Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

J Vasc Res. 2017;54(2):109-121. doi: 10.1159/000464262. Epub 2017 Apr 26.

Abstract

Background: Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions.

Methods: In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood.

Results: During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables.

Conclusions: During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function.

Keywords: Gastric microcirculation; Hemorrhagic shock; Iloprost; Intestinal barrier function; Nitroglycerin; Sucrose absorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Disease Models, Animal
  • Dogs
  • Female
  • Gastric Absorption / drug effects*
  • Gastric Mucosa / blood supply
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Iloprost / administration & dosage*
  • Microcirculation / drug effects*
  • Nitroglycerin / administration & dosage*
  • Oxygen / blood
  • Oxyhemoglobins / metabolism
  • Permeability
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / drug therapy*
  • Shock, Hemorrhagic / physiopathology
  • Sucrose / blood
  • Time Factors
  • Vasodilator Agents / administration & dosage*

Substances

  • Oxyhemoglobins
  • Vasodilator Agents
  • Sucrose
  • Nitroglycerin
  • Iloprost
  • Oxygen