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

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

PLoS ONE ◽

10.1371/journal.pone.0253306 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253306

Author(s):

Fiona J. Stenning ◽

Graeme R. Polglase ◽

Arjan B. te Pas ◽

Kelly J. Crossley ◽

Martin Kluckow ◽

...

Keyword(s):

Cerebral Oxygenation ◽

Cardiovascular Effects ◽

Arterial Blood Flow ◽

Delayed Cord Clamping ◽

Fetal Sheep ◽

Blood Flows ◽

Uterine Contractions ◽

Arterial Blood ◽

Cord Clamping ◽

Before And After

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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Resuscitation with an Intact Cord Enhances Pulmonary Vasodilation and Ventilation with Reduction in Systemic Oxygen Exposure and Oxygen Load in an Asphyxiated Preterm Ovine Model

Children ◽

10.3390/children8040307 ◽

2021 ◽

Vol 8 (4) ◽

pp. 307

Author(s):

Praveen Chandrasekharan ◽

Sylvia Gugino ◽

Justin Helman ◽

Carmon Koenigsknecht ◽

Lori Nielsen ◽

...

Keyword(s):

Blood Flow ◽

Pulmonary Blood Flow ◽

Preterm Neonates ◽

Positive Pressure ◽

Ovine Model ◽

Delayed Cord Clamping ◽

Pulmonary Vasodilation ◽

Cord Clamping ◽

Early Cord Clamping ◽

Initial Oxygen

(1) Background: Optimal initial oxygen (O2) concentration in preterm neonates is controversial. Our objectives were to compare the effect of delayed cord clamping with ventilation (DCCV) to early cord clamping followed by ventilation (ECCV) on O2 exposure, gas exchange, and hemodynamics in an asphyxiated preterm ovine model. (2) Methods: Asphyxiated preterm lambs (127–128 d) with heart rate <90 bpm were randomly assigned to DCCV or ECCV. In DCCV, positive pressure ventilation (PPV) was initiated with 30–60% O2 and titrated based on preductal saturations (SpO2) with an intact cord for 5 min, followed by clamping. In ECCV, the cord was clamped, and PPV was initiated. (3) Results: Fifteen asphyxiated preterm lambs were randomized to DCCV (N = 7) or ECCV (N = 8). The inspired O2 (40 ± 20% vs. 60 ± 20%, p < 0.05) and oxygen load (520 (IQR 414–530) vs. 775 (IQR 623–868), p-0.03) in the DCCV group were significantly lower than ECCV. Arterial oxygenation and carbon dioxide (PaCO2) levels were significantly lower and peak pulmonary blood flow was higher with DCCV. (4) Conclusion: In asphyxiated preterm lambs, resuscitation with an intact cord decreased O2 exposure load improved ventilation with an increase in peak pulmonary blood flow in the first 5 min.

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