Minimizing the inhaled dose of NO with breath-by-breath delivery of spikes of concentrated gas

Background-Pulmonary vasodilatation with a 100 ppm concentration of NO given as a short burst of a few milliliters at the beginning of each breath (NOmin) was compared with conventionally inhaled NO, in which a full breath of 40 ppm of NO was inhaled (NOCD). Methods and Results-NOmin was studied in 16 patients with severe pulmonary hypertension and in 16 isolated porcine lungs with experimentally induced pulmonary hypertension. We compared volumes of 8 to 38 mt of 100 ppm NO in N-2 injected at the beginning of each breath with conventional inhalation of 40 ppm NO in air. NOCD and NOmin were studied in 4 pigs after inhibition of NO synthase with N-G-nitro-L-arginine methyl ester (1 to 2 mg/kg IV) had raised the pulmonary vascular resistance index (PVRI) from 4.4+/-0.8 to 10.0+/-1.6 mm Hg.L-1.min(-1).kg(-1). A similar comparison was made in 7 isolated porcine lungs after the thromboxane analogue U46619 (10 pmol.L-1.min(-1)) increased the mean PVRI from 4.6+/-0.8 to 12.2+/-1.3 mm Hg.L-1.min(-1).kg(-1). Patients' mean PVRI was reduced from 29.2+/-3.7 to 24.0+/-3.1 with NOmin and 24.5+/-3.3 mm Hg.L-1.min(-1).m(-2) (mean+/-SEM) with NOCD. In isolated porcine lungs, there was the same reduction of PVRI for NOmin and NOCD between 12.7% and 34.8%. Conclusions-A small volume of NO inhaled at the beginning of the breath was equally effective as NOCD but reduced the dose of NO per breath by 40-fold, which ranged from 1.2X10(-8) (0.4 mu g) to 1.6X10(-7) mol/L (4.8 mu g) compared with 5.3X10(-7) (16 mu g) to 1.2X10(-6) mol/L (36 mu g) per breath with NOCD.