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Updated: Sep 21, 2026
Measurement of Antibody Effects on Cellular Function of Isolated Cardiomyocytes
Published on: March 8, 2013
A1-receptor blockade: a novel approach for assessing myocardial viability in chronic ischemic cardiomyopathy
D Elizabeth Le1, Robert A Pelberg, Howard Leong-Poi
1Cardiovascular Imaging Center, the Cardiovascular Division, University of Virginia School of Medicine, Charlottesville 22908, USA.
Insights
Adenosine contributes to myocardial depression in chronic coronary stenosis (CS) by activating the A(1) receptor. Blocking this receptor with aminophylline or a selective antagonist improved heart function, suggesting a new diagnostic approach.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Diminished myocardial function can occur in chronic coronary stenosis (CS) despite normal resting blood flow.
- Adenosine's role in this myocardial depression, particularly via A(1) receptor activation, is hypothesized.
Purpose of the Study:
- To investigate the role of adenosine in myocardial depression associated with chronic coronary stenosis.
- To test the hypothesis that A(1) adenosine receptor activation contributes to this dysfunction.
Main Methods:
- A canine model of chronic CS was created using ameroid constrictors.
- Aminophylline (nonselective adenosine antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (selective A(1) antagonist) were administered.
- Echocardiography, hemodynamics, and myocardial blood flow measurements were performed before and after drug administration.
Main Results:
- Neither drug affected control animals.
- In CS animals, both drugs significantly increased regional percent wall thickening and decreased end-systolic wall stress.
- These improvements were not explained by changes in myocardial blood flow or systemic hemodynamics.
Conclusions:
- Adenosine significantly contributes to myocardial dysfunction in chronic ischemia through A(1) receptor activation.
- Aminophylline or selective A(1) antagonists may be useful for detecting viable myocardium in severe chronic ischemic heart disease, potentially offering a safer alternative to dobutamine.
Abstract:
Diminished myocardial function can be seen in chronic coronary stenosis (CS) even in the presence of normal resting myocardial blood flow. We hypothesized that adenosine contributes to myocardial depression in this setting, predominantly through activation of the A(1) adenosine receptor. To test this hypothesis we used aminophylline, a nonselective adenosine receptor antagonist, and 8-cyclopentyl 1,3 dipropylxanthine, a selective A(1) adenosine receptor antagonist, in a canine model of chronic CS. Chronic CS was produced by placement of ameroid constrictors on the left anterior descending and left circumflex coronary arteries in 17 adult mongrel dogs, which resulted in severe left ventricular dysfunction 6 weeks later. Eight dogs without ameroid placement were used as controls (C). Closed-chest echocardiographic short-axis images at the low midpapillary level, hemodynamics, and radiolabeled microsphere-derived myocardial blood flow were obtained before and immediately after injection of either 5 mg/kg(-1) of aminophylline (7 left ventricular dysfunction and 4 C dogs) or 1 mg/kg(-1) of 8-cyclopentyl 1,3-dipropylxanthine (10 left ventricular dysfunction and 4 C dogs). Both 8-cyclopentyl 1,3-dipropylxanthine and aminophylline had no effect in C animals but resulted in a significant transient increase in regional percent wall thickening (P <.05) with a concomitant decrease in end-systolic wall stress (P <.05) in CS animals. There was no change in transmural myocardial blood flow or systemic hemodynamics to explain these results. Thus, adenosine plays a significant role in myocardial dysfunction in chronic ischemia by activation of the A(1) receptor. Aminophylline or a selective A(1) adenosine receptor antagonist can be used to detect viable myocardium and may be safer than dobutamine in severe chronic ischemic heart disease.
