Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Circulation Research. 1992;71:590-604

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kroll, K.
Right arrow Articles by Sweet, I. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kroll, K.
Right arrow Articles by Sweet, I. R.

Circulation Research, Vol 71, 590-604, Copyright © 1992 by American Heart Association

ARTICLES

Comprehensive model of transport and metabolism of adenosine and S- adenosylhomocysteine in the guinea pig heart

K Kroll, A Deussen and IR Sweet
Center for Bioengineering, University of Washington, Seattle 98195.

Regulation of blood flow and mitochondrial respiration in the heart would be clarified by improved knowledge of interstitial concentrations and cellular production rates of adenosine; however, these variables cannot be measured directly. To interpret indexes that are available, a comprehensive mathematical model was developed, based on a large body of experimental data. The model describes most of the important pathways of capillary-tissue transport and cellular metabolism of adenosine in the guinea pig heart. It includes capillary flow, solute transport between tissue regions, nonlinear enzyme kinetics for adenosine kinase and adenosine deaminase, and reversible biunireactant kinetics for S-adenosylhomocysteine hydrolase in cardiomyocytes and endothelial cells, intracellular production of adenosine via AMP hydrolysis and transmethylation, and extracellular production of adenosine. A single set of parameter values for the model was obtained in the first stage of the analysis by taking certain values directly from published sources, other values were subject to specific constraints, and other values were determined by parameter optimization. The effects of flow and endothelial metabolism on the relation between interstitial and venous adenosine concentrations were determined. The relation between myocardial adenosine production rate and S-adenosylhomocysteine accumulation in the presence of excess homocysteine was estimated. In the second stage of the analysis, the model was used to investigate the mechanism of myocardial adenosine production, without changing the parameter values. Cellular adenosine production rates were estimated by fitting measurements of venous adenosine release obtained during altered energetic conditions in experiments by different investigators. The original results showed a dissociation between measurements of cytosolic AMP concentrations and venous adenosine release. It is concluded that 1) it is essential to account for the effect of flow on interstitial and venous adenosine concentrations, since decreased flow may produce effects outwardly resembling inhibition of the enzyme 5'-nucleotidase, 2) adenosine concentrations in epicardial transudate are not in equilibrium with interstitial fluid, and 3) the rate of cellular adenosine production increases monotonically with free cytosolic concentrations of AMP during a variety of alterations in energy balance of the guinea pig heart.


This article has been cited by other articles:


Home page
 Exp PhysiolHome page
M. E. Reichelt, L. Willems, J. N. Peart, K. J. Ashton, G. P. Matherne, M. R. Blackburn, and J. P. Headrick
Heart/Cardiac Muscle: Modulation of ischaemic contracture in mouse hearts: a 'supraphysiological' response to adenosine
Exp Physiol, January 1, 2007; 92(1): 175 - 185.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
N. P. Riksen, G. A. Rongen, H. J. Blom, F. G.M. Russel, G. H.J. Boers, and P. Smits
Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia
Cardiovasc Res, August 1, 2003; 59(2): 271 - 276.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. D. Tune, K. N. Richmond, M. W. Gorman, and E. O. Feigl
KATP+ channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation
Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H868 - H875.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Mattig and A. Deussen
Significance of adenosine metabolism of coronary smooth muscle cells
Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H117 - H124.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. W. Gorman, J. D. Tune, K. N. Richmond, and E. O. Feigl
Feedforward sympathetic coronary vasodilation in exercising dogs
J Appl Physiol, November 1, 2000; 89(5): 1892 - 1902.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
K. N. Richmond, J. D. Tune, M. W. Gorman, and E. O. Feigl
Role of KATP+ channels and adenosine in the control of coronary blood flow during exercise
J Appl Physiol, August 1, 2000; 89(2): 529 - 536.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. D. Tune, K. N. Richmond, M. W. Gorman, and E. O. Feigl
Role of Nitric Oxide and Adenosine in Control of Coronary Blood Flow in Exercising Dogs
Circulation, June 27, 2000; 101(25): 2942 - 2948.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. D. Tune, K. N. Richmond, M. W. Gorman, R. A. Olsson, and E. O. Feigl
Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise
Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H74 - H84.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. N. Richmond, J. D. Tune, M. W. Gorman, and E. O. Feigl
Role of K+ATP channels in local metabolic coronary vasodilation
Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2115 - H2123.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Yada, K. N. Richmond, R. van Bibber, K. Kroll, and E. O. Feigl
Role of adenosine in local metabolic coronary vasodilation
Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1425 - H1433.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
A. Deussen, M. Stappert, S. Schafer, and M. Kelm
Quantification of Extracellular and Intracellular Adenosine Production : Understanding the Transmembranous Concentration Gradient
Circulation, April 20, 1999; 99(15): 2041 - 2047.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. C. Shryock, S. Snowdy, P. G. Baraldi, B. Cacciari, G. Spalluto, A. Monopoli, E. Ongini, S. P. Baker, and L. Belardinelli
A2A-Adenosine Receptor Reserve for Coronary Vasodilation
Circulation, August 18, 1998; 98(7): 711 - 718.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
U. K. M. Decking, G. Schlieper, K. Kroll, and J. Schrader
Hypoxia-Induced Inhibition of Adenosine Kinase Potentiates Cardiac Adenosine Release
Circ. Res., August 19, 1997; 81(2): 154 - 164.
[Abstract] [Full Text]

Home page
 Circ. Res.Home page
D. W. Stepp, R. Van Bibber, K. Kroll, and E. O. Feigl
Quantitative Relation Between Interstitial Adenosine Concentration and Coronary Blood Flow
Circ. Res., September 1, 1996; 79(3): 601 - 610.
[Abstract] [Full Text]


Circulation Research Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 1992 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.