Take a Deep (Nitric Oxide) Breath and Follow the Reverse Translational Research Pathway

Manuel Lobo; Borja Ibanez


Eur Heart J. 2018;39(29):2726-2729. 

In This Article

iNO Dose

Experimental studies have shown that not all iNO concentrations have the same cardioprotective effect. In a mouse model of IRI, NO inhalation at concentrations of 40 and 80 ppm resulted in significantly smaller MI sizes than control therapy, whereas 20 ppm iNO showed no infarct-limiting effect.[17] The NOMI investigators based their selection of an 80 ppm iNO dose on the body of published experimental data[9] and because this dose is the most frequently used high-dose iNO concentration in human pulmonary hypertension studies. However, several reports have shown the clinical safety of iNO concentrations up to 160 ppm.[18] The 80 ppm iNO dose used in the NOMI trial significantly increased plasma cGMP concentrations;[11] however, stronger protective effects might have been expected at higher concentrations. This question could first be addressed in a dose–response study in a large animal model, potentially opening the window to a further RCT with a more appropriate iNO dose.