Maintenance of cAMP in non-heart-beating donor lungs reduces ischemia-reperfusion injury. Academic Article uri icon

Overview

abstract

  • Studies suggest that pulmonary vascular ischemia-reperfusion injury (IRI) can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, assessed by capillary filtration coeficient (Kfc), in lungs retrieved from non-heart-beating donors (NHBDs) and reperfused with the addition of the beta(2)-adrenergic receptor agonist isoproterenol (iso), and rolipram (roli), a phosphodiesterase (type IV) inhibitor. Using an in situ isolated perfused lung model, lungs were retrieved from NHBD rats at varying intervals after death and either ventilated with O(2) or not ventilated. The lungs were reperfused with Earle's solution with or without a combination of iso (10 microM) and roli (2 microM). Kfc, lung viability, and pulmonary hemodynamics were measured. Lung tissue levels of adenine nucleotides and cAMP were measured by HPLC. Combined iso and roli (iso/roli) reperfusion decreased Kfc significantly (p < 0.05) compared with non-iso/roli-reperfused groups after 2 h of postmortem ischemia. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso/roli-reperfused (r = 0.89) and iso/roli-reperfused (r = 0.97) lungs. cAMP levels correlated with Kfc (r = 0.93) in iso/roli-reperfused lungs. Pharmacologic augmentation of tissue TAN and cAMP levels might ameliorate the increased capillary permeability observed in lungs retrieved from NHBDs.

publication date

  • June 1, 2001

Research

keywords

  • Cyclic AMP
  • Lung
  • Lung Transplantation
  • Reperfusion Injury
  • Tissue Donors

Identity

Scopus Document Identifier

  • 0034954273

Digital Object Identifier (DOI)

  • 10.1164/ajrccm.163.7.9911060

PubMed ID

  • 11401888

Additional Document Info

volume

  • 163

issue

  • 7