Evaluating the combination of bovine lactoferrin and Bifidobacterium breve M‐16V in human milk for prevention of infection and inflammation in preterm neonates

of Medical Resarch, the Hudson Institute of Medical Research/ Monash University and Monash Newborn Background: Preterm infants frequently suffer from cardiovascular compromise due to tissue hypoxia, leading to hypotension and/or low systemic blood flow. Many preterm infants respond inadequately to inotropic treatments using adrenergic agonists such as dobutamine or dopamine. This may be due to altered quantity or type of cardiac adrenoceptor expression due to tissue hypoxia-ischaemia (HI), or prolonged exposure to adrenergic agonists. We measured the effects of severe HI and dobutamine/dopamine treatment on cardiac adrenoreceptors in preterm fetal sheep. Method: Fetal sheep (93-95d) exposed to sham surgery or severe HI induced by umbilical cord occlusion, received intravenous dobutamine (DB) or saline (sal) for 72 hrs (HI + DB, HI + sal, Sham + DB, Sham + sal, n = 6 in each group). Fetal hearts were then collected for beta-adrenoceptor binding site assay, and mRNA expression of beta1, beta2, alpha1A, alpha2A and alpha2B-adrenoceptor. Groups were compared using two-way ANOVA. The HI groups were also compared with fetal sheep exposed to HI and dopamine (HI + DA, n = 6) using one-way ANOVA (Significant P-value < 0.05). Results: HI + sal had higher beta-adrenoceptor density (fmol/ mg) than all other groups in all 4 heart chambers. DB significantly decreased beta1 and beta2 mRNA in the left ventricle (LV). Post-hoc analyses showed that HI + DB had lower beta1and beta2-mRNA than HI + sal. HI + DA had lower alpha1AmRNA than HI + sal in LV. Conclusions: HI increases cardiac beta-adrenoceptor density. But dobutamine down-regulates the beta1& beta2-mRNA and dopamine down-regulates alpha1A-mRNA expression. Prolonged exposure to adrenergic agonists downregulates cardiac adrenoceptors in the preterm heart exposed to HI, and may underpin the frequent failure of inotropic therapy in preterm infants.