Effect of maternal oxytocin on umbilical venous and arterial blood flows during physiological-based cord clamping in preterm lambs

Background Delayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs. Methods and findings At ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (p<0.05) decreased UV (26.2±6.0 to 14.1±4.5 mL.min-1.kg-1) and UA (41.2±6.3 to 20.7 ± 4.0 mL.min-1.kg-1) flows and increased CA pressure and flow (47.1±3.4 to 52.8±3.5 mmHg and 29.4±2.6 to 37.3±3.4 mL.min-1.kg-1). These flows and pressures were partially restored between contractions, but did not return to pre-oxytocin administration levels. Ventilation onset during DCC increased the effects of uterine contractions on UA and UV flows, with retrograde UA flow (away from the placenta) commonly occurring during diastole. Conclusions We found no evidence that amplification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.

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Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord

Children ◽

10.3390/children8050353 ◽

2021 ◽

Vol 8 (5) ◽

pp. 353

Author(s):

Jayasree Nair ◽

Lauren Davidson ◽

Sylvia Gugino ◽

Carmon Koenigsknecht ◽

Justin Helman ◽

...

Keyword(s):

Blood Flow ◽

Perinatal Asphyxia ◽

Arterial Blood Flow ◽

Positive Pressure ◽

Optimal Timing ◽

Delayed Cord Clamping ◽

Arterial Blood ◽

Cord Clamping ◽

Sustained Inflation ◽

Near Term

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.

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Brief asphyxial state following immediate cord clamping accelerates onset of left-to-right shunting across the ductus arteriosus after birth in preterm lambs

Journal of Applied Physiology ◽

10.1152/japplphysiol.00559.2019 ◽

2020 ◽

Vol 128 (2) ◽

pp. 429-439

Author(s):

Joseph J. Smolich ◽

Kelly R. Kenna ◽

Michael M. H. Cheung ◽

Jonathan P. Mynard

Keyword(s):

Blood Flow ◽

Ductus Arteriosus ◽

Left Ventricular ◽

Arterial Blood Flow ◽

Blood Flows ◽

Arterial Blood ◽

Cord Clamping ◽

Umbilical Cord Clamping ◽

Left Ventricular Output ◽

Transition Study

Reversal of shunting across the ductus arteriosus from right-to-left to left-to-right is a characteristic feature of the birth transition. Given that immediate cord clamping (ICC) followed by an asphyxial cord clamp-to-ventilation (CC-V) interval may augment left ventricular (LV) output and central blood flows after birth, we tested the hypothesis that an asphyxial CC-V interval accelerates the onset of postnatal left-to-right ductal shunting. High-fidelity central blood flow signals were obtained in anesthetized preterm lambs (gestation 128 ± 2 days) after ICC followed by a nonasphyxial (∼40 s, n = 9) or asphyxial (∼90 s, n = 9) CC-V interval before mechanical ventilation for 30 min after birth. Left-to-right ductal flow segments were related to aortic isthmus and descending aortic flow profiles to quantify sources of ductal shunting. In the nonasphyxial group, phasic left-to-right ductal shunting was initially minor after birth, but then rose progressively to 437 ± 164 ml/min by 15 min ( P < 0.001). However, in the asphyxial group, this shunting increased from 24 ± 21 to 199 ± 93 ml/min by 15 s after birth ( P < 0.001) and rose further to 471 ± 190 ml/min by 2 min ( P < 0.001). This earlier onset of left-to-right ductal shunting was supported by larger contributions ( P < 0.001) from direct systolic LV flow and retrograde diastolic discharge from an arterial reservoir/windkessel located in the descending aorta and its major branches, and associated with increased pulmonary arterial blood flow having a larger ductal component. These findings suggest that the duration of the CC-V interval after ICC is an important modulator of left-to-right ductal shunting, LV output and pulmonary perfusion at birth. NEW & NOTEWORTHY This birth transition study in preterm lambs demonstrated that a brief (∼90 s) asphyxial interval between umbilical cord clamping and ventilation onset resulted in earlier and greater left-to-right shunting across the ductus arteriosus after birth. This greater shunting 1) resulted from an increased left ventricular output associated with a higher systolic left-to-right ductal flow and increased retrograde diastolic discharge from a lower body arterial reservoir/windkessel, and 2) was accompanied by greater lung perfusion after birth.

