Minimizing the Inhaled Dose of NO With Breath-by-Breath Delivery of Spikes of Concentrated Gas

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Abstract
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 (NO min ) was compared with conventionally inhaled NO, in which a full breath of 40 ppm of NO was inhaled (NO CD ). Methods and Results —NO min 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 N 2 injected at the beginning of each breath with conventional inhalation of 40 ppm NO in air. NO CD and NO min 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 NO min and 24.5±3.3 mm Hg · L −1 · min −1 · m −2 (mean±SEM) with NO CD . In isolated porcine lungs, there was the same reduction of PVRI for NO min and NO CD between 12.7% and 34.8%. Conclusions —A small volume of NO inhaled at the beginning of the breath was equally effective as NO CD but reduced the dose of NO per breath by 40-fold, which ranged from 1.2×10 −8 (0.4 μg) to 1.6×10 −7 mol/L (4.8 μg) compared with 5.3×10 −7 (16 μg) to 1.2×10 −6 mol/L (36 μg) per breath with NO CD .