Functional adaptations of the coronary microcirculation to anaemia in fetal sheep.
In fetuses, chronic anaemia stimulates cardiac growth; simultaneously, blood flow to the heart muscle itself is increased, and reserve blood flow capacity of the coronary vascular bed is preserved. Here we examined functional adaptations of the capillaries and small blood vessels responsible for delivering oxygen to the anaemic fetal heart muscle using contrast-enhanced echocardiography. We demonstrate that coronary microvascular flux rate doubled in anaemic fetuses compared to control fetuses, both at rest and during maximal flow, suggesting reduced microvascular resistance consistent with capillary widening. Cardiac fractional microvascular blood volume was not greater in anaemic fetuses, suggesting that growth of new microvascular vessels does not contribute to the increased flow per volume of myocardium. These unusual changes in microvascular function during anaemia may indicate novel adaptive strategies in the fetal heart.



Fetal anaemia causes cardiac adaptations that have immediate and life-long repercussions on heart function and health. It is known that resting and maximal coronary conductance both increase during chronic fetal anaemia, but the coronary microvascular changes responsible for the adaptive response are unknown. Until recently, technical limitations have prevented quantifying functional capillary-level adaptations in the in vivo fetal heart. Our objective was to characterise functional microvascular adaptations in chronically anaemic fetal sheep. Chronically instrumented fetuses were randomized to a control group (n = 11) or were made anaemic by isovolumetric haemorrhage (n = 12) for 1 week prior to myocardial contrast echocardiography at 85% of gestation. Anaemia augmented cardiac mass by 23% without changing body weight. In anaemic fetuses, microvascular blood flow per volume of myocardium was twice that of control fetuses at rest, during vasodilatory hyperaemia, and during hyperaemia plus increased aortic pressure. The elevated blood flow was attributable almost entirely to an increase in microvascular blood flux rate whereas microvascular blood volumes were not different between groups at baseline, during hyperaemia, or with hyperaemia plus increased aortic pressure. Increased coronary microvascular flux rate in response to chronic fetal anaemia is consistent with expected reductions in capillary resistance from capillary diameter widening detected in earlier histological studies.
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA. jonkers@ohsu.edu.|Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA. jonkers@ohsu.edu.
Sonnet S
SS
Jonker
Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.|Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA.
Lowell
L
Davis
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.|Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.
Divya
D
Soman
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
J Todd
JT
Belcik
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.|VA Portland Health Care System, Portland, OR, USA.
Brian P
BP
Davidson
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Tamara M
TM
Atkinson
Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.
Adrienne
A
Wilburn
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.|Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.
Samantha
S
Louey
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.|Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.|VA Portland Health Care System, Portland, OR, USA.
George D
GD
Giraud
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Jonathan R
JR
Lindner
D000222:Adaptation, Physiological; D000740:Anemia / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure; D002196:Capillaries / Q000502:physiology / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D005318:Fetal Heart / Q000502:physiology* / Q000503:physiopathology; D006940:Hyperemia / Q000209:etiology* / Q000503:physiopathology; D008833:Microcirculation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D012756:Sheep
coronary circulation; fetal anemia; fetal heart; microvascular imaging