Adenosine kinetics in the canine coronary circulation.
Kroll, Keith, and David W. Stepp.
Center for Bioengineering and Department of Physiology and
Biophysics, University of Washington, Seattle, WA 98195
APStracts 2:0408H, 1995.
Adenosine kinetics in the coronary circulation were investigated in
anesthetized closed-chest dogs by analysis of multiple indicator
dilution experiments. During simultaneous intracoronary bolus
injections of [125I]-albumin, [14C]-sucrose and [3H]-adenosine,
dilution curves were measured by automated sampling of coronary
venous blood, using high pressure liquid chromatography and isotope
detection techniques. Under control conditions, only 1% of the
injected [3H]-adenosine was detected in coronary venous samples,
compared to the reference tracer, [14C]-sucrose, and the peak of the
adenosine dilution curve preceded those of the reference tracers by
2-4 seconds. Optimized model fits to the control adenosine curves
required the combination of high ratios of the capillary endothelial
cell membrane permeability-surface area product to flow (PSecl/F =
5.3), and endothelial cell consumption capacity to flow (Gec/F = 23),
in addition to a broad heterogeneity of flow. Dilution curves were
measured under control conditions, during increased coronary flow
(nitroglycerin), inhibition of the enzyme adenosine kinase
(iodotubercidin), and blockade of membrane adenosine transport
(dipyridamole). Reliability of the parameter estimates was confirmed
using residual analysis,sensitivity function analysis and Monte Carlo
simulation techniques. Accuracy of the model was confirmed in
separate experiments in which nontracer adenosine was infused into
the coronary artery and the model prediction of coronary venous
adenosine concentrations was compared with measured values. Using
published measurements of coronary blood flow and arterial and
coronary venous plasma adenosine concentrations in open-chest dogs,
the estimated in vivo interstitial adenosine concentration is 100-220
nM.
Received 21 July 1995; accepted in final form 5 September 1995.
APS Manuscript Number H691-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.