Functional adaptations of the coronary microcirculation to anaemia in fetal sheep

Abstract

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.

A 1 week IGF-1 infusion decreases arterial insulin concentrations but increases pancreatic insulin content and islet vascularity in fetal sheep

“…At 120 ± 0 days gestational age (term ~147 days), fetal catheters were surgically placed similar to previously described (Jonker et al. ). In brief, to control secretions ewes were given intramuscular atropine (7.5 mg), anesthetized with intravenous ketamine (400 mg) and diazepam (10 mg), and ventilated with oxygen:nitrous oxide (2:0.7) and isoflurane (1.5–2.0%).…”

Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig

“…This may indicate systemic plasticity of the fetal circulation in response to prolonged hypoxia that differs from conditions of hypoxia of shorter durations (i.e., late gestation), which limits the time interval for compensation. An additional compensatory mechanism, such as increased coronary artery perfusion (24), may also be supportive of heart function in the chronically hypoxic fetus.…”

Coronary microvascular dysfunction is associated with degree of anaemia in end‐stage renal disease

“…Anaemia causes a number of maladaptive changes to the cardiovascular system that may predispose to CMD. Chronic anaemia can induce a form of high output cardiac failure, that leads to adverse cardiac remodelling including left ventricular dilatation, volume overload and LVH [ 19 , 20 ]. This is suggested in our cohort, where subjects with CMD had an increased cardiac output, as well as a trend towards increased left ventricular and atrial volumes and markers of myocardial stretch.…”

“…This is suggested in our cohort, where subjects with CMD had an increased cardiac output, as well as a trend towards increased left ventricular and atrial volumes and markers of myocardial stretch. Animal studies in anaemia have shown that in order to maintain adequate myocardial oxygen supply, there is an increase in resting myocardial blood flow compared to non-anaemic controls, predominantly due to capillary widening and reduced blood viscosity [ 20 ]. Thus, in anaemia, the microcirculation operates in a state of supra-normal vasodilation at rest, which may limit its ability to vasodilate further during hyperaemia.…”