Lack of evidence for impaired preload or Bezold-Jarisch activation during brief umbilical cord occlusions in fetal sheep

2021 ◽  
Author(s):  
Christopher A. Lear ◽  
Laura Bennet ◽  
Benjamin S. A. Lear ◽  
Jenny A. Westgate ◽  
Alistair Jan Gunn
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Cardiovascular Responses ◽  
Diastolic Filling ◽  
Fetal Sheep ◽  
Blood Flows ◽  
Rapid Fall ◽  
Filling Time ◽  
Cervical Vagotomy ◽  
Femoral Blood

Impaired cardiac preload secondary to umbilical cord occlusion (UCO) has been hypothesized to contribute to intrapartum decelerations, brief falls in fetal heart rate (FHR), through the activation of the Bezold-Jarisch reflex. This cardioprotective reflex increases parasympathetic and inhibits sympathetic outflows triggering hypotension, bradycardia and peripheral vasodilation but its potential to contribute to intrapartum decelerations has never been systematically examined. In this study we performed bilateral cervical vagotomy to remove the afferent arm and the efferent parasympathetic arm of the Bezold-Jarisch reflex. 22 chronically instrumented fetal sheep at 0.85 of gestation received vagotomy (n=7) or sham-vagotomy (control, n=15), followed by three 1-min complete UCOs separated by 4-min reperfusion periods. UCOs in control fetuses were associated with a rapid fall in FHR and reduced femoral blood flow mediated by intense femoral vasoconstriction, leading to hypertension. Vagotomy abolished the rapid fall in FHR (p<0.001), and despite reduced diastolic filling time, increased both carotid (p<0.001) and femoral (p<0.05) blood flow during UCOs, secondary to carotid vasodilation (p<0.01) and delayed femoral vasoconstriction (p<0.05). Finally, vagotomy was associated with an attenuated rise in cortical impedance during UCOs (p<0.05), consistent with improved cerebral substrate supply. In conclusion, increased carotid and femoral blood flows after vagotomy are consistent with increased left and right ventricular output, which is incompatible with the hypothesis that labor-like UCOs impair ventricular filling. Overall, the cardiovascular responses to vagotomy do not support the hypothesis that the Bezold-Jarisch reflex is activated by UCO. The Bezold-Jarisch reflex is therefore mechanistically unable to contribute to intrapartum decelerations.

The ontogeny of hemodynamic responses to prolonged umbilical cord occlusion in fetal sheep

2007 ◽  
Vol 103 (4) ◽  
pp. 1311-1317 ◽  
Author(s):  
Guido Wassink ◽  
Laura Bennet ◽  
Lindsea C. Booth ◽  
Ellen C. Jensen ◽  
Bert Wibbens ◽  
...  
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Rapid Onset ◽  
Hemodynamic Responses ◽  
Fetal Sheep ◽  
Eeg Activity ◽  
Progressive Development ◽  
Arterial Blood ◽  
Femoral Blood Flow ◽  
Femoral Blood

There is evidence that preterm fetuses have blunted chemoreflex-mediated responses to hypoxia. However, the preterm fetus has much lower aerobic requirements than at term, and so moderate hypoxia may not be sufficient to elicit maximal chemoreflex responses; there are only limited quantitative data on the ontogeny of chemoreflex and hemodynamic responses to severe asphyxia. Chronically instrumented fetal sheep at 0.6 ( n = 12), 0.7 ( n = 12), and 0.85 ( n = 8) of gestational age (GA; term = 147 days) were exposed to 30, 25, or 15 min of complete umbilical cord occlusion, respectively. At all ages, occlusion was associated with early onset of bradycardia, profoundly reduced femoral blood flow and conductance, and hypertension. The 0.6-GA fetuses showed a significantly slower and lesser fall in femoral blood flow and conductance compared with the 0.85-GA group, with a correspondingly reduced relative rise in mean arterial blood pressure. As occlusion continued, the initial adaptation was followed by loss of peripheral vasoconstriction and progressive development of hypotension in all groups. The 0.85-GA fetuses showed significantly more sustained reduction in femoral conductance but also more rapid onset of hypotension than either of the younger groups. Electroencephalographic (EEG) activity was suppressed during occlusion in all groups, but the degree of suppression was less at 0.6 GA than at term. In conclusion, the near-midgestation fetus shows attenuated initial (chemoreflex) peripheral vasomotor responses to severe asphyxia compared with more mature fetuses but more sustained hemodynamic adaptation and reduced suppression of EEG activity during continued occlusion of the umbilical cord.

