Selective inhibition of inducible nitric oxide synthase maintains haemodynamic stability without untoward consequences for hepatic function or morphology

Eur J Surg. 1999 Dec;165(12):1167-74. doi: 10.1080/110241599750007711.

Abstract

Objective: To examine the effects of the inducible nitric oxide synthase inhibitor aminoethyl-isothiourea (AE-ITU) on haemodynamic measurements, and correlate these with hepatic morphology and function in a porcine model of endotoxaemia.

Design: Experimental study.

Animals: 15 juvenile pigs.

Interventions: Flow probes were placed around the hepatic artery and portal vein. Catheters were introduced into the portal and hepatic veins, pulmonary artery, and aorta. Infusion of AE-ITU was started one hour before that of endotoxin (study group n = 6); thereafter both substances were infused simultaneously until the end of the study (6 hours). The controls (n = 9) had endotoxin alone.

Main outcome measures: Hepatic morphology assessed by light and electron microscopy; and hepatic integrity and function by transaminase activities and oxygen consumption. Systemic, pulmonary, and hepatic blood flow and pressure.

Results: AE-ITU maintained systemic blood pressure (p < 0.05 compared with controls) without causing pulmonary hypertension. Neither hepatic morphology nor function were adversely influenced.

Conclusion: In endotoxaemia AE-ITU has a favourable haemodynamic profile which is achieved without impairment of hepatic function or morphology.

MeSH terms

  • Animals
  • Blood Pressure
  • Cardiac Output
  • Endotoxemia / pathology
  • Endotoxemia / physiopathology*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Hemodynamics* / drug effects
  • Liver / drug effects
  • Liver / physiopathology*
  • Liver / ultrastructure
  • Liver Circulation / drug effects
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / physiology
  • Nitric Oxide Synthase Type II
  • Oxygen Consumption
  • Swine
  • beta-Aminoethyl Isothiourea / pharmacology*

Substances

  • Enzyme Inhibitors
  • beta-Aminoethyl Isothiourea
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II