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Estimates of left ventricular interstitial fluid adenosine during catecholamine stimulation
J M Gidday1, H E Hill, R Rubio
1Department of Physiology, University of Virginia School of Medicine, Charlottesville 22908.
Insights
Interstitial fluid adenosine (Ado) concentrations in the heart directly influence coronary blood flow (CBF). This study validates a new method for measuring Ado, confirming its role in regulating blood flow during catecholamine stimulation.
Area of Science:
- Cardiovascular Physiology
- Biochemical Regulation
- Myocardial Metabolism
Background:
- The relationship between myocardial interstitial fluid (ISF) adenosine (Ado) and coronary blood flow (CBF) regulation is debated.
- Previous methods for measuring ISF Ado rely on assumptions that may not be valid.
Purpose of the Study:
- To validate a novel epicardial chamber (EC) method for estimating ISF Ado concentrations.
- To investigate the role of ISF Ado in mediating coronary hyperemia during catecholamine stimulation.
Main Methods:
- Utilized an epicardial chamber (EC) on the left ventricular epicardium of anesthetized dogs.
- Measured endogenous adenosine accumulation in the EC buffer to estimate ISF Ado.
- Administered intravenous catecholamines to assess effects on Ado concentrations and influx kinetics.
Main Results:
- The EC method provided direct estimates of steady-state ISF Ado concentrations (75-125 nM) within 4 minutes.
- Catecholamine infusions doubled steady-state EC Ado concentrations without altering Ado influx.
- Demonstrated ISF Ado accumulation and its role in catecholamine-induced hyperemia.
Conclusions:
- The EC technique offers a more direct estimation of myocardial interstitial fluid adenosine concentrations.
- Interstitial fluid adenosine plays a significant role in mediating the increased coronary blood flow associated with myocardial catecholamine stimulation.
Abstract:
The hypothesis that changes in myocardial interstitial fluid (ISF) adenosine (Ado) concentrations couple coronary blood flow (CBF) with myocardial oxygen need is still controversial. Measurements of Ado in cardiac tissue, coronary sinus plasma, and pericardial infusates have commonly been used as indexes of ISF Ado, but recent studies have highlighted the potential invalidity of many of the assumptions underlying these sampling methods. With the use of an epicardial chamber (EC) to contain a small volume of buffer on the undisturbed left ventricular epicardium of anesthetized open-chest dogs, estimates of ISF Ado can be obtained without invoking these assumptions. In experiments designed to validate our method and investigate the role of Ado in the regulation of CBF during myocardial catecholamine stimulation, we found that endogenous Ado accumulated in the EC exponentially and attained constant steady-state concentrations, ranging from 75 to 125 nM, within 4 min. Intravenous infusions of two catecholamines increased steady-state EC Ado concentrations twofold, but did not affect Ado influx kinetics. We conclude that the EC technique yields more direct estimates of steady-state ISF Ado concentrations than previously available and that ISF Ado is involved in the mediation of the hyperemia accompanying myocardial catecholamine stimulation.