Myocardial mRNA expression of interleukin-6 and hypoxia inducible factor-1α in neonates with congenital cardiac defects

Background: In neonates with congenital heart disease (CHD), myocardial remodelling involves activation of inflammatory pathways. The role of hypoxemia related pathways is however unknown. This study was therefore designed to investigate myocardial mRNA expression of interleukin (IL)-6 and hypoxia-inducible factor (HIF)-1α in neonates with CHD and analyse its influence on post-operative outcome.

Results: 14 neonates with CHD scheduled for open cardiac surgery were studied. In group 1 (n = 5), pre-operative transcutaneous arterial oxygen saturation (SaO₂) was ≤ 85% and in group 2 (n = 9) > 85%. Expression of IL-6- and HIF-1α-mRNA was studied on right atrial biopsy by RT-PCR and corelated to post-operative (po) outcome. Group 1 patients showed higher mean arterial blood pressure (MAP) and lower glycaemia 4 h po (p = 0.047 and p = 0.021, respectively). In the whole cohort, SaO₂ correlated negatively with MAP (Pearson R: -0.662, p = 0.010). mRNA coding for IL-6 and HIF-1α was detected in the myocardium of all neonates independently of age, gender, or type of CHD. IL6-mRNA expression was not influenced by pre-operative hypoxemia but was associated with higher lactate levels in early po period (Pearson R: 0,611, p = 0,020). HIF-1α-mRNA expression correlated negatively with pre-operative SaO₂ (Pearson R: -0.551, p = 0.04) and with aspartate aminotransferase levels 4 h po (Pearson R: 0.625, p = 0.017).

Conclusion: Our study shows that besides inflammatory pathways, hypoxemia related pathways are activated in the myocardium of neonates with CHD. Myocardial expression of both IL-6-mRNA and HIF-1α-mRNA relates to biological markers of a worse po outcome.