Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E.coli pneumonia and sepsis

Quezado, Zenaide M. N., Charles Natanson, WaheedullahKarzai, Robert L. Danner, Cezar A. Koev, Yvonne Fitz, Donald P. Dolan, Steven Richmond, Steven M. Banks, Laura Wilson, and Peter Q. Eichacker. Cardiopulmonary effects of inhaled nitric oxide in normal dogs andduring E. coli pneumonia and sepsis.J. Appl. Physiol. 84(1): 107-115, 1998.We investigated the effect of inhaled nitric oxide (NO) atincreasing fractional inspired O₂concentrations (FI_O2) onhemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious,spontaneously breathing, tracheotomized 2-yr-old beagles hadintrabronchial inoculation with either 0.75 or 1.5 × 10¹⁰ colony-forming units/kg ofE. coli 0111:B4(infected) or 0.9% saline (noninfected) in one or four pulmonarylobes. We found that neither the severity nor distribution (lobar vs.diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasingFI_O2 (0.08, 0.21, 0.50, and0.85), NO (80 parts/million) progressively increased arterial PO₂ [0.3 ± 0.6, 3 ± 1, 13 ± 4, 10 ± 9 (mean ± SE) Torr, respectively] and decreased the mean arterial-alveolarO₂ gradient (0.5 ± 0.3, 4 ± 2, 8 ± 7, 10 ± 9 Torr, respectively). Incontrast, in noninfected animals, the effect of NO was significantlydifferent and opposite; NO progressively decreased meanPO₂ with increasingFI_O2 (2 ± 1, 5 ± 3, 2 ± 3, and 12 ± 5 Torr, respectively;P < 0.05 compared with infectedanimals) and increased mean arterial-alveolarO₂ gradient (0.3 ± 0.04, 2 ± 2, 1 ± 3, 11 ± 5 Torr; P < 0.05 compared with infected animals). In normal and infectedanimals alike, only at FI_O20.21 did NO significantly lower mean pulmonary artery pressure,pulmonary artery occlusion pressure, and pulmonary vascular resistanceindex (all P < 0.01).However, inhaled NO had no significant effect on increases in meanpulmonay artery pressure associated with bacterial pneumonia. Thus,during bacterial pneumonia, inhaled NO had only modest effects onoxygenation dependent on highFI_O2 and did not affectsepsis-induced pulmonary hypertension. These data do not support a rolefor inhaled NO in bacterial pneumonia. Further studies are necessary todetermine whether, in combination with ventilatory support, NO may havemore pronounced effects.