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(Circulation. 1998;98:2429-2432.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

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

Yoshihiko Katayama, MD; Tim W. Higenbottam, MD; George Cremona, MD, PhD; Shinji Akamine, MD; Eric A. G. Demoncheaux, BSc; Adrian P. L. Smith, BSc; ; Thomas E. Siddons, BSc

From the Section of Respiratory Medicine, Division of Medicine, Pharmacology, and Medical Physics, The Medical School, University of Sheffield (UK).

Correspondence to Prof T.W. Higenbottam, Beech Hill Rd, Sheffield S10 2RX, UK. E-mail t.higenbottam{at}sheffield.ac.uk

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 N₂ 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 1.2x10^-8 (0.4 µg) to 1.6x10^-7 mol/L (4.8 µg) compared with 5.3x10^-7 (16 µg) to 1.2x10^-6 mol/L (36 µg) per breath with NO_CD.

Key Words: hypertension, pulmonary • lung • vasodilation

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