Acute on chronic exposure to endotoxin is associated with enhanced chemoreflex responses in preterm fetal sheep

2013 ◽  
Vol 304 (10) ◽  
pp. R799-R803 ◽  
Author(s):  
Lindsea C. Booth ◽  
Paul P. Drury ◽  
Cameron Muir ◽  
Ellen C. Jensen ◽  
Alistair J. Gunn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Chronic Exposure ◽  
Fetal Sheep ◽  
Hypoxic Injury ◽  
Arterial Blood ◽  
Femoral Blood Flow ◽  
Dose Infusion ◽  
Initial Hypothesis ◽  
Femoral Blood

There is increasing evidence that exposure to infection can sensitize the fetus to subsequent hypoxic injury. However, it is unclear whether this involves compromise of the fetal cardiovascular adaptation to acute asphyxia. Chronically instrumented 103-day-old (0.7 gestational age, term is 147 days) fetal sheep in utero were randomized to receive either gram-negative lipopolysaccharide (LPS) as a continuous low-dose infusion for 120 h plus boluses of 1 μg LPS at 48, 72, and 96 h with asphyxia at 102 h (i.e., 6 h after the final LPS bolus) induced by umbilical cord occlusion for 15 min (LPS treated, n = 8), or the same volume of saline plus occlusion (saline treated, n = 7). Fetuses were killed 5 days after occlusion. LPS was associated with a more rapid fall in fetal heart rate at the onset of occlusion ( P < 0.05) and with minimally lower values during occlusion ( P < 0.05). The LPS-treated fetuses had lower fetal mean arterial blood pressure (BP) and greater carotid artery blood flow (CaBF) before occlusion ( P < 0.05) but showed an increase in BP and fall in CaBF to similar values as saline controls during occlusion. There were no differences between the groups in femoral blood flow before or during occlusion. Contrary to our initial hypothesis, acute on chronic exposure to LPS was associated with more rapid cardiovascular adaptation to umbilical cord occlusion.

Dynamics of cardiovascular responses to repeated partial umbilical cord compression in late-gestation sheep fetus

1997 ◽  
Vol 273 (5) ◽  
pp. H2351-H2360 ◽  
Author(s):  
Dino A. Giussani ◽  
Nobuya Unno ◽  
Susan L. Jenkins ◽  
Richard A. Wentworth ◽  
Jan B. Derks ◽  
...  
Keyword(s):  
Blood Flow ◽  
Umbilical Cord ◽  
Cardiovascular Responses ◽  
Cord Compression ◽  
Secondary Response ◽  
Fetal Sheep ◽  
Compression Phase ◽  
Umbilical Blood ◽  
Group I ◽  
Umbilical Blood Flow

We characterized the detailed hemodynamics of fetal blood pressure, heart rate, common umbilical blood flow, and femoral blood flow responses to partial compression of the umbilical cord and tested the hypothesis that repeated cord compression modulates fetal cardiovascular responses in 10 chronically instrumented fetal sheep at ∼130 days of gestation. In five fetuses ( group I), partial compression of the umbilical cord was induced 12 times, each for 5 min at 15-min intervals. Each cord compression reduced common umbilical blood flow by 50% and produced modest falls in fetal pH (7.33 ± 0 to 7.29 ± 0) and arterial [Formula: see text] (21.1 ± 0.2 to 16.8 ± 0.2 mmHg) and a mild increase in arterial[Formula: see text] (49.9 ± 0.5 to 54.9 ± 0.4 mmHg). Sham experiments were performed in five other fetuses ( group II). Second-by-second analysis of group I fetal cardiovascular data revealed a clear biphasic response to partial cord compression. Phase I (1st min of cord compression) was characterized by a rapid bradycardia and a rapid femoral vasoconstriction (primary response); phase II ( minutes 2–5of cord compression) was characterized by a delayed bradycardia and a return of femoral vascular resistance toward baseline (secondary response). Repeated cord compression abolished the primary, but not the secondary, cardiovascular responses. These results demonstrate that fetal cardiovascular responses to stress may be modified by preexposure to repeated intrauterine challenges.

