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

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). 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 mL of 100 ppm NO in N2 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 NG-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%. 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 microg) to 1. 6x10(-7) mol/L (4.8 microg) compared with 5.3x10(-7) (16 microg) to 1.2x10(-6) mol/L (36 microg) per breath with NOCD.