 1
Figure 2. Figure 2.

Pressure‐flow diagrams for the umbilical circulation in fetal lambs of 90 (half‐filled circles), 115 (open circles), and 140 (closed circles) days gestation. Lines, are mean regression lines of all observations at the 3 ages, obtained by aortic compression; points indicate mean femoral arterial pressure of each lamb.

Reproduced with permission from Dawes, G. S.: Feotal and Neonatal Physiology. Copyright © 1968 by Year Book Medical Publishers, Inc., Chicago 94
Figure 3. Figure 3.

Dose‐response relations of 5‐hydroxytryptamine (5‐HT), bradykinin (BK), and angiotensin II (AII) on helical strips of umbilical arteries, chorionic plate arteries, and villous stem arterioles of human placentas. Data represent mean ± SE of responses from 6 experiments in 6 placentas.

From Tulenko 340
Figure 4. Figure 4.

Rise in cerebral blood flow and fall in extracerebral blood flow with increasing partial pressure of CO2 in arterial blood (Paco2), determined by radioactive microspheres introduced into carotid artery of unanesthetized fetal lambs.

From Dunnihoo and Quilligan 117
Figure 5. Figure 5.

Ordinate, tissue blood flow (ml · 100 g−1 · min−1) is greater in the brain stem than in the cortex of unanesthetized fetal lambs. Decrease in mmHg Pao2 (plane perpendicular to paper) and/or increase in mmHg Paco2 (abscissa) causes increase in flow. Numbers near bars are arterial pH.

Data from Ashwal et al. 25, Johnson et al. 185, and Palahniuk et al. 264
Figure 6. Figure 6.

Effect of changes in Pao2 on cerebral blood flow. Dotted line, Paco2 = 45 mmHg for 133Xe‐washout method. [Data from Kjellmer et al. 201.] Other data obtained by microsphere method. Dashed line, pH = 7.37, Paco2 = 45 mmHg. [Data from Jones et al. (Eq. 5, ref. 5,192).] Solid line, pH = 7.30, Paco2 = 42–45 mmHg. [Data from Ashwal et al. 24.] Filled triangles, mean + 1 SE at pH = 7.36−7.26 and Paco2 = 43 mmHg. Open triangles, mean −1 SE at pH = 7.36−7.37 and Paco2 = 41 mmHg.

Data from Cohn et al. 82
Figure 7. Figure 7.

Postnatal development of capillary length and number of branchings in the cerebral cortex of the rat. Maximal increase in branching precedes maximal increase in capillary length.

From Bär and Wolff 27
Figure 8. Figure 8.

Influence of postnatal age on blood flow measured with [14C]antipyrine in various parts of the dog brain. For clarity, individual observations plotted in A only.

From Kennedy et al. 200
Figure 9. Figure 9.

Coronary blood flow in fetal lambs at various mmHg Pao2.

Line data recalculated from Peeters et al. 267; open circles from Cohn et al. 82; open triangles from Ashwal et al. 24
Figure 10. Figure 10.

Summary of changes in coronary vascular resistance engendered by autonomic stimulation. Cephalic ischemia caused a significant rise in resistance in lambs with β‐blockade (upper left); this was abolished by α‐blockade with phentolamine (upper right). A rise in coronary resistance also appeared in lambs with sham adrenalectomy (lower left) but did not occur in those with bilateral adrenalectomy (lower right). N, number of animals. NS, not significant. Vertical brackets, SE.

From Downing et al. 114
Figure 11. Figure 11.

blood flow to the outer and inner cortex of the kidneys of dogs 0.75–70 days old, determined by 133Xe washout.

blood flow to the cortex and medulla expressed as percentage of mean renal blood flow, also determined from 133Xe‐clearance curves.

From Aschinberg et al. 22
Figure 12. Figure 12.

Pressure changes with age in guinea pigs. Changes in mean arterial (A) and glomerular capillary (B) pressures. C: pressure drop along the afferent arteriole, taken as the difference between mean arterial and glomerular pressures. D: effective filtration pressure, calculated as the difference between capillary pressure and the sum of the hydrostatic pressure in the proximal tubule and the plasma colloid osmotic pressure.

From Spitzer and Edelmann 323
Figure 13. Figure 13.