scholarly journals Does Maturity Affect Cephalic Perfusion and T/QRS Ratio during Prolonged Umbilical Cord Occlusion in Fetal Sheep?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Guido Wassink ◽  
Robert Galinsky ◽  
Paul P. Drury ◽  
Eleanor R. Gunn ◽  
Laura Bennet ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Metabolic Acidosis ◽  
Umbilical Cord ◽  
Fetal Sheep ◽  
Fetal Asphyxia ◽  
Arterial Blood ◽  
Rapid Fall ◽  
Severe Hypotension ◽  
Fetal Compromise

T/QRS ratio monitoring is used to help identify fetal asphyxia. However, immature animals have greater capacity to maintain blood pressure during severe asphyxia, raising the possibility that they may show an attenuated T/QRS increase during asphyxia. Chronically instrumented fetal sheep at 0.6 of gestation (0.6 GA;n= 12), 0.7 GA (n= 12), and 0.8 GA (n= 8) underwent complete umbilical cord occlusion for 30 min, 25 min, or 15 min, respectively. Cord occlusion was associated with progressive metabolic acidosis and initial hypertension followed by severe hypotension, with a more rapid fall in mean arterial blood pressure (MAP) and carotid blood flow (CaBF) with advancing gestation. T/QRS ratio rose after occlusion more rapidly at 0.8 GA than in immature fetuses, to a similar final peak at all ages, followed by a progressive fall that was slower at 0.8 GA than in the immature fetuses. The increase in T/QRS ratio correlated with initial hypertension at 0.8 GA (P<0.05,R2= 0.38), and conversely, its fall correlated closely with falling MAP in all gestational groups (P<0.01,R2= 0.67). In conclusion, elevation of the T/QRS ratio is an index of onset of severe asphyxia in the last third of gestation, but not of fetal compromise.

Changes in blood flow distribution during the perinatal period in fetal sheep and lambs

1992 ◽  
Vol 70 (12) ◽  
pp. 1576-1582 ◽  
Author(s):  
Michelle P. Bendeck ◽  
B. Lowell Langille
Keyword(s):  
Blood Flow ◽  
Adrenal Glands ◽  
Flow Distribution ◽  
Perinatal Period ◽  
Tissue Growth ◽  
Late Gestation ◽  
Blood Flow Distribution ◽  
Total Blood ◽  
Fetal Sheep ◽  
Blood Flows

We have measured total blood flows and blood flows per 100 g tissue to major tissues at 120 and 140 days gestation in fetal sheep and at 3 and 21 days of age in lambs (gestation period = 144 ± 2 days). Between 120 and 140 days gestation, flow per 100 g tissue increased by 74, 150, and 317% in the renal, intestinal, and hepatic arterial beds, but no further significant change in flow was observed at 3 or 21 days postpartum. Blood flows per 100 g to cerebral hemispheres and cerebellar tissues also increased dramatically during late gestation (142 and 121%, respectively), but declined sharply by 3 days postpartum (73 and 75%, respectively). Brain blood flows at 21 days postpartum remained substantially below late gestational levels. Adrenal blood flows per 100 g more than doubled during late gestation, fell by more than half at birth, and only partially recovered by 21 days of age. Blood flows to carcass tissues did not change in late gestation, fell at birth, then partially recovered. Pre- and post-natal increases in brain blood flows were almost entirely attributable to increased perfusion rather than tissue growth, whereas large perinatal increases in flow to the diaphragm paralleled tissue growth. Tissue growth and increased perfusion per 100 g contributed almost equally to increased blood flows to kidneys postnatally, and to adrenal glands and the gastrointestinal tract prenatally.Key words: blood flow, perinatal, birth, fetus, sheep.

scholarly journals Mild chronic hypoxia modifies the fetal sheep neural and cardiovascular responses to repeated umbilical cord occlusion

