Reduction of oedema formation after preconditioning with dopamine in an isolated rat lung model is mediated by adrenergic receptors

Ann Transplant. Jul-Sep 2011;16(3):97-107. doi: 10.12659/aot.882001.

Abstract

Background: Donor treatment with dopamine (DA) is an effective modality to improve organ quality by reduction of hypothermic, ischemic and reperfusion (I/R) injury. It is unknown by which mechanism DA reduces oedema formation and inflammation. Therefore we tested the first time in an isolated rat lung model if dopaminergic or adrenergic receptors are involved.

Material/methods: Rats were treated for 1 hr with NaCl, DA or simultaneously with DA alpha- beta- D1- or D2-receptor blockers. Thereafter lungs were explanted, flushed with Perfadex-solution and stored at 4°C. Peak inspiratory pressure (PIP), pulmonary arterial pressure (PAP) and lung weight were measured during reperfusion of 3 hrs. Inflammatory mediators and the expression of adhesion molecules were measured after perfusion.

Results: Up to 6 hours of hypothermia did not influence oedema formation or PIP and PAP during reperfusion time. However, hypothermia after 8 hrs significantly increased PIP, PAP and pulmonary oedema in NaCl, alpha- and beta-blocker treated lungs, but significantly not in DA, D1- or D2-blocker treated lungs. Perfusion and ventilation alone induced a strong upregulation of cytokine-induced neutrophil chemoattractant-1 and adhesion molecules in untreated, alpha- and beta-blocker treated lungs, while in DA, D1- and D2-blocker treated lungs significant lower levels were found.

Conclusions: Our study suggests that dopamine mediated protective effects on I/R damage and inflammation in donor lungs are most likely mediated via adrenergic receptors. These findings are highly relevant because new strategies for organ preservation are necessary in terms of long donation waiting lists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / administration & dosage
  • Animals
  • Blood Pressure
  • Chemokine CXCL1 / metabolism
  • Disease Models, Animal
  • Dopamine / administration & dosage*
  • In Vitro Techniques
  • Ischemic Preconditioning / methods*
  • Lung / drug effects
  • Lung / metabolism
  • Lung Injury / physiopathology
  • Lung Injury / prevention & control
  • Lung Transplantation
  • Organ Preservation / methods
  • Pulmonary Edema / metabolism
  • Pulmonary Edema / prevention & control*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control

Substances

  • Adrenergic Antagonists
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • Receptors, Adrenergic
  • Dopamine