Adenosine has been postulated to mediate the increase in coronary blood flo
w when myocardial oxygen consumption is increased. The aim of this study wa
s to evaluate the role of adenosine when myocardial oxygen consumption was
augmented by cardiac paired-pulse stimulation without the use of catecholam
ines. In 10 anesthetized closed-chest dogs, coronary blood flow was measure
d in the left circumflex coronary artery, and myocardial oxygen consumption
was calculated using the arteriovenous oxygen difference. Cardiac intersti
tial adenosine concentration was estimated from coronary venous and arteria
l plasma adenosine measurements using a previously described multicompartme
ntal, axially distributed mathematical model. Paired stimulation increased
heart rate from 55 to 120 beats/min, increased myocardial oxygen consumptio
n 104%, and increased coronary blood flow 92%, but the estimated interstiti
al adenosine concentration remained below the threshold for coronary vasodi
lation. After adenosine-receptor blockade with 8-phenyltheophylline (8-PT),
coronary blood flow and myocardial oxygen consumption were not significant
ly different from control values. Paired-pulse pacing during adenosine-rece
ptor blockade resulted in increases in myocardial oxygen consumption and co
ronary blood flow similar to the response before 8-PT. Coronary venous and
estimated interstitial adenosine concentration did not increase to overcome
the adenosine blockade by 8-PT. These results demonstrate that adenosine i
s not required for the local metabolic control of coronary blood flow durin
g pacing-induced increases in myocardial oxygen consumption.