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 Citations (Scopus)

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 1996
Externally publishedYes

Fingerprint

Septic Shock
Nitric Oxide
Swine
Lipopolysaccharides
Pulmonary Hypertension
Nitric Oxide Synthase
Right Ventricular Dysfunction
Endotoxemia
Stroke Volume
Women's Rights
Positive-Pressure Respiration
Cardiac Output
arginine methyl ester
Sepsis
Therapeutics
Gases
Hemodynamics
Stroke
Escherichia coli
Control Groups

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

Cite this

Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock. / Offner, Patrick J.; Ogura, Hiroshi; Jordan, Bryan S.; Pruitt, Basil A; Cioffi, William G.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 41, No. 4, 10.1996, p. 641-646.

Research output: Contribution to journalArticle

Offner, Patrick J. ; Ogura, Hiroshi ; Jordan, Bryan S. ; Pruitt, Basil A ; Cioffi, William G. / Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock. In: Journal of Trauma - Injury, Infection and Critical Care. 1996 ; Vol. 41, No. 4. pp. 641-646.
@article{3eb71b7352554277b047d8c942799a2d,
title = "Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock",
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.",
keywords = "Cardiopulmonary, Endotoxemia, Inhaled nitric oxide, N-nitro-L-arginine methyl ester, Nitric oxide, Nitric oxide synthase, Pulmonary hypertension, Sepsis",
author = "Offner, {Patrick J.} and Hiroshi Ogura and Jordan, {Bryan S.} and Pruitt, {Basil A} and Cioffi, {William G.}",
year = "1996",
month = "10",
doi = "10.1097/00005373-199610000-00008",
language = "English (US)",
volume = "41",
pages = "641--646",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock

AU - Offner, Patrick J.

AU - Ogura, Hiroshi

AU - Jordan, Bryan S.

AU - Pruitt, Basil A

AU - Cioffi, William G.

PY - 1996/10

Y1 - 1996/10

N2 - 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.

AB - 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.

KW - Cardiopulmonary

KW - Endotoxemia

KW - Inhaled nitric oxide

KW - N-nitro-L-arginine methyl ester

KW - Nitric oxide

KW - Nitric oxide synthase

KW - Pulmonary hypertension

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=0029858711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029858711&partnerID=8YFLogxK

U2 - 10.1097/00005373-199610000-00008

DO - 10.1097/00005373-199610000-00008

M3 - Article

C2 - 8858022

AN - SCOPUS:0029858711

VL - 41

SP - 641

EP - 646

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 4

ER -