2007 ◽  
Vol 1176 ◽  
pp. 18-26 ◽  
Author(s):  
Victor M. Pulgar ◽  
Jie Zhang ◽  
G. Angela Massmann ◽  
Jorge P. Figueroa
Keyword(s):  
Umbilical Cord ◽  
Chronic Hypoxia ◽  
Cardiovascular Responses ◽  
Fetal Sheep

Regional adrenal blood flow responses to adrenocorticotropic hormone after chronic embolization of the fetal placental circulation in sheep

1996 ◽  
Vol 148 (3) ◽  
pp. 517-522 ◽  
Author(s):  
A M Carter ◽  
J R G Challis ◽  
P Svendsen
Keyword(s):  
Blood Flow ◽  
Adrenal Cortex ◽  
Adrenocorticotropic Hormone ◽  
Maternal Blood ◽  
Arterial Oxygen ◽  
Fetal Sheep ◽  
Cortical Blood Flow ◽  
Arterial Oxygen Content ◽  
Blood Flows ◽  
Placental Blood

Abstract To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic–pituitary–adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 μm microspheres for 8 days from about day 124 of gestation (term ∼147 days) and sham-embolized controls. Starting before the final embolization (or shamembolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1–24 (0·5 μg/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 ± 15 vs 292 ± 25 ml/min per 100 g tissue; mean ± s.e.; P<0·01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and shamembolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0·05) due to decreased vascular resistance (P<0·01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments. Journal of Endocrinology (1996) 148, 517–522

scholarly journals Mechanisms of neonatal increase in glomerular filtration rate

2008 ◽  
Vol 295 (3) ◽  
pp. R916-R921 ◽  
Author(s):  
Anita J. Turner ◽  
Russell D. Brown ◽  
Mattias Carlström ◽  
Karen J. Gibson ◽  
A. Erik G. Persson
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Umbilical Cord ◽  
Filtration Rate ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Unanesthetized Animals ◽  
Stop Flow

To investigate the mechanisms responsible for the neonatal increase in glomerular filtration rate (GFR), renal function studies (whole kidney and micropuncture) were carried out in anesthesized fetal sheep (133–140 days gestation; term = 150 days) and lambs (12–18 days). Fetuses were delivered and placed in a water bath (39.5°C), keeping the umbilical cord moist and intact. Lambs were studied on a thermostatically controlled heating pad. Animals were prepared for either blood flow studies or micropuncture measurements. Expected differences in blood composition and cardiovascular and renal function were observed between fetuses and lambs, and values obtained for most variables were similar to those measured in chronically catheterized unanesthetized animals. Fetal GFR was much lower than that of lambs (0.20 vs. 0.62 ml·min−1·g kidney−1, P < 0.001). Free-flow, stop-flow, and net filtration pressures (NFP) were lower in the fetuses than the lambs (NFP 20.8 vs. 23.8 mmHg, P < 0.001), as was the calculated ultrafiltration coefficient (0.014 vs. 0.022 ml·min−1·g−1·mmHg−1, P < 0.001). Thus, we conclude that rises in both net filtration pressure and the ultrafiltration coefficient contribute to the large increase in GFR between fetal life and ∼2 wk after birth.

Cardiovascular responses to graded degrees of hypoxaemia in the llama fetus

1995 ◽  
Vol 7 (3) ◽  
pp. 549 ◽  
Author(s):  
AJ Llanos ◽  
RA Riquelme ◽  
FA Moraga ◽  
G Cabello ◽  
JT Parer
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Cerebral Blood Flow ◽  
Cardiovascular Response ◽  
Blood Gases ◽  
Cardiovascular Responses ◽  
Fetal Sheep ◽  
Severe Hypoxaemia ◽  
The Central Nervous System ◽  
Blood Flow Redistribution