Regional variation in blood flow to intestinal mucosa in piglets (7–20 days old) measured by 86Rb indicator. Lower panel, musculal blood flow to various segments of gastrointestinal tract. Upper panel, change of blood flow to each segment in asphyxiated (filled bars) and resuscitated (open bars) piglets.

From Touloukian et al. 337, by permission of Grune and Stratton, Inc
Figure 14. Figure 14.

Adrenal blood flow in fetal lamb vs. arterial pressure. Filled circles, control measurements. Arrows, changes induced by conditions shown.
Figure 15. Figure 15.

Venous outflow from interscapular and cervical brown fat of anesthetized newborn rabbits 0–6 days old before (C) and after propranolol (P) injection. Black, control; white, during infusion of norepinephrine (NE), epinephrine (E), isoproterenol (ISOP), or glucagon (GC). Propranolol given at 1 mg/kg before catecholamine infusions and at 5 mg/kg before glucagon infusion. All catecholamines infused at 2 μg · kg−1 · min−1 and glucagon at 4 μg · kg−1 · min−1. Vertical lines, SE.

Data from Heim and Hull 162
Figure 16. Figure 16.

Mean pressure‐flow diagrams for the unexpended lungs of 7 fetal lambs (135–143 days gestation) were constructed from mean vascular conductances per kilogram and pressure intercepts for the left lung. Ventilation with N2 and then with air caused a progressive increase in vascular conductance, shown here by the increase in slope and decrease in intercept.

Adapted from Cassin et al. 74
Figure 17. Figure 17.

Mean pressure‐flow diagrams for unexpended lungs of 7 fetal lambs (135–143 days gestation) were constructed from mean vascular conductances per kilogram and pressure intercepts for left lung.

Adapted from Cassin et al. 74
Figure 18. Figure 18.

Left pulmonary arterial pressure‐flow diagrams for unventilated lungs of 7 lambs (126–143 days gestation) under normal conditions (a) and perfused with blood from an asphyxiated twin (c) or from a ventilated twin (d). Dashed line, mean pressure‐flow curve for ventilation of lung with air.

Adapted from Dawes 95
Figure 19. Figure 19.

Pulmonary hypertension in the newborn calf at simulated high altitude: mean pulmonary arterial and aortic pressures averaged for 20 normal calves (control) and 7 calves maintained from birth at a simulated altitude of 11,000 ft or temporarily exposed to 1,000‐ft altitude during early postnatal life.

From Reeves and Leathers 290
Figure 20. Figure 20.

Left pulmonary blood flow and femoral arterial pressure in fetal lamb, 142 days gestation.

stimulation of peripheral end of left vagus (5 ms, 2 mA pulses at 15 Hz) causes vasodilatation.

stimulation of sympathetic nerves to left lung (5 ms, 0.4 mA pulses at 30 Hz) during signal causes vasoconstriction.

From Colebatch et al. 83
Figure 21. Figure 21.

Pressure‐flow diagrams for several groups of normal mature fetal lambs (1, 2, 3) were constructed from mean vascular conductances per kilogram and pressure intercepts for left lung. (Lungs not expansible prior to ∼105 days gestation.) Effect of ventilation with air (5, 6). Increase in conductance after brief expansion of intact lung with 3% O2 and 7% CO2 in N2 (7). Resting conductance of denervated lung (4) and increase after brief expansion (8).

From Colebatch et al. 83
Figure 22. Figure 22.

Curves for pulmonary arterial pressure (PAP) vs. flow () for the fetal goat before (C2), during (C3), and after (C4) infusion of prostaglandin E1 (PGE1, 11.0 μg · kg−1 · min−1).

From Cassin et al. 77
Figure 23. Figure 23.

Effect of ventilation on left pulmonary arterial perfusion pressures (PAP) at constant left pulmonary arterial blood flows () and left atrial pressures (LAP) in fetal goats.

7 untreated fetuses and 8 indomethacin‐treated fetuses, both groups 130 ± 0.5 days gestation.

6 untreated fetuses and 6 indomethacin‐treated fetuses, both 140.5 ± 0.5 days gestation. Vertical ranges, SE.

From Leffler et al. 208
Figure 24. Figure 24.