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Relationship between portal venous and hepatic arterial blood flows: spectrum of response

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.6.g1010 ◽

1990 ◽

Vol 259 (6) ◽

pp. G1010-G1018 ◽

Cited By ~ 5

Author(s):

T. Kawasaki ◽

F. J. Carmichael ◽

V. Saldivia ◽

L. Roldan ◽

H. Orrego

Keyword(s):

Blood Flow ◽

Arterial Blood Flow ◽

Portal Vein Ligation ◽

Artery Ligation ◽

Blood Flows ◽

Arterial Blood ◽

Group A ◽

Group B ◽

The Relationship ◽

Group D

The relationship between portal tributary blood flow (PBF) and hepatic arterial blood flow (HAF) was studied in awake, unrestrained rats with the radiolabeled microsphere technique. Six distinct patterns of response emerged. In group A (PBF+, HAF 0), ethanol, acetate, glucagon, prostacyclin, and a mixed diet increased PBF without a change in HAF; in group B (PBF+, HAF+), adenosine and histamine increased both PBF and HAF; in group C (PBF 0, HAF+), isoflurane and triiodothyronine did not change PBF but increased HAF; and in group D (PBF-, HAF+), halothane and vasopressin decreased PBF and increased HAF. Acute partial portal vein ligation decreased PBF (56%) and increased HAF (436%). Hypoxia (7.5% O2) decreased PBF (28%) and increased HAF (110%). In group E (PBF+, HAF-), acute hepatic artery ligation increased PBF (35%) and reduced HAF (74%), while in group F (PBF-, HAF-), thyroidectomy reduced PBF and HAF (36 and 47%, respectively). All blood flow responses were accompanied by the expected changes in both portal tributary and hepatic arterial vascular resistances. The data suggest that the portal and hepatic arterial vascular territories have regulatory mechanisms that allow for independent changes.

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Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs

Anesthesiology ◽

10.1097/00000542-200404000-00014 ◽

2004 ◽

Vol 100 (4) ◽

pp. 846-851 ◽

Cited By ~ 18

Author(s):

Paul M. Heerdt ◽

Richard Kang ◽

Andrew The’ ◽

Mir Hashim ◽

Robert J. Mook ◽

...

Keyword(s):

Cardiovascular Effects ◽

Neuromuscular Blocking ◽

Blocking Drug ◽

Histamine Concentration ◽

Duration Of Action ◽

Neuromuscular Blocking Drug ◽

Pulmonary Vasoconstriction ◽

Arterial Blood ◽

Before And After ◽

Plasma Histamine Concentration

Background This investigation determined the cardiopulmonary side effects of a novel nondepolarizing neuromuscular blocking drug with an ultrashort duration of action in anesthetized male beagles. Methods The ED95 for GW280430A was first determined in four animals. These data were then used to guide bolus dosing in multiples of ED95 in six dogs instrumented for hemodynamic measurements as well as inspiratory pressure and pulmonary compliance. Cardiopulmonary data were compared before and after the conclusion of a 60- to 90-min GW280430A infusion and in response to subsequent incremental bolus dosing starting with 3.125 x ED95. An adverse response was regarded as an alteration of 10% or greater in any variable. Arterial blood was obtained for histamine analysis before and 1 min after each dose. Results The ED95 of GW280430A was 0.064 +/- 0.01 mg/kg, and stable neuromuscular blockade was maintained with infusion of 0.012 +/- 0.002 mg.kg(-1).min(-1). With the exception of a late 14% increase in heart rate, there were no cardiopulmonary changes during infusion. Bolus dosing produced no cardiopulmonary change until a decrease in mean arterial pressure was elicited in four of six dogs at 25 x ED95. This response was modest, transient, and associated with a concomitant increase in plasma histamine concentration. There were no accompanying changes indicative of direct myocardial depression, pulmonary vasoconstriction, or bronchospasm. Conclusions These data indicate that GW280430 does not produce demonstrable cardiovascular effects in the anesthetized dog until doses far in excess of the ED95 are administered as a bolus.

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Hemodynamic effects of leukotriene C4 in ovine fetus

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1990.259.6.e851 ◽

1990 ◽

Vol 259 (6) ◽

pp. E851-E855

Author(s):

B. A. Meyer ◽

S. W. Walsh ◽

V. M. Parisi

Keyword(s):

