Introduction:
Inflammation and immunity are central in the pathogenesis of pulmonary arterial hypertension (PAH), but have not been fully explored in young patients with congenital heart disease and elevated pulmonary artery pressure (PAH-CHD) undergoing surgical repair.
Hypothesis:
Cytokines and related proteins may be differentially expressed in PAH-CHD patients with distinct hemodynamic patterns.
Methods:
Sixteen patients with PAH-CHD were enrolled (Group 1, age 1.13 (0.76-2.48) years, median and interquartile range). Pulmonary artery pressure was 52 (43-66) mmHg, and pulmonary vascular resistance was 5.2 (4.2-8.9) Wood units•m
2
. Patients with pulmonary overcirculation, with no need for cardiac catheterization were included for comparison (Group 2, N=31, age 0.71 (0.43-1.02) years). Pulmonary-to-systemic blood flow ratio (echocardiography) in Group 1 and Group 2 was 1.9 (1.3-2.6) and 2.8 (2.3-3.3) respectively (p=0.008). Thirty-six cytokines were analyzed in serum using a chemiluminescence array.
Results:
In the whole patient group (N=47), MIF chemokine (macrophage migration inhibitory factor) was significantly increased compared to pediatric controls (respective densities 7510±2755 pixels and 5697±2051 pixels, mean±SD, p=0.027). In patients, GROα chemokine (growth-regulated oncogene alpha) was elevated early in life, but decreased exponentially with the age (R
2
=0.21, p=0.001), while interleukin 17E (also called IL-25) increased progressively (R
2
=0.24, p<0.001). MIF was specifically increased in Group 1 compared to Group 2 and controls (respectively, 8494±619 pixels, 6618±477 pixels and 6548±726 pixels, age-adjusted mean±SEM, p=0.037). In contrast, RANTES chemokine (regulated on activation, normal T cell expressed and secreted) was specifically elevated in Group 2 compared to Group 1 and controls (respectively, 74183±3865 pixels, 60130±6455 pixels and 59332±3970 pixels, mean±SEM, p=0.039).
Conclusion:
The data indicate a relationship between cytokine levels and severity of the disease (age, groups), with potential pathophysiological implications. Furthermore, involvement of interleukin 17E and MIF emphasize the role of Th2 immune response already described in PAH.
Effect of dexmedetomidine on pulmonary artery pressure in children with congenital heart disease and pulmonary hypertension