Pulmonary red blood cell (RBC), plasma, and total blood (RBC + plasma) volumes in fetal and air‐ventilated fetal lambs vs. ventilation time. Values shown at time 0 refer to unventilated fetal lungs of 4 lambs. In lambs ventilated with air after draining lungs of liquid (2 ventilated for 5 min and 2 for 20 min), RBC, plasma, and total blood volumes were similar and significantly greater than fetal volumes.

From Walker et al. 351
Figure 25. Figure 25.

Changes in organ blood flows during acute hypoxemia calculated from data of Table 17. Open bars, microspheres introduced into arterial system; closed bars, microspheres introduced into umbilical vein.

Data from Cohn et al. 82 and Reuss and Rudolph 292
Figure 26. Figure 26.

Organ blood flow as measured from microsphere distribution in newborn rabbits and lambs under thermoneutral conditions and during cold exposure.

Data from Alexander et al. 12 and Jarai 182
Figure 27. Figure 27.

Plasma concentrations of norepinephrine and epinephrine in unanesthetized fetal lambs after 60 min of hypoxia (9% O2 + 3% CO2 in N2 administered to ewe). Vertical lines, SD.

From Jones 187
Figure 28. Figure 28.

Norepinephrine and epinephrine content (μg) of adrenals and paraganglia of 6 fetal rabbits at 29 days gestation. Vertical lines, SE.

From Brundin 61
Figure 29. Figure 29.

Serial vascular changes during the first 9 mo of life in unanesthetized dogs of weights shown at the bottom of diagram. Ordinates from above downwards: heart rate (HR), beats · min−1; cardiac output (CO), liters · min−1 · kg−1; mean arterial pressure (MAP), kPa; total peripheral resistance (TPR), kPa · liters−1. min−1; plasma volume (PV), liters · kg−1; central venous pressure (CVP), kPa.

From Magrini 227
Figure 30. Figure 30.

Circulation changes with postnatal change in body weight in lightly anesthetized rabbits and cats. Arterial pressure in mmHg, hemoglobin content in g/100 ml blood, blood volume in ml/kg.

From Mott 247
Figure 31. Figure 31.

Changes with age in percent distribution of blood volume in organs of piglets.

From Lindekamp et al. 212


Figure 1.

Vascular conductance (% control) in umbilical (filled bars) and systemic (open bars) circuits in various experimental circumstances. T3, triiodothyronine.

Data from Table 1


Figure 2.

Pressure‐flow diagrams for the umbilical circulation in fetal lambs of 90 (half‐filled circles), 115 (open circles), and 140 (closed circles) days gestation. Lines, are mean regression lines of all observations at the 3 ages, obtained by aortic compression; points indicate mean femoral arterial pressure of each lamb.

Reproduced with permission from Dawes, G. S.: Feotal and Neonatal Physiology. Copyright © 1968 by Year Book Medical Publishers, Inc., Chicago 94


Figure 3.

Dose‐response relations of 5‐hydroxytryptamine (5‐HT), bradykinin (BK), and angiotensin II (AII) on helical strips of umbilical arteries, chorionic plate arteries, and villous stem arterioles of human placentas. Data represent mean ± SE of responses from 6 experiments in 6 placentas.

From Tulenko 340


Figure 4.

Rise in cerebral blood flow and fall in extracerebral blood flow with increasing partial pressure of CO2 in arterial blood (Paco2), determined by radioactive microspheres introduced into carotid artery of unanesthetized fetal lambs.

From Dunnihoo and Quilligan 117


Figure 5.

Ordinate, tissue blood flow (ml · 100 g−1 · min−1) is greater in the brain stem than in the cortex of unanesthetized fetal lambs. Decrease in mmHg Pao2 (plane perpendicular to paper) and/or increase in mmHg Paco2 (abscissa) causes increase in flow. Numbers near bars are arterial pH.

Data from Ashwal et al. 25, Johnson et al. 185, and Palahniuk et al. 264


Figure 6.

Effect of changes in Pao2 on cerebral blood flow. Dotted line, Paco2 = 45 mmHg for 133Xe‐washout method. [Data from Kjellmer et al. 201.] Other data obtained by microsphere method. Dashed line, pH = 7.37, Paco2 = 45 mmHg. [Data from Jones et al. (Eq. 5, ref. 5,192).] Solid line, pH = 7.30, Paco2 = 42–45 mmHg. [Data from Ashwal et al. 24.] Filled triangles, mean + 1 SE at pH = 7.36−7.26 and Paco2 = 43 mmHg. Open triangles, mean −1 SE at pH = 7.36−7.37 and Paco2 = 41 mmHg.

