Greater sympathoadrenal activation with longer preventilation intervals after immediate cord clamping increases hemodynamic lability at birth in preterm lambs.
This study tested the hypothesis that varying degrees of hemodynamic fluctuations seen after birth following immediate cord clamping were related to development of asphyxia with longer cord clamp-to-ventilation intervals, resulting in higher perinatal circulating levels of the catecholamines norepinephrine (NE) and epinephrine (Epi), and thus increased heart rate, blood pressures, and cardiac contractility after birth. Anesthetized preterm fetal lambs were instrumented with1) aortic (AoT) and pulmonary trunk (PT) micromanometers to obtain pressures and the maximal rate of pressure rise (dP/dtmax) as a surrogate measure of ventricular contractility, and2) an AoT catheter to obtain samples for blood gas and catecholamine analyses. After delivery, immediate cord clamping was followed by ventilation ∼40 s (n= 7), ∼60 s (n= 8), ∼90 s (n= 9), or ∼120 s later (n= 8), with frequent blood sampling performed before and after ventilation. AoT O2content fell rapidly after immediate cord clamping (P< 0.001), with an asphyxial state evident at ≥60 s. Plasma NE and Epi levels increased progressively with longer cord clamp-to-ventilation intervals, with an exponential relation between falling AoT O2content and rising catecholamines (R2= 0.64-0.67). Elevated circulating catecholamines persisted for some minutes after ventilation onset, with postbirth surges in heart rate, AoT and PT pressures, and AoT and PT dP/dtmaxlinearly related to logeof catecholamine levels (R2= 0.41-0.54, allP< 0.001). These findings suggest that1) a greater degree of asphyxia-induced sympathoadrenal activation (reflected in elevated circulating catecholamine levels) occurs with longer intervals between immediate cord clamping and subsequent ventilation, and2) this activation is a major determinant of hemodynamic fluctuations evident with birth.
Heart Research, Murdoch Childrens Research Institute, Parkville, Australia; joe.smolich@mcri.edu.au.
Joseph J
JJ
Smolich
Heart Research, Murdoch Childrens Research Institute, Parkville, Australia.
Kelly R
KR
Kenna
Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Prahran, Australia; and.
Murray D
MD
Esler
Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Prahran, Australia; and.|Iverson Health Innovations Research Institute, Swinburne University of Technology, Hawthorn, Australia.
Sarah E
SE
Phillips
Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Prahran, Australia; and.|Iverson Health Innovations Research Institute, Swinburne University of Technology, Hawthorn, Australia.
Gavin W
GW
Lambert
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D062186:Arterial Pressure; D001238:Asphyxia Neonatorum / Q000097:blood / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D002319:Cardiovascular System / Q000294:innervation*; D003250:Constriction; D004837:Epinephrine / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D047928:Premature Birth / Q000097:blood / Q000503:physiopathology*; D012121:Respiration, Artificial; D034561:Sheep, Domestic; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014470:Umbilical Cord / Q000601:surgery*; D015854:Up-Regulation
D015415:Biomarkers; D009638:Norepinephrine; D004837:Epinephrine
birth transition; epinephrine; fetus; newborn; norepinephrine