Blood Flow ◽

Vena Cava ◽

Cardiovascular Effects ◽

In Vivo Studies ◽

Leukotriene C4 ◽

Blood Flows ◽

Before And After ◽

Placental Blood ◽

Near Term

Leukotrienes are synthesized during pregnancy and produce cardiovascular effects in adults. We hypothesized that leukotriene C4 would cause vasoconstriction in the fetus and placenta. Eight near-term, unanesthetized ovine fetuses were studied before and after infusion of 10 micrograms leukotriene C4 (LTC4) into the fetal vena cava. Cardiovascular monitoring of maternal and fetal arterial pressures and heart rates was performed. Fetal blood flows were measured by the radioactive-microsphere technique. Sustained elevations in systolic and diastolic blood pressure and decreased fetal heart rate began by 1 min and returned to baseline by 30 min. Arterial pH fell from 7.33 +/- 0.01 to 7.29 +/- 0.01 at 15 min (P less than 0.05) and to 7.29 +/- 0.01 at 30 min (P less than 0.05), with a significant increase in base deficit from 0.7 +/- 0.7 to 3.5 +/- 0.7 at 15 min (P less than 0.05) and to 2.9 +/- 1.0 at 30 min (P less than 0.05). Fetal PO2 and PCO2 were unchanged. Significant decreases in blood flow and resistance were seen in the umbilical placental circulation as well as in fetal skeletal muscle and intestine. Blood flow and resistance were unchanged in the renal and adrenal vascular beds. Fetal administration of LTC4 caused no changes in maternal cardiovascular parameters. These findings represent the first in vivo studies of the effects of a lipoxygenase metabolite on fetal-placental blood flow.

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Delayed cord clamping is associated with improved dynamic cerebral autoregulation and decreased incidence of intraventricular hemorrhage in preterm infants

Journal of Applied Physiology ◽

10.1152/japplphysiol.00049.2019 ◽

2019 ◽

Vol 127 (1) ◽

pp. 103-110 ◽

Cited By ~ 3

Author(s):

Zachary A. Vesoulis ◽

Steve M. Liao ◽

Amit M. Mathur

Keyword(s):

Preterm Infants ◽

Cerebral Autoregulation ◽

Intraventricular Hemorrhage ◽

Risk Index ◽

Delivery Mode ◽

Delayed Cord Clamping ◽

Arterial Blood ◽

Cord Clamping ◽

Significant Difference ◽

Dynamic Cerebral Autoregulation

Delayed cord clamping (DCC) improves neurologic outcomes in preterm infants through a reduction in intraventricular hemorrhage (IVH) incidence. The mechanism behind this neuroprotective effect is not known. Infants born <28 wk gestation were recruited for longitudinal monitoring. All infants underwent 72 h of synchronized near-infrared spectroscopy (NIRS) and mean arterial blood pressure (MABP) recording within 24 h of birth. Infants with DCC were compared with control infants with immediate cord clamping (ICC), controlling for severity of illness [clinical risk index for babies (CRIB-II) score], chorioamnionitis, antenatal steroids, sedation, inotropes, and delivery mode. Autoregulatory dampening was calculated as the transfer function gain coefficient between the MABP and NIRS signals. Forty-five infants were included (DCC; n = 15, paired 2:1 with ICC controls n = 30). ICC and DCC groups were similar including gestational age (25.5 vs. 25.2 wk, P = 0.48), birth weight (852.3 vs. 816.6 g, P = 0.73), percent female (40 vs. 40%, P = 0.75), and dopamine usage (27 vs. 23%, P = 1.00). There was a significant difference in IVH incidence between the DCC and ICC groups (20 vs. 50%, P = 0.04). Mean MABP was not different (35.9 vs. 35.1 mmHg, P = 0.44). Compared with the DCC group, the ICC group had diminished autoregulatory dampening capacity (−12.96 vs. −15.06 dB, P = 0.01), which remained significant when controlling for confounders. Dampening capacity was, in turn, strongly associated with decreased risk of IVH (odds ratio = 0.14, P < 0.01). The results of this pilot study demonstrate that DCC is associated with improved dynamic cerebral autoregulatory function and may be the mechanism behind the decreased incidence of IVH. NEW & NOTEWORTHY The neuroprotective mechanism of delayed cord clamping in premature infants is unclear. Delayed cord clamping was associated with improved cerebral autoregulatory function and a marked decrease in intraventricular hemorrhage (IVH). Improved dynamic cerebral autoregulation may decrease arterial baroreceptor sensitivity, thereby reducing the risk of IVH.

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Pulmonary blood flow, pressure and resistance following tetraethylammonium and aminophylline

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1961.200.2.287 ◽

1961 ◽

Vol 200 (2) ◽

pp. 287-291 ◽

Cited By ~ 10

Author(s):

M. Harasawa ◽

S. Rodbard

Keyword(s):

Blood Flow ◽

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Systemic Blood Pressure ◽

Arterial Blood Flow ◽

Tetraethylammonium Chloride ◽

Blood Flows ◽

Arterial Blood ◽

Pulmonary Arterial ◽

Flow Pressure

The effects of tetraethylammonium chloride (TEAC) and aminophylline on the pulmonary vascular resistance were studied in thoracotomized dogs. Pulmonary arterial blood flow and pressure, and systemic blood pressure were measured simultaneously. Both drugs showed marked hypotensive effects on the systemic vessels. In every instance pulmonary arterial pressures and blood flows were reduced by TEAC given via the pulmonary artery and increased by aminophylline. However, the calculated pulmonary vascular resistance remained essentially unchanged in all experiments. These data challenge the concept that the pulmonary vessels respond to these drugs by active vasodilatation

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