Is the increase in NO lung transfer due to free plasmatic hemoglobin in pulmonary arterial hypertension

Inhaled NO is rapidly fixed to Hb to form MetHb in red cells (RC). Free Hb in plasma (fHb) has a reactivity 400 times greater than RCHb. NO lung transfer (DLNO) is used to test the alveolo-capillary membrane. Patients with fHb should increase their NO lung transfer. High DLNO/DLCO ratios have been reported in patients with pulmonary arterial hypertension (PAHT)(Van der Lee et al, 2006) and the presence of fHb in patients with PAHT has been reported (Fox et al 2012). The aim was to analyze the relationship between DLNO and fHb in a small cohort of patients with PAHT. 17 patients followed up for PAHT had fHb analysis on venous blood. DLNO and DLCO measurements were performed on the same day (Medisoft Be). The ratio DLNO/DLCO was taken as an index for analysis. The upper limit of the normal for this ratio is 5.5 (Aguilaniu et al 2005). 10/17 patients had a ratio DLNO/DLCO above 5.5. 10/17 had fHb concentration above the normal value, however the correlation between both parameters was weak and not significant (r=0.27). The correlation was better(r=-0.40) with haptoglobin concentration which is known to scavenge fHb. High fHb were correlated with low PaO2 and high arterial pulmonary pressures (systolic, mean and diastolic). These results suggest that the relationship between fHb and DLNO is not straight. If all haptoglobin molecules are comsumed, fHb might infiltrate tissues including lung parenchyma which would biased the correlation of DLNO/DLCO and fHb. This view is supported by the better correlation with haptoglobin concentration. These results suggest also that the observed microlysis is caused by mechanical RC damages due to high arterial pulmonary pressures.