Data from Cohn et al. 82


Figure 7.

Postnatal development of capillary length and number of branchings in the cerebral cortex of the rat. Maximal increase in branching precedes maximal increase in capillary length.

From Bär and Wolff 27


Figure 8.

Influence of postnatal age on blood flow measured with [14C]antipyrine in various parts of the dog brain. For clarity, individual observations plotted in A only.

From Kennedy et al. 200


Figure 9.

Coronary blood flow in fetal lambs at various mmHg Pao2.

Line data recalculated from Peeters et al. 267; open circles from Cohn et al. 82; open triangles from Ashwal et al. 24


Figure 10.

Summary of changes in coronary vascular resistance engendered by autonomic stimulation. Cephalic ischemia caused a significant rise in resistance in lambs with β‐blockade (upper left); this was abolished by α‐blockade with phentolamine (upper right). A rise in coronary resistance also appeared in lambs with sham adrenalectomy (lower left) but did not occur in those with bilateral adrenalectomy (lower right). N, number of animals. NS, not significant. Vertical brackets, SE.

From Downing et al. 114


Figure 11.

blood flow to the outer and inner cortex of the kidneys of dogs 0.75–70 days old, determined by 133Xe washout.

blood flow to the cortex and medulla expressed as percentage of mean renal blood flow, also determined from 133Xe‐clearance curves.

From Aschinberg et al. 22


Figure 12.

Pressure changes with age in guinea pigs. Changes in mean arterial (A) and glomerular capillary (B) pressures. C: pressure drop along the afferent arteriole, taken as the difference between mean arterial and glomerular pressures. D: effective filtration pressure, calculated as the difference between capillary pressure and the sum of the hydrostatic pressure in the proximal tubule and the plasma colloid osmotic pressure.

From Spitzer and Edelmann 323


Figure 13.

Regional variation in blood flow to intestinal mucosa in piglets (7–20 days old) measured by 86Rb indicator. Lower panel, musculal blood flow to various segments of gastrointestinal tract. Upper panel, change of blood flow to each segment in asphyxiated (filled bars) and resuscitated (open bars) piglets.

From Touloukian et al. 337, by permission of Grune and Stratton, Inc


Figure 14.

Adrenal blood flow in fetal lamb vs. arterial pressure. Filled circles, control measurements. Arrows, changes induced by conditions shown.



Figure 15.

Venous outflow from interscapular and cervical brown fat of anesthetized newborn rabbits 0–6 days old before (C) and after propranolol (P) injection. Black, control; white, during infusion of norepinephrine (NE), epinephrine (E), isoproterenol (ISOP), or glucagon (GC). Propranolol given at 1 mg/kg before catecholamine infusions and at 5 mg/kg before glucagon infusion. All catecholamines infused at 2 μg · kg−1 · min−1 and glucagon at 4 μg · kg−1 · min−1. Vertical lines, SE.

Data from Heim and Hull 162


Figure 16.

Mean pressure‐flow diagrams for the unexpended lungs of 7 fetal lambs (135–143 days gestation) were constructed from mean vascular conductances per kilogram and pressure intercepts for the left lung. Ventilation with N2 and then with air caused a progressive increase in vascular conductance, shown here by the increase in slope and decrease in intercept.

Adapted from Cassin et al. 74


Figure 17.

Mean pressure‐flow diagrams for unexpended lungs of 7 fetal lambs (135–143 days gestation) were constructed from mean vascular conductances per kilogram and pressure intercepts for left lung.

Adapted from Cassin et al. 74


Figure 18.

Left pulmonary arterial pressure‐flow diagrams for unventilated lungs of 7 lambs (126–143 days gestation) under normal conditions (a) and perfused with blood from an asphyxiated twin (c) or from a ventilated twin (d). Dashed line, mean pressure‐flow curve for ventilation of lung with air.

Adapted from Dawes 95


Figure 19.

Pulmonary hypertension in the newborn calf at simulated high altitude: mean pulmonary arterial and aortic pressures averaged for 20 normal calves (control) and 7 calves maintained from birth at a simulated altitude of 11,000 ft or temporarily exposed to 1,000‐ft altitude during early postnatal life.

