Inhaled prostacyclin reduces cardiopulmonary bypass-induced pulmonary endothelial dysfunction via increased cyclic adenosine monophosphate levels

J Thorac Cardiovasc Surg. 2004 Jul;128(1):109-16. doi: 10.1016/j.jtcvs.2003.09.056.

Abstract

Objective: Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. This study was designed to demonstrate that inhaled prostacyclin, a selective pulmonary vasodilator prostaglandin, prevents pulmonary arterial endothelial dysfunction induced by cardiopulmonary bypass.

Methods: Three groups of Landrace swine were compared: control without cardiopulmonary bypass (control group); 90 minutes of normothermic cardiopulmonary bypass (bypass group); 90 minutes of cardiopulmonary bypass and treated with prostacyclin during cardiopulmonary bypass (continuous nebulization with continuous positive airway pressure until the end of the cardiopulmonary bypass; prostacyclin group). After 60 minutes of reperfusion, swine were put to death and pulmonary arteries harvested. After contraction to phenylephrine, endothelium-dependent relaxation to bradykinin and acetylcholine was studied in standard organ chamber experiments. The pulmonary artery intravascular cyclic adenosine monophosphate content was compared between the 3 groups (post-cardiopulmonary bypass).

Results: There was a statistically significant improvement of the endothelium-dependent relaxation to bradykinin in the prostacyclin group when compared with the bypass group (P <.05). There was no statistically significant difference for endothelium-dependent relaxation to acetylcholine (P >.05) between the prostacyclin and the bypass groups. There was a statistically significant decrease in the cyclic adenosine monophosphate content and a statistically significant increase of the mean pulmonary artery pressure in the bypass group only (P <.05).

Conclusion: Prophylactic use of inhaled prostacyclin has a favorable impact on the pulmonary endothelial dysfunction induced by cardiopulmonary bypass associated with preservation of pulmonary intravascular cyclic adenosine monophosphate content and the pulmonary vascular tone.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / administration & dosage
  • Adenosine Monophosphate / metabolism*
  • Administration, Inhalation
  • Animals
  • Antihypertensive Agents / administration & dosage*
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Cardiopulmonary Bypass / adverse effects*
  • Cardiovascular Agents / administration & dosage
  • Cyclic AMP / blood*
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Epoprostenol / administration & dosage*
  • Female
  • Indoles / administration & dosage
  • Lung / blood supply*
  • Lung / metabolism*
  • Lung Diseases / etiology*
  • Lung Diseases / metabolism
  • Lung Diseases / physiopathology
  • Lung Diseases / prevention & control*
  • Male
  • Models, Cardiovascular
  • Phenylephrine / administration & dosage
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / physiopathology
  • Pulmonary Wedge Pressure / drug effects
  • Swine
  • Vascular Resistance / drug effects
  • Vasoconstrictor Agents / administration & dosage
  • Vasodilation / drug effects
  • Vasodilator Agents / administration & dosage

Substances

  • Antihypertensive Agents
  • Antioxidants
  • Biomarkers
  • Cardiovascular Agents
  • Indoles
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Phenylephrine
  • indolylheptylamine
  • Adenosine Monophosphate
  • Epoprostenol
  • Cyclic AMP
  • Acetylcholine