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.