From Reeves and Leathers 290


Figure 20.

Left pulmonary blood flow and femoral arterial pressure in fetal lamb, 142 days gestation.

stimulation of peripheral end of left vagus (5 ms, 2 mA pulses at 15 Hz) causes vasodilatation.

stimulation of sympathetic nerves to left lung (5 ms, 0.4 mA pulses at 30 Hz) during signal causes vasoconstriction.

From Colebatch et al. 83


Figure 21.

Pressure‐flow diagrams for several groups of normal mature fetal lambs (1, 2, 3) were constructed from mean vascular conductances per kilogram and pressure intercepts for left lung. (Lungs not expansible prior to ∼105 days gestation.) Effect of ventilation with air (5, 6). Increase in conductance after brief expansion of intact lung with 3% O2 and 7% CO2 in N2 (7). Resting conductance of denervated lung (4) and increase after brief expansion (8).

From Colebatch et al. 83


Figure 22.

Curves for pulmonary arterial pressure (PAP) vs. flow () for the fetal goat before (C2), during (C3), and after (C4) infusion of prostaglandin E1 (PGE1, 11.0 μg · kg−1 · min−1).

From Cassin et al. 77


Figure 23.

Effect of ventilation on left pulmonary arterial perfusion pressures (PAP) at constant left pulmonary arterial blood flows () and left atrial pressures (LAP) in fetal goats.

7 untreated fetuses and 8 indomethacin‐treated fetuses, both groups 130 ± 0.5 days gestation.

6 untreated fetuses and 6 indomethacin‐treated fetuses, both 140.5 ± 0.5 days gestation. Vertical ranges, SE.

From Leffler et al. 208


Figure 24.

Pulmonary red blood cell (RBC), plasma, and total blood (RBC + plasma) volumes in fetal and air‐ventilated fetal lambs vs. ventilation time. Values shown at time 0 refer to unventilated fetal lungs of 4 lambs. In lambs ventilated with air after draining lungs of liquid (2 ventilated for 5 min and 2 for 20 min), RBC, plasma, and total blood volumes were similar and significantly greater than fetal volumes.

From Walker et al. 351


Figure 25.

Changes in organ blood flows during acute hypoxemia calculated from data of Table 17. Open bars, microspheres introduced into arterial system; closed bars, microspheres introduced into umbilical vein.

Data from Cohn et al. 82 and Reuss and Rudolph 292


Figure 26.

Organ blood flow as measured from microsphere distribution in newborn rabbits and lambs under thermoneutral conditions and during cold exposure.

Data from Alexander et al. 12 and Jarai 182


Figure 27.

Plasma concentrations of norepinephrine and epinephrine in unanesthetized fetal lambs after 60 min of hypoxia (9% O2 + 3% CO2 in N2 administered to ewe). Vertical lines, SD.

From Jones 187


Figure 28.

Norepinephrine and epinephrine content (μg) of adrenals and paraganglia of 6 fetal rabbits at 29 days gestation. Vertical lines, SE.

From Brundin 61


Figure 29.

Serial vascular changes during the first 9 mo of life in unanesthetized dogs of weights shown at the bottom of diagram. Ordinates from above downwards: heart rate (HR), beats · min−1; cardiac output (CO), liters · min−1 · kg−1; mean arterial pressure (MAP), kPa; total peripheral resistance (TPR), kPa · liters−1. min−1; plasma volume (PV), liters · kg−1; central venous pressure (CVP), kPa.

From Magrini 227


Figure 30.

Circulation changes with postnatal change in body weight in lightly anesthetized rabbits and cats. Arterial pressure in mmHg, hemoglobin content in g/100 ml blood, blood volume in ml/kg.

From Mott 247


Figure 31.

Changes with age in percent distribution of blood volume in organs of piglets.

From Lindekamp et al. 212
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Article Title: Neural and Endocrine Regulation of Circulation in the Fetus and Newborn
 

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Joan C. Mott, David W. Walker. Neural and Endocrine Regulation of Circulation in the Fetus and Newborn. Compr Physiol 2011, Supplement 8: Handbook of Physiology, The Cardiovascular System, Peripheral Circulation and Organ Blood Flow: 837-883. First published in print 1983. doi: 10.1002/cphy.cp020323