Dual cardiac microdialysis to assess drug-induced changes in interstitial purine metabolites: adenosine deaminase inhibition versus adenosine kinase inhibition

Cardiovascular Research
S A MantheiD G Van Wylen

Abstract

The purpose of this study was: 1) to evaluate a dual microdialysis technique coupled with local drug administration in the regionally ischemic rabbit heart, and; 2) to assess the ischemia-induced changes in interstitial fluid (ISF) adenosine during inhibition of adenosine deaminase or adenosine kinase. Two microdialysis probes were implanted parallel to each other and separated by 5 mm in myocardium perfused by a branch of the left coronary artery. Probes were used to sample myocardial ISF and to deliver drugs locally to the myocardium; purine metabolite concentrations in the collected dialysate were used as indices of ISF levels. Three groups of pentobarbital-anesthetized rabbits were studied. In a control group (n = 6), both probes were perfused with Krebs-Henseleit buffer. In the second and third groups, one probe was perfused with buffer, whereas the other probe was perfused with buffer containing 1 mM erythro-2-(2-hydroxy-3-nonyl)adenine (EHNA) (n = 5), an adenosine deaminase inhibitor, or 10 microM iodotubercidin (n = 9), an adenosine kinase inhibitor. All animals were exposed to 30 min of regional myocardial ischemia followed by 60 min of reperfusion. In the control group, similar increases in dialysate purine metabolite...Continue Reading

Citations

Mar 25, 2000·Journal of Molecular and Cellular Cardiology·X BianH F Downey
Dec 24, 2003·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Guro ValenJarle Vaage
Dec 8, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Miranda FongYongge Liu
Dec 16, 2011·Drug and Chemical Toxicology·Sule KalkanYesim Tuncok
May 7, 2002·The Annals of Otology, Rhinology, and Laryngology·Keiji TabuchiJun Kusakari
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