Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock

Patrick J. Offner, Hiroshi Ogura, Bryan S. Jordan, Basil A. Pruitt, William G. Cioffi

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: Nitric oxide synthase (NOS) inhibition has been shown to potentiate lipopolysaccharide (LPS) associated pulmonary hypertension, which may women right ventricular (RV) dysfunction and decrease cardiac output during sepsis. This study evaluates whether inhaled nitric oxide can ameliorate the adverse cardiopulmonary effects of NOS inhibition during endotoxemia. Methods: After an infusion of Escherichia coli LPS (200 μg/kg), animals were resuscitated with saline (1 mL/kg/min) and observed for 3 hours while mechanically ventilated (FIO2, 0.6; V(T), 12 mL/kg; positive end- expiratory pressure, 5 cm H2O). The LPS group (n = 6) received no additional treatment. The N-nitro-L-arginine methyl ester (NAME) group (n = 5) receive L-NAME, a NOS inhibitor, 50 μg/kg/min for the last 2 hours. The NO+NAME group (n = 6) received inhaled NO (40 ppm) and L-NAME for the last 2 hours. The control group (n = 5) received only saline without LPS. Hemodynamic data and blood gases were collected hourly for 3 hours. Results: L-NAME worsened LPS-associated pulmonary hypertension and RV dysfunction as reflected by decreased RV ejection fraction. Inhaled nitric oxide significantly decreased pulmonary hypertension and improved RV ejection fraction and stroke work index. There were no adverse systemic effects. Conclusions: Inhaled nitric oxide reverses pulmonary hypertension seen with L-NAME treatment during endotoxemia and may be a useful adjunct to NOS inhibition in the treatment of septic shock.

Original languageEnglish (US)
Pages (from-to)641-646
Number of pages6
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume41
Issue number4
DOIs
StatePublished - Oct 1 1996

Keywords

  • Cardiopulmonary
  • Endotoxemia
  • Inhaled nitric oxide
  • N-nitro-L-arginine methyl ester
  • Nitric oxide
  • Nitric oxide synthase
  • Pulmonary hypertension
  • Sepsis

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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