Changes in cardiac interstitial fluid adenosine concentration during hypoxia, ischemia, and dipyridamole in the intact dog heart

• Published in: Japanese Journal of Pharmacology Vol. 52; no. suppl.2; p. 88
• Main Authors: Van Wylen, David G.L., Dorheim, Tracy A., Wang, Tao, Sodhi, Jitendra, Laslev, Robert D., Mentzer, Robert M.
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1990
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)32960-9

The purpose of these studies was to use a new technique, cardiac microdialysis, to determine the changes in cardiac interstitial fluid (ISF) adenosine (ADO) and ADO metabolite levels. Cardiac microdialysis probes were implanted in the left ventricular myocardium of anesthetized dogs and perfused at 2.0 μl/min with Krebs-Henseleit buffer. Animals were subjected to either hypoxia (P_a O_2 =32.1 ± 1.0 mmHg; n=12), regional myocardial ischemia (occlusion o f the left anterior descending coronary artery; n=7) or dipyridamole infusion (8μg/kg/min iv; n=10). Basal ISF ADO was approximately 1 μM. Hypoxia resulted in a 60% increase in ISF ADO levels along with a 3-fold increase in coronary blood flow (CBF). During regional myocardial ischemia, ISF ADO increased 6-fold by 15 minutes after occlusion and thereafter gradually declined; inosine, hypoxanthine, and xanthine comprised greater than 95% of the purine metabolites in the ISF after 20 minutes of ischemia. Dipyridamole, which caused a 4-fold increase in CBF, was associated with a 2.6-fold increase in ISF ADO. These data demonstrate that ISF ADO increases during decreased myocardial oxygen supply or inhibition of ADO uptake.