The fetal llama exposed to an intense degree of hypoxaemia did not increase cerebral blood flow, but showed a marked peripheral vasoconstriction. The same cardiovascular response is observed in fetal sheep submitted to a extremely severe hypoxaemia, when the initial compensatory vasodilatory mechanisms in brain and heart fail. To investigate whether the fetal llama responses to acute hypoxaemia are adaptive, or whether they are the result of a breakdown of mechanisms of blood flow redistribution that favours the central nervous system, we studied seven fetal llamas (0.6-0.7 of gestation) chronically-catheterized during 1 h of graded and progressive hypoxaemia. Fetal ascending aorta blood gases and fetal cardiac output and its distribution (radiolabelled-microspheres) were measured after 60 min of normoxaemia (B) and at the end of 20 min (H20), 40 min (H40) and 60 min (H60) of hypoxaemia. Data were analysed by ANOVA and Newman-Keuls tests. Each treatment resulted in a lower (P < 0.05) percentage of haemoglobin saturation than hypoxaemia; H40 was lower than H20, and H60 was lower than H20 and H40. No statistical difference was observed among treatments for cardiac output or cerebral blood flow. These results demonstrate that fetal cardiac output and brain blood flow are maintained at all degrees of hypoxaemia, indicating that these cardiovascular responses are an adaptive response in the llama fetus, rather than an index of cardiorespiratory decompensation.

Relationship between the fall in growth hormone secretion at birth and the onset of nonshivering thermogenesis is independent of beta adrenergic stimulation

1995 ◽  
Vol 7 (5) ◽  
pp. 1237 ◽  
Author(s):  
KT Ball ◽  
TR Gunn ◽  
PD Gluckman
Keyword(s):  
Growth Hormone ◽  
Umbilical Cord ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Nonshivering Thermogenesis ◽  
Adrenergic Stimulation ◽  
Fetal Sheep ◽  
Beta Adrenergic ◽  
Rapid Fall ◽  
Plasma Ffa

At the time of birth, many rapid metabolic changes occur including the initiation of nonshivering thermogenesis and a rapid fall in growth hormone concentrations. To evaluate the interaction between these events 5 fetal sheep were studied at 135-144 days' gestation. The fetuses were first cooled 2.22 +/- 0.19 degrees C by circulating cold water through a coil placed around the fetal thorax and then ventilated with oxygen through an exteriorized tracheostomy tube to raise fetal arterial PO2 above 67.5 +/- 14.1 Torr. An hour later the beta adrenergic agonist isoproterenol was infused intravenously for 90 min. The fetuses were then separated from the placenta by occluding the umbilical cord. After 60 min the cooling and then the isoproterenol infusion were stopped and the responses monitored. Basal plasma free fatty acid (FFA 35 +/- 5 microEq L-1) and growth hormone (GH 141 +/- 12 ng mL-1) concentrations were not significantly altered by cooling alone, but oxygenation modestly increased plasma FFA to 237 +/- 55 microEq L-1 (P < 0.01) while GH concentrations fell to 58 +/- 27 ng mL-1 (P < 0.05). Isoproterenol administration did not significantly affect either FFA or GH concentrations. Occlusion of the umbilical cord caused a rapid nearly threefold increase in plasma FFA concentrations to 903 +/- 71 microEq L-1 (P < 0.01) and a fall in the same proportions in GH concentrations to 16 +/- 2 ng mL-1 (P < 0.005). Maximal fetal oxygen consumption was 24.2 +/- 4.4 mL kg-1 min-1. Cessation of cooling induced a significant fall in plasma FFA to 480 +/- 58 microEq L-1 (P < 0.01) and rise in GH concentrations to 46 +/- 5 ng mL-1 (P < 0.01). Following the withdrawal of isoproterenol, the fall in plasma FFA and rise in GH concentrations continued while the fetal oxygen uptake fell to 6.4 +/- 1.7 mliter kg-1 mL-1 (P < 0.01). During the study the variation in plasma GH was inversely correlated with changes in FFA concentrations (R = 0.77, P < 0.001). This study confirms that the major factors initiating nonshivering thermogenesis at birth are: sympathetic stimulation from cutaneous cooling, which was not significantly enhanced by isoproterenol; adequate oxygenation; and removal of placental inhibitor(s). The findings are in agreement with a causal relationship between the initiation of nonshivering thermogenesis and consequent rise in FFA concentrations and the rapid fall in circulating GH concentrations after birth in the lamb, independent of beta adrenergic stimulation.

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