Inosine, not adenosine, initiates endothelial glycocalyx degradation in cardiac ischemia and hypoxia.

Abstract

Ischemia/reperfusion and hypoxia/reoxygenation of the heart both induce shedding of the coronary endothelial glycocalyx. The processes leading from an oxygen deficit to shedding are unknown. An involvement of resident perivascular cardiac mast cells has been proposed. We hypothesized that either adenosine or inosine or both, generated by nucleotide catabolism, attain the concentrations in the interstitial space sufficient to stimulate A3 receptors of mast cells during both myocardial ischemia/reperfusion and hypoxia/reoxygenation. Isolated hearts of guinea pigs were subjected to either normoxic perfusion (hemoglobin-free Krebs-Henseleit buffer equilibrated with 95% oxygen), 20 minutes hypoxic perfusion (buffer equilibrated with 21% oxygen) followed by 20 minutes reoxygenation, or 20 minutes stopped-flow ischemia followed by 20 minutes normoxic reperfusion (n = 7 each). Coronary venous effluent was collected separately from so-called transudate, a mixture of interstitial fluid and lymphatic fluid appearing on the epicardial surface. Adenosine and inosine were determined in both fluid compartments using high-performance liquid chromatography. Damage to the glycocalyx was evident after ischemia/reperfusion and hypoxia/reoxygenation. Adenosine concentrations rose to a level of 1 μM in coronary effluent during hypoxic perfusion, but remained one order of magnitude lower in the interstitial fluid. There was only a small rise in the level during postischemic perfusion. In contrast, inosine peaked at over 10 μM in interstitial fluid during hypoxia and also during reperfusion, while effluent levels remained relatively unchanged at lower levels. We conclude that only inosine attains levels in the interstitial fluid of hypoxic and postischemic hearts that are sufficient to explain the activation of mast cells via stimulation of A3-type receptors.

• Authors: B F Becker, J Fischer, H Hartmann, C C Chen, C P Sommerhoff, J Tschoep, P C Conzen, T Annecke
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 30 Issue 12 Pg. 1161-7 (Dec 2011) ISSN: 1532-2335 [Electronic] United States
• PMID: 22132971 (Publication Type: Journal Article)

Chemical References

• Inosine
• Adenosine

Topics

• Adenosine (metabolism)
• Animals
• Endothelium (metabolism, pathology)
• Glycocalyx (metabolism)
• Guinea Pigs
• Hypoxia (complications, metabolism, pathology)
• In Vitro Techniques
• Inosine (metabolism)
• Myocardial Ischemia (complications, metabolism, pathology)