Effect of aerosolized prostacyclin and inhaled nitric oxide on experimental hypoxic pulmonary hypertension

Intensive Care Med. 1999 Oct;25(10):1147-54. doi: 10.1007/s001340051027.

Abstract

Objective: To compare the effect of different concentrations of inhaled nitric oxide and doses of nebulized prostacyclin on hypoxia-induced pulmonary hypertension in pigs.

Design: Prospective, controlled animal study.

Setting: Animal research facilities of an university hospital.

Interventions: After reducing the fraction of inspired oxygen (FIO(2)) from 1.0 to 0.1, two groups of five pigs each were submitted to inhalation of three concentrations of nitric oxide (5, 10 and 20 ppm) or three doses of prostacyclin (2.5, 5, 10 ng x kg(-1) x min(-1)).

Results: All doses of prostacyclin and concentrations of nitric oxide resulted in a decrease in mean pulmonary arterial pressure and pulmonary vascular resistance when compared to hypoxic ventilation (p < 0.001) which was independent of the dose or concentration of either drug used. While inhalation of nitric oxide caused a reduction in mean pulmonary arterial pressure back to values obtained during ventilation with FIO(2) 1.0, values achieved with prostacyclin were still significantly higher when compared to measurements prior to the initiation of hypoxic ventilation. However, direct comparison of the effect of 20 ppm nitric oxide and 10 ng x kg(-1) x min(-1) prostacyclin on mean pulmonary arterial pressure revealed no differences between the drugs. All other hemodynamic and gas exchange parameters remained stable throughout the study.

Conclusions: Inhalation of clinically used concentrations of nitric oxide and doses of prostacyclin can decrease elevated pulmonary arterial pressure in an animal model of hypoxic pulmonary vasoconstriction without impairing systemic hemodynamics or gas exchange.

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Aerosols
  • Animals
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / pharmacology
  • Blood Gas Analysis
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical
  • Drug Monitoring
  • Epoprostenol / administration & dosage*
  • Epoprostenol / pharmacology
  • Female
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / physiopathology
  • Hypoxia / blood
  • Hypoxia / complications*
  • Nitric Oxide / administration & dosage*
  • Nitric Oxide / pharmacology
  • Prospective Studies
  • Pulmonary Gas Exchange / drug effects
  • Pulmonary Wedge Pressure / drug effects
  • Respiration, Artificial / methods
  • Swine
  • Vascular Resistance / drug effects
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / pharmacology

Substances

  • Aerosols
  • Antihypertensive Agents
  • Vasodilator Agents
  • Nitric Oxide
  • Epoprostenol