Inhaled nitric oxide during cardiopulmonary bypass does not protect against lung injury in neonatal swine
Introduction: Inhaled nitric oxide (iNO) administered after cardiopulmonary bypass (CPB) reduces neutrophil margination and edema formation (1). However, when administered during CPB, iNO may accentuate the inflammatory cascade and, therefore, worsen CPB-related lung injury. We hypothesized that the inhalation of nitric oxide during CPB would worsen lung injury in neonatal swine. Methods: Fifteen neonatal swine (2.1-2.8 kg) were randomized to CPB with (n=7) and without (n=8) iNO. In the treatment group, iNO (20ppm) was started before CPB and continued throughout reperfusion. Ninety minutes of low-flow CPB (35mL/lg/min) was performed at 18° C to simulate clinical practice. Cooling and warming occurred at flow rates of 100mLAg/min. After decannulation, the animals were followed for 90 min of reperfusion. Animals were ventilated with 100% oxygen throughout the experiment. Immediately prior to sacrifice, the pulmonary artery was clamped and washed with normal saline. Plasma and bronchial alveolar lavage (BAL) were obtained for determination of reduced glutathione (GSH), oxidized glutathione (GSSH), and s-nitrosoglutathione (GSNO) levels. Lung tissue was quick-frozen for myeloperoxidase (MPO) analysis, formalin fixed for histology, and weighed for wet/dry determination. Results: Although both groups demonstrated increased neutrophils and interstitial thickening on lung histology, there was no difference for the animals that received iNO. There were also no differences between groups in wet/dry ratio, GSH, GSSH, or GSNO. However, MPO was increased in the group that received iNO compared with the control animals (7.0 ± 10.7 vs. 3.7 ± 4.0 ng MPO per mg tissue, p < 0.05 by two-tail t-test assuming unequal variances). Conclusions: Inhaled NO during CPB did not protect against lung injury. In addition, the animals receiving iNO had increased MPO activity indicating a higher level of neutrophil activation. This suggests that iNO may worsen CPB induced injury.
Hubble, CL; Cheifetz, IM; Craig, DM; Meliones, JN; Clark, RH
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